| Object ive:By observing the effects of Compound Danshen Dropping Pills on cardiac function and tissue structure,myocardial related protein TGF-beta l,Collagen I,VEGF and miR-200b gene expression in type 2 diabetic rats,the possible mechanism of Compound Danshen Dropping Pills in preventing and treating cardiomyopathy in type 2 diabetic rats was discussed.Method:After one week of adapt.ive feeding,male SD rats were randomly divided into control group and module group.Rats in the control group were fed with common diet,while rats in the module group were fed with combined method(high-sugar and high-fat diet+sucrose water+high-sugar and high-fat milk).After 6 weeks of continuous feeding,the rats in the module group were weighed at the 7th week.If the body mass of the module group)the body mass of mean+2 SD in the control group(the food-induced obese rats)were included,all the other rats that did not meet the standard were removed.The rats in the module group were fed only with high-fat and high-sugar diet and drinking water of common experimental animals,and the sucrose and high-fat and high-sugar milk feeding were interrupted until the end of the experiment.Rat.s in the module group were injected with 1%STZ in a single intraperitoneal injection at a dose of 28 mg/kg,while rats in the control group were injected with the same amount of sodium citrate buffer in a single intraperitoneal injection.After injection of STZ,rats i:n the module group were tested for fasting blood glucose(fasting for 8 hours)by tail tip blood sampling for 12 weeks,four consecutive fasting blood glucose greater than 11.1 mmol/L and with "a little more than three disease"(polydipsia,polyphagia,polyuria,and weight loss)were included in the experiment.The rats in the module group were randomly divided into three groups:model group,Compound Danshen Dropping Pill group and metformin group.Rats in the Compound Danshen Dropping Pills group and metformin group were given 500 mg/kg of the corresponding drug solution per day,while rats in the blank group and model group were given the same volume of distilled water per day for 12 weeks.The cardiac function was evaluated by echocardiography at the end of 12 weeks.After 12 weeks of intervention,the blood samples were collected and the related indicators were detected:glycosylated hemoglobin and fasting insulin were measured by ELISA;fasting blood glucose,triglyceride,total cholesterol,low density lipoprotein cholesterol,high density lipoprotein cholesterol were measured by automatic biochemical instrument;malondialdehyde and superoxide dismutase in rat serum were measured by biochemical kit;the rat heart was preserved,heart mass index was calculated,left ventricular myocardial tissue was used for HE and Mason staining,apical myocardial tissue was used for electron microscopic specimen preparation,myocardial tissue structure was observed under-the microscope and collagen volume was calculated;some myocardial tissue was used to detect the expression of TGF-beta 1,Collagen I,VEGF protein and the expression of miR-200b gene by Western blot and Real-time PCR respectively.Result:(1)After 12 weeks of drug intervention,compared with the model group,the general condition was significantly improved,and their body weight was significantly increased(P<0.05),and their heart mass index was significantly decreased(P<0.05)of rats in the Compound Danshen Dropping Pill group;(2)After 12 weeks of drug intervention,compared with the model group,the glycometabolism indicators were not signifieantly changed(P>0.05)of rats in the Compound Danshen Dropping Pill group(P>0.05);the levels of triglyceride,total cholesterol and low density lipoprotein cholesterol were significantly decreased(P<0.05),and the level of high density lipoprotein cholesterol was significantly increased(P<0.05)in the lipid metabolism indicators of rats in the Compound Danshen Dropping Pill group;(3)After 12 weeks of drug intervention,compared with the model group,the activity of superoxide dismutase(SOD)was significantly increased(P<0.05)and the content of malondialdehyde(MDA)was significantly decreased(P<0.05)of rats in the compound Danshen dropping pill group;(4)After 12 weeks of drug intervention,compared with the model group,the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly decreased(P<0.05),the E/A ratio and left ventricular ejection fraction were significantly increased(P<0.05),and the left ventricular short axis shortening rate did not change significantly(P>0.05)of rats in the Compound Danshen Dropping Pill group;(5)After 12 weeks of drug intervention,compared with the model group,the results of staining and electron microscopy showed that the pathological changes of myocardial tissue and the volume fraction of myocardial collagen were significantly reduced(P<0.05)of rats in the compound Danshen dropping pill group;(6)After 12 weeks of drug inte.rvention,compare.d with t.he model group,the expression of TGF-beta l,Collagen I and vascular endothelial growth factor were significantly decreased(P<0.05)and the expression of miR-200b were significantly increased(P<0.05)in the myocardium of rats in the Compound Danshen Dropping Pill group.Conclusion:Compound Danshen Dropping Pills can protect the heart of type 2 diabetic rats by delaying myocardial f-ibrosis.Its mechanism may be related to regulating lipid metabolism and inhibiting lipid peroxidation,or to regulating "miR-200b/VEGF/TGF-beta 1" signal pathway. |
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