| Objective:Many researches have shown that the occurrence of myocardial injury in diabetic cardiomyopathy has multiple factors,the activation of renin-angiotensin aldosterone system and inflammatory factors play an important role in it.P38 mitogen-activated protein kinase is related to myocardial fibrosis,and can influence the process of diabetic cardiomyopathy by regulating the expression of nuclear transcription factor- κ B.Current researches show that AngⅡand its specificity type 1 receptor AT1 R mediate RAAS.When AngⅡactivates AT1 R of the myocardial cell membrane,the expression of p38 MAPK up-regulated,which can accelerate myocardial fibrosis process;P38MAPK regulates gene transcription of inflammatory factors, and aggravates myocardial inflammatory injury by activating the downstream of nuclear transcription factor-κB.In order to truly improve the prognosis of diabetic cardiomyopathy and the quality of life,the development for the medicine of diabetic cardiomyopathy is very important.Shenshao Decoction(formerly known as herbal compound Kuanxin) is Chinese herbal medicine compound preparation that based on Shaoyaogancao decoction that can treat various inflammatory pains and traditional prescription Danshen soup that can treate chest stuffiness,it can improve the myocardial fibrosis of acute ischemia-reperfusion injury.Our teams’ early research has shown that Shenshao Decoction can improve myocardial fibrosis and inflammatory damage caused by acute myocarditis.Based on these discoveries,the purpose of this study is to disscus whether Shenshao Decoction can improve myocardial fibrosis and inflammatory damage by adjusting Ang Ⅱ /p38MAPK/NF- κ B pathway in diabetic cardiomyopathy.At the same time this research can find the related molecular biological basis for traditional Chinese medicine theory,and provide measurable indicators of myocardial damage to diagnose and relieve diabetes earlier.Method:1 Grouping:Forty specific pathogen free male Wistar rats(170-200g) were fed in SPF animal laboratory one week and were randomized into five groups: a control group,a model group,a low does of Shenshao Decoction group,a moderate does of Shenshao Decoction group and a high does of Shenshao Decoction group.Each group has eight rats.Before modeling,the control group was fed with normal diet for four weeks,the model group,the low does of Shenshao Decoction group,the moderate does of Shenshao Decoction group and the high does of Shenshao Decoction group with a high-fat diet for four weeks.2 Molding:The model group,the low does of Shenshao Decoction group,the moderate does of Shenshao Decoction group and the high does of Shenshao Decoction group were induced by intraperitoneal injection of STZ(25mg/kg).After STZ administration, rats with fasting blood glucose≥16.7 mmol/L in two consecutive analyses and drinking more, polyuria, polyphagia were considered the diabetic rat model.The control group injected intraperitoneally the same dose of citrate buffer. After modeling,the control group was fed with normal diet for twelve weeks,and the model group,the low does of Shenshao Decoction group,the moderate does of Shenshao Decoction group and the high does of Shenshao Decoction group with a high-fat diet for twelve weeks.3 Drugs and treatment:Rats in low,moderate and high dose of Shenshao Decoction group were respectively given Shenshao Decoction at the does of 125,250,500 mg /kg?d through intragastric administration.The control group and model group were all given the same dose of distilled water,all groups were administrated for twelve weeks.4 When rats were all killed,the left ventriculars were taken for experiment.Cardiac pathological changes were used with hematoxylin-eosin staining,the myocardial collagen volume fraction was calculated by Masson methods.Enzyme-linked Immunosorbent Assay method was used to calculate expressions of angiotensin II in myocardial tissue.Immunohistochemical method was used to observe expressions of angiotensin II,angiotensin type 1 receptor,nuclear transcription factor- κ B,and tumor necrosis factor- α in myocardial tissue.Western blot was used to detect expressions of p38 mitogen-activated protein kinase and p-p38 mitogen-activated protein kinase in myocardial tissue.Result: 1 The results on drug action 1.1 Physiological and pathological changes in model group rats:The model group appeared depressed,water increased,urine volume increased,less body,hair luster and weight loss.Pathological damage occured obviously in DCM rats. 1.2 The results on hypoglycemic effect and the protection of the heart:①Compared with model group,the body weight of low,moderate and high dose of Shenshao Decoction group was increased,the differences had statistical significance(P<0.05);Compared with model group,the heart weight/body weight of low,moderate and high dose of Shenshao Decoction group was decreased,the differences had statistical significance(P<0.05);Compared with model group,the left ventricular weight index of low,moderate and high dose of Shenshao Decoction group was decreased,the differences had statistical significance(P<0.05).②Compared with model group,the fasting blood glucose of low,moderate and high dose of Shenshao Decoction group was decreased, with statistical significance(P<0.05).High-dose group decreased more obviously(P<0.05).③Improving the myocardial pathological damage: Masson staining observed myocardial fibrosis degree in low,moderate and high dose of Shenshao Decoction group was improved.Compared with model group,the CVF of low,moderate and high dose of Shenshao Decoction group was increased,the differences had statistical significance(P<0.05),high-dose group decreased more obviously(P<0.05). 2 The results on mechanism of the protection of the heart 2.1 The mechanism on DCM ratsThe study found that the DCM rats were:①RAAS active substances increased:the content of AngⅡin myocardial tissue of low,moderate and high dose of Shenshao Decoction group was increased,compared with the control group,the difference had statistical significance. ② The myocardial inflammatory reaction increased:the expression of angiotensin II,angiotensin type1 receptor,p-p38 MAPK protein,nuclear transcription factor-κB protein and tumor necrosis factor-αof myocardial tissue in model group were all increased,compared with the control group,the difference had statistical significance(P<0.05). 2.2 The mechanisms of Shenshao Decoction on the myocardial fibrosis and inflammatory damage in DCM rats.Shenshao Decoction could reverse the myocardial fibrosis and inflammatory damage in DCM rats:①Suppressed RAAS active substances:the content of AngⅡin myocardial tissue of low,moderate and high dose of Shenshao Decoction group was decreased,compared with the model group,the difference had statistical significance②The myocardial inflammatory reaction was suppressed : the expression of angiotensin II,angiotensin type1 receptor,p-p38 MAPK protein,nuclear transcription factor- κ B protein and tumor necrosis factor- α of myocardial tissue in model group were all suppressed,compared with the model group,the difference had statistical significance(P<0.05).Conclusion:1 Shenshao Decoction can alleviate diabetic myocardial fibrosis and inflammatory damage of DCM rats,and there is dose-dependent relationship among125, 250and500mg·kg-1 dose;2 Mechanisms of Shenshao Decoction on alleviating diabetic myocardial fibrosis are based on decreasing the content of AngⅡ;3 Mechanisms of Shenshao Decoction on alleviating diabetic myocardial inflammatory damage are based on decreasing the content of TNF-α;4 The mechanisms of Shenshao Decoction on the myocardial fibrosis and inflammatory damage are related with adjusting AngⅡ/p38MAPK/NF-κB pathway. |
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