| Objectives Establish the streptozotocin-induced diabetic rat model to investigate the characteristics of inflammatory injury of diabetic cardiomyopathy,and to observe the protective effect on the diabetic cardiomyopathy and effect on the expression of TLR4/My D88 dependent signaling pathways of Shenshao decoction.Methods 50 SPF male Wistar rats were randomly divided into control group(n=10)and experimental group(n=40),the experimental group was used to induce diabetic rats model by high fat diet combined with low-dose streptozotocin(25mg/kg).The rats in control group was given the same dose citrate buffer solution.After the success of modeling,experimental group were randomly divided into five groups and treatment was given by daily gastric gavage for 10 weeks.The groups were diabetic cardiomyopathy group(DCM group,1ml/d saline),diabetes mellitus + low dose of Shenshao decoction group(DCM+LS group,4ml/d/kg Shenshao decoction),diabetes mellitus + middle dose Shenshao decoction group(DCM+MS group,8ml/kg/d Shen Shao decoction),diabetes mellitus + high dose of Shenshao decoction group(DCM+HS group,12ml/kg/d Shenshao decoction),group were gavaged with normal saline group,the control group was given saline to the dose 1ml/d.There were 10 rats in each group.The rats were added to the group if the group appear dead rats to ensure that each group was 10.At the end of the study,diastolic and systolic function in rats was measured by left ventricular catheterization.Then the rats were sacrificed and their myocardium were harvested.Hematoxylin eosin staining was used to observe the pathologic changes of myocardial morphology.Masson staining was applied to observed myocardial fibrosis.Ultrastructural changes of myocardium were observed by transmission electron microscope.Detection of CRP and IL-6 in rat myocardial tissue homogenate were by ELASE.Localization and quantitative expression of TLR4,My D88,TRAF6,NF-kappa B p65 were by immunohistochemistry and Western blot.The expression of TLR4/My D88 in myocardium was observed by confocal laser scanning microscope.Results 1 Compared with control group,the diabetic model group displayed severe hyperglycemia,decreased body weight and higher heart weight to body weight ratio;compared with DCM group,the level of blood glucose the weight and the ratio of heart weight to body weight in rats treated with Shenshao decoction decreased obviously;2 Compared with control group,the diastolic and systolic function of rats in diabetic model group was decreased,and Shenshao decoction treatment significantly improved heart dysfunction;3 Myocardial pathological structure injury obviously,myocardial tissue derangement,loose,necrosis,mitochondrial swelling,degeneration,myocardial fibrosis,Shenshao decoction treatment attenuated the injury mentioned above;4 Compared with the control group,the content of CRP and IL-6 in myocardial tissue of diabetic rats increased,suggesting that the myocardial tissue of diabetic rats appeared obvious inflammatory reaction,Shenshao decoction intervention decreased the indicators compared to the model group rats;5 Compared with the control group,the expression of TLR4,My D88,TRAF6,NF-kappa B p65 increased significantly in diabetic model group,laser scanning confocal microscopy showed TLR4 and My D88 co-expression in myocardial tissue,after the intervention of Shenshao decoction,The expression of these factors decreased.Conclusions 1 TLR4/MyD88 dependent signaling pathway is involved in the occurrence and development of the inflammatory injury in diabetic cardiomyopathy;2 Shenshao decoction can inhibit the TLR4/My D88 dependent signaling pathway,reduce inflammatory damage of myocardium,improve cardiac function,and reduce the pathological injury and fibrosis of myocardium in diabetic cardiomyopathy rats,Shenshao decoction has a protective effect on myocardial tissue. |
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