Study The Effects And Mechanisms Of Atorvastatin And Shenshao Oral Liquid On Diabetic Cardiomyopathy

Objectives Through observation of the expression of TLR4, NF kappa B p65, IL-6 and TGF-?1 in myocardial tissue and discussion on the effect of atorvastatin and Shenshao oral liquid on TLR4-NF-?B inflammatory signaling pathway and the protection on diabetic cardiomyopathy rat.Methods 50 healthy rats were randomly divided into the control group(Sham, n=8) and the experimental group(n=42). Control group(Sham, n=8) given normal diet and the experimental group(Test, n=42) given high fat diet. After 4 weeks of feeding, rats in the experimental group using small dose of streptozotocin(STZ, 25mg/kg) was administered intraperitoneally to damage part of islet ? cells, making rat model of type 2 diabetes.Respectively after STZ injection 3d, 7d measured fasting blood glucose(Fasting plasma glucose, FBG), the experimental group who is greater than 16.7mmol/L at two times entered the stage drug intervention. Diabetic rats successfully screened arbitrary were grouped into Model group, Atorvastation group, Shenshao oral liquid group and Combined group. Atorvastatin group rats according to 1mg/00g/d by intragastric administration,Shenshao oral liquid group in accordance with the 25mg/100g/d intragastric administration,the combined group given atorvastatin at the dose of 1mg/100g/d, again according to the dose 25mg/100g/d gave Shenshao oral liquid, 1ml distilled water was given in control group and model group,gavage for 8 weeks. In the whole experiment, the body weight, the changes in blood glucose, and the spirit of the general status was recorded, rat serum biochemical detection; Ventricular cannulation was used to assess the cardiac functions.HE staining,electron microscope and Masson staining were used to observe the morphological changes of myocardial cells and interstitial, and the ultrastructural changes of the myocardium were observed under the electron microscope. The expression levels of TLR4, NF-?B, IL-6 and TGF-?1 in the cardiac tissues were determined by Western blotting and Immunohistochemistry.Results 1 Before STZ injection(0-5W), each rat food,water, mental state and activities were normal. In the control group, the weight rises gradually, the normal blood glucose;the experimental group rats fed with high fat diet, body weight increased rapidly compared with the control group(sham group), but there was no statistical significance, blood glucose was normal or elevated, compared with the control group(sham group), not statistically significant. After STZ(6-16W), Control group(sham group) was normal growth, smooth hair Shaishun; the experimental group rats had more to drink, polyphagia,polyuria, and the gradual emergence of listlessness, weight loss(P<0.05), blood glucose increased(P<0.05), the effect of Atorvastatin and Shenshao oral liquid intervention, blood glucose change obviously, and maintain high level. 2 Biochemical indicators of detection,Compared with the Sham, the TC, TG, LDL significantly increased(P<0.05), HDL was significantly decreased in DCM group(P<0.05), the DCM+AT, and DCM+AT+SH have significantly reduced TC, TG, LDL(P<0.05), HDL did not change significantly, and there was no statistical significanceand; compared with DCM group, TC, TG, LDL, HDL was not statistically significant in the DCM+SH. Compared with Sham group, CK-MB and CRP in DCM group were significantly higher(P<0.05), the DCM+AT, the DCM+ SH and the DCM+AT+SH were lower than DCM group(P<0.05), and the DCM+AT+SH was significantly lower than the former two groups(P<0.05). 3 Ventricular weight/body weight ratio(HW/BW), left ventricular weight/body weight(LVW/BW) in the DCM group was significantly higher than Sham group rats(P<0.05), DCM+SH group, DCM+AT group and DCM+AT+SH group was significantly decreased(P<0.05), and DCM+AT+SH group were lower than the monotherapy group(DCM+SH, DCM+AT)(P<0.05). 4 Pathological observation, compared with the sham roup, myocardial fiber fracture, distortion, interstitial hyperplasia, inflammatory cell infiltration, collagen deposition, myocardial nuclei disappear, solid dye, nuclear staining chromatin, mitochondria into vacuole, visible glycogen lipid particles in DCM group, etl. The above changes were attenuated in DCM+SH, DCM+AT and DCM+AT+SH, and the DCM+AT+SH is more obvious compared to that of the single drug group. 5 Heart function test, compared with the Sham group, DCM myocardial left ventricular end-diastolic pressure(Left ventricular enddiastolic pressure, LVEDP) significantly increased(P<0.05), DCM+AT and DCM+AT+SH group LVEDP were lower(P<0.05), and DCM+AT+SH group reduced more significantly(P<0.05),There was no significant change of LVEDP in DCM+SH group.Left ventricular systolic pressure(Left ventricular systolic pressure, LVSP) and left ventricular pressure increase or decrease the maximum speed(Left ventricular pressure rise or fall a maximum speed, ±d P/dtmax) was not statistically significant in rats. 6Immunohistochemistry and Western blot display, Compared with control group, The expression levels of TLR4, NF-?B, IL-6 and TGF-?1 in the cardiac tissues significantly increased in model group(P<0.05), which was decreased in DCM+AT and DCM+AT+SH group as compared with model group(P<0.05), while Combined group decreased more significantly. Compared with the DCM group, NF-?Bp65, IL-6, TGF-?1 expression decreased in DCM + SH group, TLR4 was no significant change.Conclusions1) Atorvastatin has protective effect of lipid-lowering, anti-myocardial fibrosis, reduce LVEDP on myocardial injury in DCM by down-regulating TLR4/NF-?B inflammatory pathways;2) Shenshao oral liquid has protective effect of anti-myocardial fibrosis on myocardial injury in DCM by down-regulating NF-?B inflammatory pathways;3) Two-drug combination therapy has more significant improvement on myocardial injury,and there is a synergistic effect.