CN113230340A - Application of kidney-tonifying asthma-preventing prescription in preparation of medicine for treating pulmonary fibrosis - Google Patents
Application of kidney-tonifying asthma-preventing prescription in preparation of medicine for treating pulmonary fibrosis Download PDFInfo
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- A61K36/894—Dioscoreaceae (Yam family)
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Abstract
The invention belongs to the technical field of biomedicine, and particularly relates to application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis. The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis. The application provided by the invention can effectively improve the lung function of pulmonary fibrosis; reduce lung tissue fibrosis; reducing the collagen content of pulmonary fibrosis lung tissues; reduce the expression of lung collagen genes (COL1A1, COL1A2 and COL3A1) and profibrosis genes (PAI-1, CTGF and alpha-SMA) of a mouse pulmonary fibrosis model.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis.
Background
Pulmonary Fibrosis (PF), i.e., pulmonary inflammation and the like, causes persistent damage to alveoli and repeated destruction, repair, reconstruction and excessive deposition of extracellular matrix (ECM), resulting in a fibrotic disease with massive fibroplasia. Pulmonary fibrosis is common pathological change and final outcome of various diffuse interstitial lung diseases, the main clinical manifestations are progressive dyspnea, the final development is hypoxemia and respiratory failure, the average survival time after diagnosis is 3-5 years, and the 5-year survival rate is only 30% -50%.
The treatment of pulmonary fibrosis is still an international problem, which is classified as one of the refractory diseases of the lung system by WHO. At present, main anti-fibrosis drugs comprise immunosuppressants, glucocorticoids, cytokines and antagonists thereof, but the curative effect is mostly unsatisfactory, the adverse reaction is more, and the tolerance is easily caused. Only two drugs for the treatment of pulmonary fibrosis have been approved by the FDA to date. As in 15.10.2014, the FDA approved nintedanib and pirfenidone for the treatment of Idiopathic Pulmonary Fibrosis (IPF). The target points of the two small molecular drugs are Receptor Tyrosine Kinase (RTK) and transforming growth factor TGF-beta respectively, and the two small molecular drugs are single target point drugs. In addition, nintedanib has strong toxic and side effects on the liver, and pirfenidone has strong toxic and side effects on the liver and the kidney. Therefore, there is a need for a safe and effective drug for treating PF.
Disclosure of Invention
In order to solve the problems, the invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis. The kidney-tonifying anti-asthma tablet (Chinese medicine standard Z50020405) related to the application provided by the invention is developed by Shenyinyu hospital of Huashan hospital affiliated to the university of Fudan, has slight toxic and side effects, and can effectively play a role in treating pulmonary fibrosis.
In order to achieve the purpose, the invention provides the following technical scheme:
the invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparing a medicament for improving pulmonary fibrosis and lung functions; the application of the kidney-tonifying asthma-preventing prescription in preparing the medicine for reducing the airway resistance of pulmonary fibrosis is provided.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for relieving pulmonary fibrosis and pulmonary fibrosis.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for reducing the content of lung tissue collagen of pulmonary fibrosis.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for reducing lung tissue collagen genes of pulmonary fibrosis; the collagen genes include COL1a1, COL1a2, and COL3a 1.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparing a medicament for reducing the expression of lung tissue fibrosis-promoting genes of pulmonary fibrosis; the fibrosis promoting genes include PAI-1, CTGF and alpha-SMA.
Preferably, the kidney-tonifying and asthma-preventing prescription consists of radix aconiti lateralis preparata, fructus psoraleae, semen cuscutae, herba epimedii, prepared rehmannia root, radix rehmanniae recen, Chinese yam and dried orange peel; the traditional Chinese medicine composition comprises, by mass, 6 parts of prepared aconite, 10 parts of fructus psoraleae, 10 parts of semen cuscutae, 10 parts of herba epimedii, 10 parts of prepared rehmannia root, 10 parts of radix rehmanniae recen, 10 parts of Chinese yam and 3 parts of dried orange peel.
Preferably, the dosage form of the medicine comprises decoction, tablets, capsules, granules, pills, suspending agents, dispersing agents, syrups or injections.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis. Experiments prove that the application of the traditional Chinese medicine composition can effectively improve the lung function of pulmonary fibrosis; reduce lung tissue fibrosis; reducing the collagen content of pulmonary fibrosis lung tissues; reduce the expression of lung collagen genes (COL1A1, COL1A2 and COL3A1) and profibrosis genes (PAI-1, CTGF and alpha-SMA) of a mouse pulmonary fibrosis model.
Drawings
FIG. 1 shows the results of airway resistance measurements in different groups of mice in example 1;
FIG. 2 is a graph of the pathological changes of lung tissues of mice in different treatment groups tested by HE in example 2;
FIG. 3 shows the pathological changes of lung tissues of mice of different treatment groups detected by Masson staining in example 2;
FIG. 4 is a graph showing the change in expression of mouse lung collagen genes (COL1A1, COL1A2 and COL3A1) detected by Real-time PCR in example 3;
FIG. 5 shows the change in expression of mouse lung tissue profibrosis genes (PAI-1, CTGF, and. alpha. -SMA) detected by Real-time PCR in example 3;
FIG. 6 shows the measurement of collagen content in lung tissue of each group of mice by Sircol assay in example 4.
Detailed Description
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for treating pulmonary fibrosis. The kidney-tonifying and asthma-preventing prescription is preferably composed of radix Aconiti lateralis Preparata, fructus Psoraleae, semen Cuscutae, herba Epimedii, radix rehmanniae Preparata, radix rehmanniae, rhizoma Dioscoreae and pericarpium Citri Tangerinae; the common monkshood daughter root is preferably 6 parts, the malaytea scurfpea is preferably 10 parts, the dodder is preferably 10 parts, the epimedium is preferably 10 parts, the prepared rehmannia root is preferably 10 parts, the dried rehmannia root is preferably 10 parts, the Chinese yam is preferably 10 parts, and the dried orange peel is preferably 3 parts by mass. The kidney-tonifying and asthma-preventing prescriptions mentioned in the following schemes are all consistent with the above, and are not described herein again. The application provided by the invention can play a role in treating pulmonary fibrosis, such as improving lung function of pulmonary fibrosis, relieving pulmonary fibrosis, reducing collagen content of pulmonary fibrosis lung tissue, reducing the expression of mouse pulmonary fibrosis model lung collagen genes (COL1A1, COL1A2 and COL3A1) and fibrosis promotion genes (PAI-1, CTGF and alpha-SMA) and the like.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparing a medicament for improving pulmonary fibrosis and lung functions; the application of the kidney-tonifying asthma-preventing prescription in preparing the medicine for reducing the airway resistance of pulmonary fibrosis is provided. The application provided by the invention can play a role in reducing airway resistance, thereby playing a role in improving pulmonary fibrosis lung function.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for reducing the content of lung tissue collagen of pulmonary fibrosis. The application provided by the invention can effectively reduce the collagen content of a model mouse.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparation of a medicament for reducing the expression of lung collagen genes of pulmonary fibrosis; the collagen genes include COL1a1, COL1a2, and COL3a 1.
The invention provides application of a kidney-tonifying asthma-preventing prescription in preparing a medicament for reducing the expression of lung tissue fibrosis-promoting genes of pulmonary fibrosis; the fibrosis promoting genes include PAI-1, CTGF and alpha-SMA. In the experiment, the expressions of collagen genes and fibrosis promoting genes in the lung tissues of the model mice are obviously increased, and the expressions of the genes can be effectively reduced after the kidney-tonifying asthma-preventing prescription is taken.
In the practical application of the invention, the preparation method of the kidney-tonifying asthma-preventing prescription is preferably decocting into decoction.
In the present invention, the dosage form of the drug preferably includes decoction, tablets, capsules, granules, pills, suspensions, dispersions, syrups or injections. In the present invention, the drugs in different dosage forms preferably further comprise pharmaceutically acceptable excipients.
For further illustration of the present invention, the following detailed description of the application of the kidney-tonifying anti-asthmatic preparation provided by the present invention in preparing the medicine for treating pulmonary fibrosis is provided in the accompanying drawings and examples, but they should not be construed as limiting the scope of the present invention.
Example 1
1. Establishment of pulmonary fibrosis mouse model:
a Bleomycin (BLM) induced pulmonary fibrosis model was established by endotracheal intubation using 7-week-old C57BL/6 female mice. The dosage of the bleomycin is 9mg/kg, and the bleomycin is administered at one time.
2. The preparation method of the compound water decoction for tonifying the kidney and preventing asthma comprises the following steps:
the mass ratio of the prepared aconite, the psoralea fruit, the dodder seed, the epimedium herb, the prepared rehmannia root, the dried rehmannia root, the yam and the dried orange peel is 6: 10: 10: 10: 10: 10: 10: 3.
the preparation method comprises the following steps: decocting radix Aconiti lateralis Preparata in water for 2 hr, and filtering with sterile gauze to obtain radix Aconiti lateralis Preparata filtrate and residue; decocting the residue and other decoction pieces in water for 3 times, respectively decocting for 2 hr for 1 st and 2 nd times, decocting for 1 hr for 3 rd time, filtering, mixing the three filtrates, adding radix Aconiti lateralis Preparata filtrate to obtain mixture, and concentrating the mixture to 1g/mL to obtain medicine for invigorating kidney and relieving asthma (BSFC).
3. Group and kidney tonifying antiasthmatic prescription (BSFC):
mice were divided into 5 groups: the unmodeled 7-week-old C57BL/6 female mice were set as a Control group (Control), a BLM model group mouse (BLM), and a low/medium/high different dose drug group mouse (BSFC-L, BSFC-M and BSFC-H) based on the disease model group mouse.
The specific administration operation is as follows:
1、BLM：
after 1 week of tracheal instillation of bleomycin, the stomach was perfused with the same volume of physiological saline as BSFC for 1 time per day for 3 weeks.
2. BSFC-H, BSFC-M and BSFC-L: after 1 week of tracheal instillation of bleomycin, different doses of the kidney-tonifying and asthma-preventing prescription are administered by a gavage needle 1 time a day, the medicament is continuously administered for 3 weeks, the dosage of BSFC-L is 5 g/kg/day, the dosage of BSFC-M is 10 g/kg/day, and the dosage of BSFC-H is 20 g/kg/day;
3. control: mice in the control group were gavaged with BSFC in the same volume of saline 1 time a day for 3 weeks.
4. Pulmonary function detection
The mice were anesthetized with 2% pentobarbital sodium solution 24 hours after the end of the last dose. The neck skin was then cut open and the subcutaneous soft tissue was bluntly separated, exposing the trachea. A small opening is cut at the center of the trachea by an ophthalmic scissors, and the intubation is carried out by using an intubation needle matched with an instrument and is immediately tested on a machine. The lung function of the mice was measured by Buxco PFT (pulmonary function testing) system, and the results are shown in FIG. 1.
As shown in FIG. 1, when different groups of Control, BLM, BSFC-H, BSFC-M and BSFC-L were challenged with 3.125, 6.25mg/ml of methacholine (Mch), respectively, the airway resistance of the BLM group mice was significantly increased (P <0.05) compared to the Control group; the airway resistance of mice in both the BSFC-L, BSFC-M and BSFC-H groups was significantly reduced (P <0.05) compared to the BLM group and was dose-dependent, with the BSFC-H group airway resistance approaching that of the Control group. The application provided by the invention can effectively reduce the airway resistance of the pulmonary fibrosis model mouse.
Example 2
The fibrotic lung tissues of the mice described in example 1 were obtained, one part was frozen, the other part was fixed with formalin for one week and used for paraffin section preparation, HE staining and Masson staining were performed on the sections, inflammation of lung tissues and pulmonary fibrosis were observed under light microscope, and the degree of pulmonary fibrosis of each group of mice was compared. The HE staining results are shown in fig. 2, and the Masson trichrome staining results are shown in fig. 3.
As can be seen from FIG. 2, the HE staining result shows that pulmonary tissues of mice perfused with BLM through trachea have thickened alveolar spaces, local lung is damaged and infiltrated with a large amount of inflammatory cells, and obvious inflammatory reaction is generated;
as can be seen from FIG. 3, Masson's trichrome staining results showed that lung tissues of mice perfused with BLM through trachea had a large amount of collagen fiber deposition, and pulmonary fibrosis was severe.
The comparison between the BSFC-L, BSFC-M group and the BSFC-H group and the Control group and the BLM group shows that the application provided by the invention can obviously relieve the lung tissue pathological changes induced by bleomycin, has dose dependence, and has better effects of inhibiting lung inflammation and fibrosis by a high-dose kidney-tonifying asthma-preventing prescription than a low-dose group.
Example 3
The mouse tissue of example 1 was cryopreserved, and the cryopreserved tissue was examined for expression of fibrosis-associated genes by Real-time PCR. The Real-time PCR results are shown in FIGS. 4 and 5; in FIGS. 4 and 5, the ordinate axis Fold change descriptor is the Fold difference of gene mRNA expression.
As can be seen from FIGS. 4 and 5, the Real-time PCR results showed that the expression of collagen genes (COL1A1, COL1A2, and COL3A1) was significantly increased in lung tissues of the mice in the BLM group as compared with the Control group; the BSFC-L, BSFC-M and BSFC-H groups reduced the expression of the collagen gene (P <0.05) compared to the BLM group, especially at high doses.
The trends of the genes promoting fibrosis (PAI-1, CTGF and alpha-SMA) are consistent with those of the collagen gene (P < 0.05).
Example 4
The expression of collagen was detected by the Sircol assay, and the detection results are shown in FIG. 6, where Fold change of collagen content is the Fold difference of the ordinate axis.
As shown in fig. 6, the quantitative detection of Sircol assay showed that the collagen content of BLM mice was about 2.39 times that of Control mice, while the collagen content was significantly reduced after different doses of kidney-tonifying anti-asthmatic drugs were administered, which is also dose-dependent.
In conclusion, the kidney-tonifying asthma-preventing medicine can play a role in treating pulmonary fibrosis from various aspects.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (8)
1. Application of the kidney-tonifying asthma-preventing medicine in preparation of a medicine for treating pulmonary fibrosis.
2. Application of the kidney-tonifying asthma-preventing prescription in preparing a medicament for improving pulmonary fibrosis lung function; the application of the kidney-tonifying asthma-preventing prescription in preparing the medicine for reducing the airway resistance of pulmonary fibrosis is provided.
3. Application of the kidney-tonifying asthma-preventing medicine in preparation of a medicine for relieving pulmonary fibrosis and pulmonary fibrosis tissue fibrosis.
4. Application of the kidney-tonifying asthma-preventing preparation in preparation of a medicine for reducing the content of lung tissue collagen of pulmonary fibrosis.
5. The application of the kidney-tonifying asthma-preventing medicine in preparing the medicine for reducing the lung tissue collagen gene of the pulmonary fibrosis; the collagen genes include COL1a1, COL1a2, and COL3a 1.
6. The application of the kidney-tonifying asthma-preventing medicine in preparing the medicine for reducing the expression of lung tissue fibrosis-promoting genes of pulmonary fibrosis; the fibrosis promoting genes include PAI-1, CTGF and alpha-SMA.
7. The use according to any one of claims 1 to 6, wherein the kidney-tonifying and asthma-preventing prescription is composed of radix Aconiti lateralis Preparata, fructus Psoraleae, semen Cuscutae, herba Epimedii, radix rehmanniae Preparata, radix rehmanniae, rhizoma Dioscoreae and pericarpium Citri Tangerinae; the traditional Chinese medicine composition comprises, by mass, 6 parts of prepared aconite, 10 parts of fructus psoraleae, 10 parts of semen cuscutae, 10 parts of herba epimedii, 10 parts of prepared rehmannia root, 10 parts of radix rehmanniae recen, 10 parts of Chinese yam and 3 parts of dried orange peel.
8. The use of any one of claims 1 to 6, wherein the medicament is in the form of decoction, tablet, capsule, granule, pill, suspension, dispersion, syrup or injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102293896A (en) * | 2011-08-26 | 2011-12-28 | 太极集团重庆涪陵制药厂有限公司 | Preparation method of tablet for tonifying kidney and asthma |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102293896A (en) * | 2011-08-26 | 2011-12-28 | 太极集团重庆涪陵制药厂有限公司 | Preparation method of tablet for tonifying kidney and asthma |
Non-Patent Citations (1)
| Title |
|---|
| 瞿岳云主编: "《中医补益全书【珍藏本】超值版》", 31 August 2013 * |
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