CN108070615A - A kind of carrier of regulation and control parathyroid gland PTH secretions and its application - Google Patents

Abstract

Carrier and its application, the carrier the present invention provides a kind of regulation and control parathyroid gland PTH secretions include the PTH promoters of photosensitizing effect and/or specific recognition chief cell, the nucleotide sequence such as SEQ ID NO of the PTH promoters:Shown in 1；The carrier is used to prepare drug and the system for adjusting parathyroid gland is formed with specific wavelength and the blue light of frequency；The present invention identifies parathyroid cells using specificity promoter, and the secretion of parathormone is regulated and controled by specific wavelength and the blue light of frequency, and high space-time, high-precision, specificity is good, and effect is remarkable, has broad application prospects and market value.

Description

A carrier for regulating the secretion of parathyroid gland PTH and its application

technical field

The invention relates to the field of biotechnology, in particular to a carrier for regulating the secretion of parathyroid gland PTH and its application.

Background technique

The parathyroid gland is a very important gland in the endocrine system. The parathyroid hormone (PTH) secreted by it is an important regulator of calcium and phosphorus homeostasis secreted by the parathyroid chief cells. Phosphorus balance and bone metabolism play an important role in the process of homeostasis. PTH participates in the regulation of bone metabolism. By acting on osteoblasts, PTH can promote bone resorption and bring bone calcium into the blood, thereby increasing blood calcium concentration. The whole synthesis and secretion process of PTH is jointly mediated by calcium, vitamin D and growth factors, and the blood calcium concentration is directly related to the PTH concentration. When the parathyroid gland itself undergoes lesions or secondary hyperplasia, neoplasia or even canceration caused by other diseases in the body, the synthesis and secretion of PTH will increase explosively, and the concentration in the blood will increase abnormally; this abnormal increase can promote Bone resorption leads to faster and more severe osteoporosis, greatly increasing the risk of fractures and even paralysis; at the same time, high concentrations of PTH directly cause hypercalcemia, coupled with the release of bone matrix and changes in urine pH often lead to Recurrent urinary calculi lead to a gradual decline in renal function, and even renal failure and uremia. Hypercalcemia caused by PTH accumulation may also harm multiple other systems of the body, such as the cardiac circulatory system, neuromuscular motor system, digestive system and central system, which can lead to abnormal blood sugar, blood lipid metabolism, blood pressure regulation disorders and even neuropsychiatric diseases.

At present, the methods for the treatment of hyperparathyroidism mainly include drug intervention and surgical resection. Drug intervention mainly includes oral phosphorus, estrogen, calcimimetic, active vitamin D, etc. Oral phosphorus can reduce PTH-induced hypercalcemia, but oral phosphorus can in turn cause an increase in PTH, so it is rarely used. Taking estrogen can effectively reduce osteolysis, increase bone mass, and antagonize the bone resorption of PTH. However, estrogen has a wide range of actions and poor specificity, which can easily cause cell proliferation. It has even been reported that long-term use of estrogen can easily cause gynecological tumors and other serious complications. Calcimimetic agents are recently discovered based on the regulation of calcium-related receptors in principal cells. They have the ability to simulate calcium elevation and negative feedback inhibition of PTH secretion. New potential drugs for the treatment of hyperparathyroidism; however, this drug is still in the research and development stage, and there is no Adequate clinical data. In addition, taking active vitamin D in large doses for a long time can inhibit the secretion of PTH, but it often causes symptoms of hyperphosphatemia. In general, the existing drug interventions for hyperparathyroidism have the disadvantages of poor specificity, wide range of action, and easy to cause complications. At present, there is no particularly effective drug intervention method. At present, the commonly used clinical treatment is parathyroidectomy combined with autologous transplantation. Because the transplanted tissue is not innervated by the body, the rhythm of PTH secretion will be disturbed in a short period of time, and the concentration may still be higher than the normal value. However, total parathyroidectomy will lead to sudden hypocalcemia, and autologous parathyroid tissue transplantation is required to maintain a stable blood calcium concentration. The PTH concentration after transplantation is difficult to control, and there is a certain risk of tumorization.

Due to the poor specificity of the commonly used drugs, the effect is not obvious. At present, the main clinical treatment is parathyroidectomy and autologous transplantation. Because the transplanted tissue is not innervated by nerves, the rhythm of PTH secretion will be disturbed in a short period of time, and the concentration may increase. still higher than normal. If a method can be found to specifically inhibit the PTH secretion of parathyroid chief cells, then the parathyroid tissue can be regulated in situ or after transplantation, the abnormal secretion of PTH can be inhibited, and a series of diseases caused by hypercalcemia can be effectively reduced. symptom.

Optogenetic regulation technology is a rapidly developing emerging technology that appeared at the beginning of this century; its principle is to transfer different light-sensitive genes to mammalian cells based on gene therapy, and regulate the activity of specific cell types through light of different wavelengths . At the beginning of the emergence of optogenetic technology, this technology was mainly applied in the field of neuroscience, focusing on the regulation of neuron activity; with the advancement and promotion of technology, this technology was gradually applied to research in other fields, such as: optogenetics Regulation of cardiomyocytes, optogenetics technology regulation of insulin secretion, etc. But so far, there has been no report on the regulation of parathyroid chief cells by optogenetic technology.

In summary, the development of a regulatory vector based on high spatiotemporal selectivity and cell specificity and related technologies for the regulation of endocrine gland cell functions has broad market value and application prospects.

Contents of the invention

In view of the deficiencies in the prior art and actual needs, the present invention provides a carrier for regulating the secretion of parathyroid PTH and its application. The carrier carries a photosensitive gene and a PTH promoter that specifically recognizes the parathyroid gland. The carrier It is used to prepare drugs and form a system to regulate parathyroid glands with blue light of specific frequency and wavelength. The PTH promoter targets and recognizes parathyroid glands, and blue light stimulation of specific frequencies and wavelengths regulates photosensitive genes, achieving high-spatial and high-precision specific regulation The function of parathyroid hormone secretion has broad application prospects and market value.

For reaching this purpose, the present invention adopts following technical scheme:

In one aspect, the present invention provides a vector for regulating PTH secretion of parathyroid glands, said vector comprising a photosensitive gene and/or a PTH promoter that specifically recognizes parathyroid principal cells;

The nucleic acid sequence of the PTH promoter is shown in SEQ ID NO: 1, and the nucleic acid sequence shown in SEQ ID NO: 1 is as follows:

CTGGAGTTCAAAGAAGGGCTGTATTTCTAGGCAGAAACTGAGGTAGTAAGAATCTGGTGTCATAAAGACCTTTGTTGAATTCCATCTTTTCTGCTTTCCAAGCCTAAGTTTCCTCATGTAAAAATGGGGATAAGCACTTAACTTTAGTACTTTAAGTACTAACTTTAAAGGACTGCTGTGAAGATCTAGTGGGATAATATATGTAGTTAGGCATGCAGTTAGTGCTTATCAAATGTTATTATTATAGATTAAGATGCACAAATAAAATATAAGTTAAATAAATTTTAAAATAATTTCACTTTTGAAGCTTTTAAAGTAATTATGTACTAAGAGCATTTTCTCAAATTATTCTTAACACTTCCTTTAAGAAAAGGGCTATATCTGTTTTTTGAAAGATGACCAGAAGTGACATGGATTGGTTGAAAATGGCTTGTAAAGTAAGCCTAACATTTATGATTTATTACCATAAAAACTGTACCAACAGTACGGTTATAACAAATACACTTATTTTTGGGTTTTATTTTCAAGTAAGATAATGACTTTATCATAAACCTTTGAAATCAGTCTTTTTACAGTATAAATTCAGATTCATTAATCCACATAGAATTTTTCTCGATGGTATAATTCTGTATTTGTTAAAAGTCTTTGCATAAGCCCCTTGTCAAGCCAAATGCTGTTTTCCTTTTAGTATCCAATTATCTGAAACTTAAGAAGAGTGTGCACCGCCCAATGGGTGTGTGTATGTGCTGCTTTGAACCTATAGTTGAGATCCAGAGAATTGGGAGTGACATCATCTGTAACAATAAAAGAGCCTCTCTTGGTAAGCAGAAGACCTATATATAAAAGTCACCATTTAAGGGGTCTGCAGTCCAATTCATCAGTTGTCTTTAGTTTACTCAGCATCAGCTACTAACATACCTGAACG；

The photosensitive gene is a gene that can express a cell membrane channel protein that is sensitive to blue light. The photosensitive protein can open a channel under the irradiation of a specific wavelength (such as 470nm), so that cations (sodium ions, calcium ions, etc.) enter the cytoplasm, causing the cell membrane potential to increase. rise, so as to realize the regulation of cell activity. Optogenetic regulation technology is to regulate the activity of specific cell types through different wavelengths of light by transferring different light-sensitive genes into mammalian cells.

In the present invention, after fully studying the prior art for parathyroid regulation, the advantages and disadvantages of each are summarized. In order to avoid the disadvantages of excessive range of drug action, poor specificity, inconspicuous effect and the problem of PTH secretion disorder after surgical resection, creatively select Optogenetic regulation technology, using specific promoters, can specifically recognize the PTH promoter of parathyroid chief cells, identify parathyroid chief cells, and regulate the parathyroid principal cells through blue light irradiation of specific wavelengths and frequencies. PTH secretion achieves the purpose of highly spatiotemporal and precise regulation of parathyroid principal cells.

Preferably, the photosensitive gene is ChR2, the nucleotide sequence of the ChR2 is shown in SEQ ID NO: 2, and the nucleotide sequence shown in the SEQ ID NO: 2 is as follows:

ATGGACTATGGCGGCGCTTTGTCTGCCGTCGGACGCGAACTTTTGTTCGTTACTAATCCTGTGGTGGTGAACGGGTCCGTCCTGGTCCCTGAGGATCAATGTTACTGTGCCGGATGGATTGAATCTCGCGGCACGAACGGCGCTCAGACCGCGTCAAATGTCCTGCAGTGGCTTGCAGCAGGATTCAGCATTTTGCTGCTGATGTTCTATGCCTACCAAACCTGGAAATCTACATGCGGCTGGGAGGAGATCTATGTGTGCGCCATTGAAATGGTTAAGGTGATTCTCGAGTTCTTTTTTGAGTTTAAGAATCCCTCTATGCTCTACCTTGCCACAGGACACCGGGTGCAGTGGCTGCGCTATGCAGAGTGGCTGCTCACTTGTCCTGTCATCCTTATCCGCCTGAGCAACCTCACCGGCCTGAGCAACGACTACAGCAGGAGAACCATGGGACTCCTTGTCTCAGACATCGGGACTATCGTGTGGGGGGCTACCAGCGCCATGGCAACCGGCTATGTTAAAGTCATCTTCTTTTGTCTTGGATTGTGCTATGGCGCGAACACATTTTTTCACGCCGCCAAAGCATATATCGAGGGTTATCATACTGTGCCAAAGGGTCGGTGCCGCCAGGTCGTGACCGGCATGGCATGGCTGTTTTTCGTGAGCTGGGGTATGTTCCCAATTCTCTTCATTTTGGGGCCCGAAGGTTTTGGCGTCCTGAGCGTCTATGGCTCCACCGTAGGTCACACGATTATTGATCTGATGAGTAAAAATTGTTGGGGGTTGTTGGGACACTACCTGCGCGTCCTGATCCACGAGCACATATTGATTCACGGAGATATCCGCAAAACCACCAAACTGAACATCGGCGGAACGGAGATCGAGGTCGAGACTCTCGTCGAAGACGAAGCCGAGGCCGGAGCCGTGCCAGCGGCCGCC；

In the present invention, the ChR2 (Channelrhodopsin-2) encodes a cation channel protein, and after the blue light of 470nm wavelength is illuminated, the cations enter the cell to excite the cell activity; the electrical conductivity and fast kinetic properties of the light-sensing gene ChR2 can not only Realize the induction of neurons to generate action potentials by light; it can also regulate the excitability of the nervous system and the transmission of synapses.

In the second aspect, the present invention provides a recombinant adeno-associated virus obtained by co-transfecting mammalian cells with the vector described in the first aspect, liposomes, and packaging helper plasmids;

Preferably, the liposome comprises calcium phosphate, Lipofectamine 2000 or FnGENE, preferably FnGENE.

Preferably, the mammalian cells are 293FT cells.

Preferably, the packaging helper plasmid includes pAAV-RC and/or pHepler.

In the third aspect, the present invention provides a carrier according to the first aspect for preparing a drug for regulating parathyroid glands.

In the fourth aspect, the present invention provides a medicament comprising the recombinant adeno-associated virus described in the second aspect.

In the fifth aspect, the present invention provides a system comprising the drug as described in the fourth aspect and blue light for regulating parathyroid glands.

Preferably, the blue light has a wavelength of 450-500nm, such as 450nm, 460nm, 470nm, 480nm, 490nm or 500nm, preferably 460-480nm.

Preferably, the frequency of the blue light is 15-25 Hz, such as 15 Hz, 16 Hz, 17 Hz, 18 Hz, 19 Hz, 20 Hz, 21 Hz, 22 Hz, 23 Hz, 24 Hz or 25 Hz, preferably 18-22 Hz.

Preferably, the average intensity of blue light is 8-12mW/mm ² , for example, 8mW/mm ² , 9mW/mm ² , 10mW/mm ² , 11mW/mm ² or 12mW/mm ² , preferably 9- 11 mW/mm ² .

In a sixth aspect, the present invention provides a method for regulating parathyroid glands for non-therapeutic purposes, comprising the following steps:

(1) construct a lentivirus carrying a CMV promoter, a photosensitive gene and a fluorescent gene;

(2) Infecting human parathyroid principal cells with the lentivirus described in step (1), and performing a verification experiment;

(3) using blue light to stimulate the cells infected in step (2), and collecting the conditioned medium to detect changes in PTH;

(4) Constructing the recombinant adeno-associated virus described in the second aspect and infecting the parathyroid glands of rats, stimulating the parathyroid glands with blue light, collecting serum, and detecting changes in PTH concentration, blood calcium and blood phosphorus concentration;

Optionally, after step (3), the method further includes constructing the rat parathyroid gland tissue infected with adeno-associated virus disease according to the second aspect, stimulating the tissue with blue light, and collecting the culture medium to detect the PTH concentration.

Preferably, the stimulation time in step (3) is 20-40 min, such as 20 min, 22 min, 24 min, 25 min, 26 min, 28 min, 30 min, 32 min or 35 min, preferably 25-35 min.

Preferably, the method of infection in step (4) is to inject the virus into rat parathyroid glands, 0.2-0.5 microliters per side, for example, 0.2 microliters, 0.3 microliters, 0.4 microliters or 0.5 microliters.

Preferably, the time point of stimulation in step (4) is 18-22 days after infection, such as 18 days, 19 days, 20 days, 21 days or 22 days.

Preferably, the detection method is ELISA.

First, the inventors used a lentivirus (lenti-CMV-ChETA-eYFP, the promoter is CMV, which belongs to a broad-spectrum promoter and can infect all cells without selectivity) to infect human-derived parathyroid chief cells. It was found that PTH secretion can be effectively and reversibly inhibited at the cellular level. In order to achieve cell selectivity, an adeno-associated virus vector with a PTH promoter was designed, and the parathyroid glands of rats were infected after being packaged into viruses. Its PTH secretion can be inhibited, and its function can be restored. After light stimulation directly in rats, it was found that PTH secretion could be reversibly inhibited, and at the same time, the balance of calcium and phosphorus in the blood was also regulated.

As a preferred technical solution, the present invention provides a method for regulating parathyroid glands, which specifically includes the following steps:

(1) construct a lentivirus carrying a CMV promoter, a photosensitive gene and a fluorescent gene;

(2) Infecting human parathyroid principal cells with the virus described in step (1), and performing verification experiments;

(3) using blue light to stimulate the cells infected in step (2), and collecting the conditioned medium to detect changes in PTH;

(4) Construct the recombinant adeno-associated virus described in the second aspect and inject it into rat parathyroid glands, inject 0.2-0.5 microliters on each side, use the isolated parathyroid gland tissue stimulated by blue light 18-22 days after infection, and collect the culture medium Detect PTH concentration;

(5) Inject the recombinant adeno-associated virus described in step (4) into the parathyroid glands of rats, inject 0.2-0.5 microliters on each side, stimulate the parathyroid glands with blue light 18-22 days after infection, collect serum, detect PTH concentration, Changes in blood calcium and phosphorus concentrations;

Wherein, the wavelength of the blue light in step (3), step (4) and step (5) is 450-500nm, the frequency is 15-25Hz, the average intensity of light is 8-12mW/mm ² , and the time is 20-40min.

Compared with the prior art, the present invention has the following beneficial effects:

The vector provided by the present invention can prepare a recombinant adenovirus and a system for regulating parathyroid glands comprising the recombinant adenovirus and blue light, and can specifically regulate parathyroid chief cells with high spatiotemporal accuracy and regulate the release of PTH; this in vivo The specific PTH regulation system and method can avoid the disadvantages of overly wide drug action range, poor specificity and insignificant effect, and can effectively maintain the balance of serum calcium and phosphorus.

Description of drawings

Fig. 1 is the immunostaining identification diagram of the primary human parathyroid principal cell culture system of Example 2 of the present invention, wherein Fig. 1 (A) is an unstained cell diagram, Fig. 1 (B) is a PTH staining diagram, and Fig. 1 ( C) is the CasR calcium ion receptor staining diagram, Figure 1 (D) is the VDR vitamin D receptor staining diagram;

Figure 2 is a diagram of the staining results of virus-infected cells in Example 2 of the present invention, wherein Figure 2 (A) is a fluorescence image of lentivirus-infected cells with a light-sensitive gene, and Figure 2 (B) is a lentivirus without a light-sensitive gene Fluorescence map of infected cells;

Fig. 3 is the experimental flow chart of embodiment 3 of the present invention, wherein Fig. 3 (A) is the experimental procedure diagram, Fig. 3 (B) is the blue light irradiation cell experiment diagram, Fig. 3 (C) is the blue light irradiation cell schematic diagram;

Fig. 4 is the result figure of embodiment 3 of the present invention, wherein Fig. 4 (A) is the test result before stimulation, Fig. 4 (B) is the test result after 1 hour of stimulation, Fig. 4 (C) is the test result after 6 hours of stimulation;

Fig. 5 is the experiment process figure of embodiment 4 of the present invention, wherein Fig. 5 (A) is the anatomy diagram of rat, Fig. 5 (B) is the schematic diagram of expression virus of parathyroid gland, Fig. 5 (C) is the rat thyroid gland that operation takes out Schematic diagram of paraglandular tissue, Figure 5 (D) blue light irradiation map;

Fig. 6 is the result graph of Example 4 of the present invention, wherein Fig. 6 (A) is a histogram of PTH, Fig. 6 (B) is a histogram of total protein, and Fig. 6 (C) is rAAV-PTH-hChR2 (H134R) -mcherry-WPRE-pA plasmid sequence map;

Fig. 7 is the experimental process figure of embodiment 5 of the present invention, wherein Fig. 7 (A) is a rat anatomical diagram, Fig. 7 (B) is a schematic diagram of light stimulation in vivo, and Fig. 7 (C) is a rat parathyroid gland injection virus Schematic diagram of post-viral expression;

Fig. 8 is the result diagram of Example 5 of the present invention, wherein Fig. 8(A) is a PTH concentration diagram, Fig. 8(B) is a calcium ion concentration diagram, and Fig. 8(C) is a phosphorus ion concentration diagram.

Detailed ways

In order to further illustrate the technical means and effects adopted by the present invention, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and through specific implementation methods, but the present invention is not limited within the scope of the embodiments.

Example 1

Construction and packaging of CMV promoter lentivirus and PTH promoter adeno-associated virus carrying light-sensitive genes: three plasmids were used to package lentivirus (target gene, PΔ and VSVG) and adeno-associated virus (target gene, pAAV-RC and pHelper ); taking lentiviral packaging as an example, the general process is as follows: mix PΔ (15 μg), VSVG (7 μg) and target gene plasmid (22 μg) carrying light-sensing gene, green fluorescent gene and corresponding promoter, and use liposome FnGENE (Invitrogen) were transfected into 293FT cells together for packaging, and after 24 hours, the virus production medium (DMEM containing 5mM sodium pyruvate) was used to continue culturing, and after 24 hours, the medium supernatant was collected and centrifuged at 1000rpm for five minutes, and the supernatant was taken; 0.45 After filtering the cell residue with a μm filter membrane, transfer the filtrate into a centrifuge tube, and spread a 20% sucrose filter column on the bottom, use a low-temperature ultra-high-speed centrifuge to deposit virus particles at 4 degrees, 20,000 rpm for 2 hours, and pour off the supernatant Then resuspend the virus particles at the bottom of the centrifuge tube with sterile PBS at a volume ratio of 1:1000, and the obtained virus titer can reach more than 3×10 ⁸ TM/mL.

Example 2

The primary human parathyroid principal cell culture system was established and identified by immunostaining, the results are shown in Figure 1(A)-Figure 1(D);

It can be seen from Figure 1(A)-Figure 1(D) that the culture system of human parathyroid chief cells was successfully established and stained successfully;

The obtained lentivirus virus solution was mixed into serum-free and double-antibody-free DMEM at a volume ratio of 1:200 to infect human parathyroid chief cells; after 12 hours, the virus-containing culture medium was replaced with fresh 10% fetal Bovine serum and DMEM with 1% double antibody were cultured for 48 hours and observed under a fluorescent microscope. The results are shown in Figure 2(A) and Figure 2(B);

It can be seen from Figure 2(A) and Figure 2(B) that the green fluorescent marker protein was observed, suggesting that the light-sensing gene marked parathyroid principal cells successfully.

Example 3

Stimulate the cells with blue light of 470nm, 20Hz and 10mW/ ^mm2 for 30 minutes, collect the conditioned medium at 1h, 2h, 4h, 6h and 24h after stimulation, respectively, and detect the changes of PTH secretion by ELISA. The experimental process is shown in Figure 3(A)-figure 3(C), the experimental results are shown in Figure 4(A)-Figure 4(C);

It can be seen from Figure 4(A)-Figure 4(C) that the PTH concentration in the culture medium of the optogenome group was significantly lower than that of the empty shell virus control group expressing only fluorescent protein 1 hour after light stimulation, and then returned to normal levels at 6 hours.

Example 4

The constructed adeno-associated virus with PTH promoter was used to infect the rat parathyroid tissue, and the optogene was expressed in the principal cells. The parathyroid glands of rats were injected (0.4 microliters per side) with the virus vector carrying the light-sensitive gene, and the expression of the virus was monitored by observing the fluorescence expression 21 days after the injection; the isolated parathyroid glands were stimulated with blue light, The medium was collected at various time points to detect the PTH concentration. The experimental process is shown in Figure 5, the results are shown in Figure 6(A) and Figure 6(B), and the plasmid map of the adeno-associated virus is shown in Figure 6(C);

It can be seen from Figure 6(A) and Figure 6(B) that the ELISA test results show that light stimulation can effectively inhibit the release of PTH in a short period of time, and it returns to normal after 6 hours.

Example 5

At the level of animals in vivo, three weeks after the PTH promoter AAV virus was injected into the parathyroid glands of rats, the parathyroid glands were stimulated with blue light, and the average intensity of light was 10mW/mm2. After 15 minutes of stimulation, serum was analyzed by ELISA for changes in PTH concentration, blood calcium and blood phosphorus concentration. The experimental process is shown in Figure 7, and the results are shown in Figure 8(A)-Figure 8(C);

It can be seen from Figure 8(A)-Figure 8(C) that in vivo stimulation of rat parathyroid glands can effectively inhibit the short-term secretion of PTH and have a regulatory effect on calcium and phosphorus.

To sum up, the vector provided by the present invention and the recombinant adeno-associated virus prepared by it can form a system for regulating parathyroid glands with blue-blood, and achieve the function of high-spatial and high-precision specific regulation of parathyroid hormone secretion, which has a wide range of applications prospects and market value.

The applicant declares that the present invention illustrates the detailed methods of the present invention through the above-mentioned examples, but the present invention is not limited to the above-mentioned detailed methods, that is, it does not mean that the present invention must rely on the above-mentioned detailed methods to be implemented. Those skilled in the art should understand that any improvement of the present invention, the equivalent replacement of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the scope of protection and disclosure of the present invention.

sequence listing

<110> Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

<120> A carrier for regulating the secretion of parathyroid gland PTH and its application

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gaagacgaag ccgaggccgg agccgtgcca gcggccgcc 939

Claims (10)

1. A carrier that regulates the secretion of parathyroid PTH, is characterized in that, the carrier includes a photosensitive gene and/or a PTH promoter that specifically recognizes parathyroid principal cells; The nucleic acid sequence of the PTH promoter is shown in SEQ ID NO:1. 2. The carrier according to claim 1, wherein the photosensitive gene is ChR2; Preferably, the nucleic acid sequence of ChR2 is shown in SEQ ID NO:2. 3. A recombinant adeno-associated virus, characterized in that the recombinant adeno-associated virus obtained by co-transfecting the mammalian cells with the carrier according to claim 1 or 2, liposomes and packaging helper plasmids; Preferably, the liposome comprises calcium phosphate, Lipofectamine 2000 or FnGENE, preferably FnGENE; Preferably, the mammalian cells are 293FT cells; Preferably, the packaging helper plasmid includes pAAV-RC and/or pHelper. . 4. A carrier as claimed in claim 1 or 2 is used for preparing a medicine for regulating parathyroid glands. 5. A medicament, characterized in that the medicament comprises the recombinant adeno-associated virus according to claim 3. 6. A system for regulating parathyroid glands, comprising the medicine and blue light as claimed in claim 5; Preferably, the blue light has a wavelength of 450-500nm, preferably 460-480nm; Preferably, the frequency of the blue light is 15-25Hz, preferably 18-22Hz; Preferably, the average intensity of the blue light is 8-12mW/mm ² , preferably 9-11mW/mm ² . 7. A method for regulating parathyroid glands for non-therapeutic purposes, comprising the steps of: (1) construct a lentivirus carrying a CMV promoter, a photosensitive gene and a fluorescent gene; (2) Infecting human parathyroid principal cells with the lentivirus described in step (1), and performing a verification experiment; (3) Using blue light to stimulate the infected cells in step (2), collecting the culture medium to detect changes in PTH; Optionally, the method further comprises constructing the adeno-associated virus according to claim 3 and infecting rat parathyroid tissue, stimulating the tissue with blue light and collecting the culture medium to detect the PTH concentration; (4) Constructing the recombinant adeno-associated virus described in claim 3 and infecting the parathyroid glands of rats, stimulating the parathyroid glands with blue light, collecting serum, and detecting changes in PTH concentration, blood calcium and blood phosphorus concentration. 8. The method according to claim 7, characterized in that the stimulation time in step (3) is 20-40 min, preferably 25-35 min. 9. The method according to claim 7 or 8, characterized in that, the infection method of step (4) is to inject the virus into rat parathyroid glands, and inject 0.2-0.5 microliters on each side; Preferably, the time point of stimulation in step (4) is 18-22 days after infection; Preferably, the detection method is ELISA. 10. A method for regulating parathyroid glands, characterized in that, specifically comprising the steps of: (1) construct a lentivirus carrying a CMV promoter, a photosensitive gene and a fluorescent gene; (2) Infecting human parathyroid principal cells with the virus described in step (1), and performing verification experiments; (3) Using blue light to stimulate the infected cells in step (2), collecting the culture medium to detect changes in PTH; (4) Construct the adeno-associated virus described in claim 3 and inject the parathyroid glands of rats, inject 0.2-0.5 microliters on each side, use blue light to stimulate the isolated parathyroid gland tissue of 18-22 days after infection, and collect the culture medium for detection PTH concentration; (5) Inject the adeno-associated virus described in step (4) into the parathyroid glands of rats, inject 0.2-0.5 microliters on each side, stimulate the parathyroid glands with blue light 18-22 days after infection, collect serum, detect PTH concentration, blood Changes in calcium and phosphorus levels; Wherein, the wavelength of the blue light in step (3), step (4) and step (5) is 450-500nm, the frequency is 15-25Hz, the average intensity of light is 8-12mW/mm ² , and the time is 20-40min.