CN111067913B - Application of dioscin in preparation of pulmonary artery hypertension protection medicine - Google Patents
Application of dioscin in preparation of pulmonary artery hypertension protection medicine Download PDFInfo
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- A61P9/12—Antihypertensives
Abstract
The invention discloses application of dioscin in preparation of a pulmonary hypertension protection drug. Dioscin can effectively inhibit proliferation of the PASMCs in vitro and weaken migration capacity of cells, and TUNEL results show that the apoptosis number of the PASMCs given to the dioscin is obviously increased. The results show that the dioscin can obviously reduce the pulmonary arterial blood vessel pressure and the right ventricular systolic pressure of a rat pulmonary artery high pressure model induced by chronic hypoxia or MCT (methyl thiazolyl tetrazolium) and reduce the right ventricular index and improve the condition of the right ventricular hypertrophy.
Description
Technical Field
The invention relates to a new application of effective components of traditional Chinese medicines, in particular to an application of high-purity dioscin in preparing a pulmonary hypertension protection medicine.
Background
At present, a plurality of reports of Chinese herbal compound medicines such as Tongxinluo and Sanhuang Xiexin decoction, Chinese herbal extract cordyceps sinensis extract and monomer compounds such as tetrandrine, hydroxyl carthamin yellow A and the like can obviously improve pulmonary hypertension, and the feasibility of the Chinese herbal medicine on treating pulmonary hypertension vascular remodeling is shown. Therefore, the active and deep research on the action mechanism of the Chinese herbal medicine and the definition of action targets have great significance. Dioscin is widely present in plants of Dioscoreaceae, Caryophyllaceae, Rosaceae, Liliaceae, etc., and is a triterpenoid saponin compound with high content in rhizome of Dioscorea nipponica Makino (Discorea nipponica Makino) of Dioscoreaceae. The dioscin is a key raw material for synthesizing steroid hormone medicaments, and has various pharmacological activities, anti-inflammatory, antioxidant, anti-tumor, anti-infection, blood fat reducing and liver protecting effects. The dioscin can remarkably inhibit the expression of Vascular Endothelial Growth Factor Receptor (VEGFR)2, phosphoinositide 3 kinase (PI3K), phosphorylated AKT and phosphorylated p38 mitogen-activated protein kinase (MAPK) proteins of human ovarian cancer cells, induces the apoptosis of the ovarian cancer cells in a dose-dependent manner by regulating VEGFR 2 and PI3K/AKT/MAPK signal pathways, and inhibits the proliferation and metastasis of the ovarian cancer cells.
Disclosure of Invention
The invention finds that the dioscin has a protective effect on pulmonary hypertension, and provides application of the dioscin in preparation of a pulmonary hypertension protective drug. In particular to the application of dioscin in preparing a pulmonary hypertension protection medicament, in particular to the improvement effect on pulmonary hypertension vascular remodeling.
The invention provides application of dioscin in preparation of a pulmonary hypertension protection medicine, and dioscin can be prepared into a medicinal preparation with a single chemical component or a compound medicinal preparation by being combined with other medicines. Can also be prepared into various dosage forms according to the relevant requirements of pharmacy and clinical needs, and can be applied to clinic, such as: tablet, capsule, injection, oral liquid, granule, etc.
Further, the application of dioscin in inhibiting proliferation and migration of pulmonary artery smooth muscle cells and promoting apoptosis; the application of dioscin in improving the systolic pressure of right ventricle and the rise of the right ventricular hypertrophy index of hypoxia or MCT (methyl cellulose acetate) -induced pulmonary hypertension; the application of dioscin in improving blood vessel wall thickening, cell hypertrophy and hyperproliferation is provided.
The invention discloses application of dioscin in preparation of a pulmonary hypertension protection drug, and particularly relates to an oral administration mode under the condition that oral administration is adopted, wherein oral dioscin (15, 30 and 60mg/kg) for rats has an obvious protection effect on pulmonary hypertension, and the oral dioscin (60kg) for an adult (2.3-9.17 mg/kg body weight) daily has an obvious protection effect on pulmonary hypertension by calculation clinically.
The invention discovers that the dioscin has the function of protecting the pulmonary hypertension and can be used for preparing a pulmonary hypertension protection medicament. MTT and cell morphology research results show that the hypoxia state of the model group remarkably promotes the proliferation of the PASMCs (rat pulmonary artery smooth muscle cells) compared with the Nor + 5% FBS of the control group, and the number of the PASMCs is reduced and the proliferation is obviously limited compared with the model group in the dioscin administration group.
Cell migration results show that compared with a control group, the model group has obvious migration of the PASMCs after 48 hours of hypoxia, and the cell migration distance is obviously shortened after the dioscin (0.3, 0.6 and 1.2 mu M) is given in advance, which shows that the dioscin can inhibit the migration of the PASMCs in vitro.
For the hypoxia-induced pulmonary artery hypertension vascular remodeling of rats, compared with a hypoxia model group, after dioscin treatment (15, 30 and 60mg/kg), pulmonary artery pressure is obviously reduced and tends to be 25mmHg, meanwhile, Right Ventricular Systolic Pressure (RVSP) is gradually reduced compared with the model group, the pressure value is close to that of a control group, and the right ventricular hypertrophy index (RV/LV + S) of the treatment group is also obviously reduced compared with the model group, which indicates that the dioscin can effectively improve the hypoxia-induced pulmonary artery hypertension vascular remodeling of rats.
In MCT (monocrotaline) -induced pulmonary arterial hypertension vascular remodeling of rats, pulmonary arterial pressure, RVSP and RV/LV + S in an MCT model group are abnormally increased, dioscin can effectively inhibit the phenomenon from generating at concentrations of 15, 30 and 60mg/kg, the pulmonary arterial pressure, the RVSP and the RV/LV + S are obviously reduced and are close to normal values, and the effect of the dioscin on resisting MCT-induced pulmonary arterial hypertension vascular remodeling of rats is obvious.
Drawings
FIG. 1 is a graph showing the inhibition of proliferation of PASMCs by dioscin according to example 1 of the present invention; compared with the control group, the compound of the formula,##p<0.01; in comparison to the set of models,**p<0.01(n＝6)。
FIG. 2 is a graph showing the effect of dioscin on the morphology of PASMCs in example 1 of the present invention.
FIG. 3 is a graph showing the inhibitory effect of dioscin on the migration of PASMCs in example 1 of the present invention.
FIG. 4 is the TUNEL assay of dioscin for apoptosis of PASMCs in vitro according to example 1 of the present invention.
FIG. 5 shows the effect of dioscin on hypoxia-induced pulmonary hypertension vascular remodeling hemodynamics and cardiac function of rats in example 2 of the present invention; a, the pressure of the pulmonary artery blood vessel of the rat; rat Right Ventricular Systolic Pressure (RVSP); right ventricular hypertrophy index (RV/LV + S); compared with the control group, the compound of the formula,##p<0.01; in comparison to the set of models,*p<0.05,**p<0.01(n＝10)。
FIG. 6 is a graph of H & E measurements of Hyp-induced pulmonary hypertension pulmonary vascular tissue with dioscin in example 2 of the present invention.
FIG. 7 shows the tissue TUNEL detection result of the Hyp-induced pulmonary arterial hypertension revascularization by dioscin in example 2 of the present invention.
FIG. 8 is a graph of the effects of dioscin on MCT-induced PAH vascular remodeling hemodynamics and cardiac function in example 3 of the present invention; a, the pressure of the pulmonary artery blood vessel of the rat; rat Right Ventricular Systolic Pressure (RVSP); right ventricular hypertrophy index (RV/LV + S); compared with the control group, the compound of the formula,##p<0.01; in comparison to the set of models,*p<0.05,**p<0.01(n＝10)。
FIG. 9 is the H & E assay of MCT-induced pulmonary hypertension pulmonary vascular tissue with dioscin in according to example 3 of the present invention.
FIG. 10 shows the tissue TUNEL detection result of the dioscin in MCT-induced pulmonary hypertension revascularization in example 3 of the present invention.
Detailed Description
The following non-limiting examples will allow one of ordinary skill in the art to more fully understand the present invention, but are not intended to limit the invention in any way.
Example 1 study of protective effects of dioscin on in vitro PASMCs
1. MTT assay cell viability
Extracting and identifying rat primary PASMCs (rat pulmonary artery smooth muscle cells), taking 3-5 generations of PASMCs (rat pulmonary artery smooth muscle cells) in logarithmic growth phase with good state, digesting with pancreatin, centrifuging to prepare single cell suspension, and taking the cell concentration of the PASMCs as 1 multiplied by 105one/mL was seeded into 96-well plates with 100. mu.L of cell suspension per well. The experiment was performed when the growth was to about 70% of the area of the bottom of the well under normal incubation conditions. The grouping situation is as follows: normoxic (Normoxic, Nor) + 20% FBS, Normoxic (Normoxic, Nor) + 5% FBS, hypoxic (Hypoxia, Hyp, 10% O)2) + 5% FBS, hypoxic group, 10% O2+ 5% FBS + dioscin 0.3. mu.M (Hyp + 5% FBS + Dio 0.3), hypoxic group, 10% O2+ 5% FBS + Dio 0.6. mu.M (Hyp + 5% FBS + Dio 0.6), hypoxic group, 10% O2+ 5% FBS + Dio 1.2. mu.M (Hyp + 5% FBS + Dio 1.2). Adding culture medium containing fetal calf serum or dioscin solution with different concentrations into each well according to different groups, replacing anoxic groups to a three-gas incubator after 24h, and setting O2、N2、CO2The concentration is 1%, 94% and 5%, the normoxic group is still incubated under normal culture condition, MTT is added after 48h, and the absorbance value of each well is detected, thus calculating the cell viability.
In the study for investigating the effect of dioscin on inhibiting cell proliferation of the PASMCs, as can be seen from fig. 1, the hypoxia state of the model group (Hyp + 5% FBS) significantly promotes the proliferation of the PASMCs cells compared with the Nor + 5% FBS of the control group, while the cell number of the PASMCs cells of the dioscin administration group (Hyp + 5% FBS + Dio0.3, Hyp + 5% FBS + Dio 0.6, Hyp + 5% FBS + Dio1.2) is reduced and the proliferation is significantly limited compared with the model group. The influence of dioscin on the PASMCs is discussed by observing the cell morphology, and as can be seen from figure 2, compared with a control group (Nor + 5% FBS), the cell number in a model group established by 48h hypoxia is obviously increased, and after dioscin (0.3, 0.6 and 1.2 mu M) is given to act for 24h in advance, the cell number is obviously reduced and the apoptosis is increased compared with a hypoxia model group.
2. Scratch test for detecting cell migration
Collecting 3-5 generations of PASMCs with good growth state, performing pancreatin digestion, centrifuging, and making into single cell suspension with cell concentration of PASMCs of 1 × 105one/mL was inoculated into six well plates, 2mL per well. After culturing under normal conditions until the cells were confluent on the bottom surface, serum was deprived, starved for 24h, scratched with a 200 μ L tip, washed once with PBS, photographed under microscope observation, and then culture medium containing FBS at various concentrations and a dioscin solution (0.3, 0.6, 1.2 μ M) were administered in groups of concentrations, respectively. And placing the normoxic group in a normal incubator, placing the hypoxic group in a three-gas incubator, after culturing for 48h, placing the same part under a microscope for photographing again, comparing with the scratch of 0h, and detecting the migration capacity of the cells.
In the study, the influence of dioscin on the PASMCs is discussed by observing the cell morphology, as can be seen from fig. 3, compared with a control group, the number of cells in a model group established by hypoxia 48 is obviously increased, and after dioscin (0.3, 0.6 and 1.2 mu M) is given to act for 24 hours in advance, the number of cells is obviously reduced and the apoptosis is increased compared with that of an anoxic model group.
4. TUNEL method for detecting apoptosis
Collecting 3-5 generations of PASMCs with good growth state, performing pancreatin digestion, centrifuging, and making into single cell suspension with cell concentration of PASMCs of 1 × 105one/mL was inoculated into 24-well plates and 500. mu.L of cell suspension was added to each well. The experiment can be carried out under normal incubation conditions overnight when the cells grow to 70-80% of the basal area. The grouping situation is as follows: normoxia group (Nor) + 20% FBS, normoxia group (Nor) + 5% FBS, hypoxia group (Hyp, 10% O)2) + 5% FBS, hypoxic group (Hyp, 10% O)2) + 5% FBS + Dio0.3, hypoxic group (Hyp, 10% O)2) + 5% FBS + Dio 0.6, hypoxic group (Hyp, 10% O)2) + 5% FBS + Dio 1.2; respectively administering culture medium containing FBS with different concentrations and dioscin solution (0.3, 0.6, 1.2 μ M) according to group concentration, replacing anoxic group with three-gas incubator after 24 hr, and setting O2、N2、CO2The concentration is 1%, 94% and 5%, the normoxic group is still incubated under normal culture condition, and the cells are taken out after incubation for 48 h. Fixing 500 μ L of 4% paraformaldehyde in each well at room temperature for 0.5 hr, washing with 1 × PBS 3 times, standing for 5min, sucking off residual liquid, and dripping 0.3% Triton-X100 into each wellPassing 100 μ L of the Solution through the wells, passing through the wells at room temperature for 5min, adding 100 μ L of a mixture (V/V,50:2) of 1 × Labeling Solution and TdT (terminal transferase) into each well, keeping out of the light, Labeling at 37 ℃ for 1.5h, adding 100 μ L of the Solution through each well after Labeling, standing at room temperature for 5min, completely sucking, repeating the process for 3 times, adding 200 μ L of 1 × PBS into each well, placing the cells under a fluorescence microscope, observing fluorescence at 200 times, and taking pictures.
The effect of dioscin on the apoptosis of the PASMCs is detected by TUNEL staining, the experimental result is shown in figure 4, the fluorescence of the model group (Hyp + 5% FBS) is weaker compared with that of the control group (Nor + 5% FBS), the number of cells in an apoptotic state is less, and the green fluorescence proportion is obviously increased and the apoptosis is increased after the dioscin is treated at the concentrations of 0.3 mu M, 0.6 mu M and 1.2 mu M.
5. Statistical analysis
The experimental result is expressed by mean ± standard deviation (mean ± s.d.), GraphPad 5.0 statistical analytical software is used for data analysis, and t-test is used for sample mean comparison between two groups; the mean-average sample comparison among groups adopts One-Way ANOVA analysis of variance, and when p is less than 0.05, the significant difference is considered to exist.
Example 2 protective Effect of Dioscorea opposita Saponin on vascular remodeling of hypoxic rat PAH
1. Grouping modeling and processing of experimental animals
Healthy male SPF grade SD rats were 50, randomized into five groups: blank control group: normoxia group (Nor), model group: hypoxic group (Hyp, 10% O)2) Administration group of dioscin: hypoxic group (Hyp, 10% O)2) + different doses dioscin were administered intragastrically (15, 30 and 60mg/kg), and the experiment was started one week after adaptation to free water and food intake. Feeding the blank control group in normal oxygen environment for 3 weeks, performing intragastric adaptation 2 days in advance, placing into animal experimental box together with anoxia model group, and anoxia (10% O)2) And (3) molding for 3 weeks, wherein the administration group of dioscin adheres to intragastric administration for 1 time/day during the molding period, and the normoxic group and the hypoxia model group are simultaneously administered with corresponding volumes of physiological saline for intragastric administration for 3 weeks. Performing blood pressure detection by inserting a right external jugular vein for 23 days, taking blood from abdominal aorta, killing, centrifuging the blood at 4 ℃ and 3500rpm for 10min to obtain serum, and storing at-80 ℃; getPart of lung tissue was fixed in 10% formaldehyde solution for pathology; the remaining lung tissue was left at-80 ℃ for use.
2. Hemodynamic monitoring
SD rats are weighed, anesthetized with a corresponding dose of anesthetic, fixed on a rat board, sheared and disinfected at an operation position, an opening right above a sternum along the midline skin is about 1cm long, muscle fascia is removed, external jugular veins are separated in a blunt manner, ligation is carried out at the far end, and a socket is carefully cut. The catheter wetted by heparin is inserted into a vein and slowly pushed, the catheter is inserted into the vein by 1-2cm and can pass through the junction of the axillary vein and the external jugular vein, the right atrium can be accessed by continuously pushing 1-2cm, the catheter is properly pushed in a rotating mode, the sensed resistance is remarkably reduced, and when the waveform of the right ventricle is observed by a physiological instrument, the catheter is indicated to have accessed the right ventricle. Stopping for a moment, making the catheter flow to the pulmonary artery, slowly pushing, constantly paying attention to the physiological instrument, when the waveforms of M and N appear alternately, indicating that the catheter is placed in the pulmonary artery, fixing the catheter by a wire tie, observing and recording the pressure curve of the pulmonary artery.
For hypoxia-induced pulmonary hypertension revascularization in rats, as shown in fig. 5A, after dioscin treatment (15, 30 and 60mg/kg), pulmonary arterial pressure was significantly reduced to a normal value of 25mmHg as compared to the hypoxic model group, while Right Ventricular Systolic Pressure (RVSP) was also gradually reduced compared to the model group (fig. 5B), the pressure value was close to that of the control group, and right ventricular hypertrophy index (RV/LV + S) was also significantly reduced compared to the model group (fig. 5C), indicating that dioscin was effective in improving hypoxia-induced pulmonary hypertension revascularization in rats.
3. Histopathology
After completion of the pulmonary artery pressure test, the rats were sacrificed and the cardiopulmonary tissues were removed. Removing blood vessels and envelopes, separating a Left Ventricle (LV), a Right Ventricle (RV) and a ventricular septum (IVS), washing with normal saline, sucking dry water stains by filter paper, weighing, and calculating RV/LV + S, namely the Right ventricular hypertrophy index. The pulmonary vascular tissue is fixed in 4% paraformaldehyde, and then is fixed on a glass slide, and the pathological changes of the tissue are observed and analyzed by hematoxylin-eosin (H & E) staining.
From the results of fig. 6, it can be seen that in the rat pulmonary artery hypertension vascular remodeling model induced by hypoxia and Hyp, the vascular wall of the model group is abnormally thickened and the lumen is narrowed, and compared with the abnormal tissue structure of the model group, the vascular wall of the dioscin treatment group (15, 30 and 60mg/kg) is obviously thinned, the lumen is widened and gradually restored to present a normal vascular structure, which indicates that the dioscin can obviously reverse the pulmonary artery hypertension vascular remodeling induced by hypoxia or Hyp.
5. Tissue section TUNEL detection
Paraffin sections are dewaxed and rehydrated by dimethylbenzene and gradient ethanol, then soaked in PBS and kept stand for 5 minutes, the sections are taken out and peripheral liquid is carefully sucked, and the sections are ensured to be kept wet. 100. mu.L of cell permeation solution (TritonX-100) was dropped onto the surface of each slice at room temperature, and the mixture was allowed to stand for 5 min. Then uniformly mixing 1 × Labeling Solution and TdT according to a ratio of 50 μ L:2 μ L, dripping and covering the surface of the slice sample, incubating at 37 ℃ in a dark place for 1.5h, dripping 100 μ L of cell permeation Solution on the slice sample after Labeling, incubating at room temperature for 5min, completely sucking the liquid around the slice, carefully repeating the step for 3 times, completely sucking the liquid around the slice, dripping an anti-quenching blocking tablet, and sealing the slice with a cover glass, wherein the process is carried out in a wet box, the problem that the sample is dried in the experimental process to cause the failure of the experiment is avoided, and then observing and photographing at 200 times under a fluorescence microscope.
Fig. 7 shows that the apoptosis of the PASMCs is less in the hypoxia-induced pulmonary hypertension vascular remodeling model, while the apoptosis number of the dioscin administration groups (15, 30 and 60mg/kg) is much higher than that of the model group, and the inhibition of the PASMCs apoptosis induced by hypoxia is remarkably reversed.
Example 3 protective Effect of dioscin on PAH vascular remodeling in MCT rats
1. Grouping modeling and processing of experimental animals
Healthy male SPF grade SD rats were 50, randomized into five groups: blank group (single injection of normal Saline, salene), monocrotaline model group (MCT model group), dioscin administration group: monocrotaline (MCT) + different doses of dioscin were gavaged (15, 30 and 60 mg/kg). The dioscin administration group starts intragastric administration for adaptation 2 days in advance, then performs single intraperitoneal injection of monocrotaline (60mg/kg) together with the model group, performs single intraperitoneal injection of normal saline in the blank group, continuously performs intragastric administration for 3 weeks in the dioscin administration group, performs intragastric administration for the blank group and the MCT model group simultaneously by giving corresponding volumes of normal saline, completes molding after 3 weeks, and performs treatment. Performing blood pressure detection by inserting a right external jugular vein for 23 days, taking blood from abdominal aorta, killing, centrifuging the blood at 4 ℃ and 3500rpm for 10min to obtain serum, and storing at-80 ℃; fixing part of lung tissues in 10% formaldehyde solution for pathological study; the remaining lung tissue was left at-80 ℃ for use.
2. Hemodynamic monitoring
SD rats are weighed, anesthetized with a corresponding dose of anesthetic, fixed on a rat board, sheared and disinfected at an operation position, an opening right above a sternum along the midline skin is about 1cm long, muscle fascia is removed, external jugular veins are separated in a blunt manner, ligation is carried out at the far end, and a socket is carefully cut. The catheter wetted by heparin is inserted into a vein and slowly pushed, the catheter is inserted into the vein by 1-2cm and can pass through the junction of the axillary vein and the external jugular vein, the right atrium can be accessed by continuously pushing 1-2cm, the catheter is properly pushed in a rotating mode, the sensed resistance is remarkably reduced, and when the waveform of the right ventricle is observed by a physiological instrument, the catheter is indicated to have accessed the right ventricle. Stopping for a moment, making the catheter flow to the pulmonary artery, slowly pushing, constantly paying attention to the physiological instrument, when the waveforms of M and N appear alternately, indicating that the catheter is placed in the pulmonary artery, fixing the catheter by a wire tie, observing and recording the pressure curve of the pulmonary artery.
As can be seen from FIG. 8, in the monocrotaline-induced pulmonary arterial hypertension revascularization of rats, the pulmonary arterial pressure, RVSP and RV/LV + S in the monocrotaline model group were all abnormally increased, and dioscin at concentrations of 15, 30 and 60mg/kg could effectively inhibit the generation of this phenomenon, significantly reduce the pulmonary arterial pressure, RVSP and RV/LV + S and make them close to normal values, indicating that dioscin has significant efficacy in resisting MCT-induced PAH revascularization of rats.
3. Histopathology
After completion of the pulmonary artery pressure test, the rats were sacrificed and the cardiopulmonary tissues were removed. Removing blood vessels and envelopes, separating a Left Ventricle (LV), a Right Ventricle (RV) and a ventricular septum (IVS), washing with normal saline, sucking dry water stains by filter paper, weighing, and calculating RV/LV + S, namely the Right ventricular hypertrophy index. The pulmonary vascular tissue is fixed in 4% paraformaldehyde, and then is fixed on a glass slide, and the pathological changes of the tissue are observed and analyzed by hematoxylin-eosin (H & E) staining.
From the results of fig. 9, it can be seen that, in the monocrotaline-induced pulmonary artery hypertension vascular remodeling model of rats, the vascular wall of the model group is abnormally thickened and the lumen is narrowed, and compared with the abnormal tissue structure of the model group, the dioscin treatment groups (15, 30 and 60mg/kg) enable the vascular wall to be obviously thinned, widen the lumen and gradually recover to present a normal vascular structure, which indicates that the dioscin can obviously reverse MCT-induced pulmonary artery hypertension vascular remodeling.
5. Tissue section TUNEL detection
Paraffin sections are dewaxed and rehydrated by dimethylbenzene and gradient ethanol, then soaked in PBS and kept stand for 5 minutes, the sections are taken out and peripheral liquid is carefully sucked, and the sections are ensured to be kept wet. At room temperature, 100. mu.L of cell permeation solution was dropped on the surface of each slice, and the mixture was allowed to stand for 5 min. Then uniformly mixing 1 × Labeling Solution and TdT according to a ratio of 50 μ L:2 μ L, dripping and covering the surface of the slice sample, incubating at 37 ℃ in a dark place for 1.5h, dripping 100 μ L of cell permeation Solution on the slice sample after Labeling, incubating at room temperature for 5min, completely sucking the liquid around the slice, carefully repeating the step for 3 times, completely sucking the liquid around the slice, dripping an anti-quenching blocking tablet, and sealing the slice with a cover glass, wherein the process is carried out in a wet box, the problem that the sample is dried in the experimental process to cause the failure of the experiment is avoided, and then observing and photographing at 200 times under a fluorescence microscope.
FIG. 10 shows that hypoxia or MCT-induced apoptosis of PASMCs in pulmonary arterial hypertension revascularization models is low, while the numbers of apoptosis in the dioscin-administered groups (15, 30 and 60mg/kg) are much higher than those in the model groups, and the inhibition of PASMCS apoptosis induced by MCT is significantly reversed.
Claims (3)
1. The application of dioscin in preparing a pulmonary hypertension protection medicine is characterized in that: the application of dioscin in improving the systolic pressure of right ventricle and the rise of right ventricular hypertrophy index of hypoxia-induced pulmonary hypertension is provided.
2. The use of dioscin according to claim 1 in the preparation of a pulmonary hypertension protection drug, wherein: the dioscin is prepared into a medicinal preparation with a single chemical component, or is combined with other medicaments to prepare a compound medicinal preparation.
3. The use of dioscin according to claim 1 in the preparation of a pulmonary hypertension protection drug, wherein: the application of dioscin in inhibiting proliferation and migration of pulmonary artery smooth muscle cells and promoting apoptosis; the application of dioscin in improving blood vessel wall thickening, cell hypertrophy and hyperproliferation is provided.
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| CN1966031A (en) * | 2005-12-16 | 2007-05-23 | 李民主 | Medicament for preventing and treating ageing diseases |
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| CN1966031A (en) * | 2005-12-16 | 2007-05-23 | 李民主 | Medicament for preventing and treating ageing diseases |
| CN111961669A (en) * | 2014-05-01 | 2020-11-20 | Ionis制药公司 | Compositions and methods for modulating angiopoietin-like protein 3 expression |
| CN106074581A (en) * | 2016-07-01 | 2016-11-09 | 中央民族大学 | Vascular protection pharmaceutical composition and application thereof |
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