The Experimental Study On Protective Effects And Inlfammation Mechanisms Of Sankudiwan On Myocaridial Ischemia In Rats

The injury of myocardial ischemia is a complex pathological mechanism which linked tomany factors. Recently research showed that the surge of inflammatory cytokines play animportant role in the process of myocardial ischemia, myocardial ischemia is the result ofboth system inflammatory reaction and local inflammatory reaction, and the over expressionof inflammatory reaction is one of the most important mechanisms of myocardial ischemia.As the key of pathology of myocardial ischemia, the signal transduction pathway of NF-kappaB participated in all kinds of physiology and pathology like cell proliferation, inflammation,apoptosis, and so on. Therefore, to study the mechanism of antagonism to myocardialischemia in experimental rats and provide the evidence of clinical efficacy for sankudiwan,this study used sankudiwan as the research medicine and focused on the antagonist ofinflammation over expression in myocardial injury, also the NF-kappa B signal transductionpathways.Purpose: This study sought to present the mechanism of sankudiwan in antagonism tomyocardial ischemia and related inflammatory reaction in experimental rats.Method:Using modern scientific technology to study Wistar rats,including pharmacy,pharmacology and phathology.The healthy Wistar rats were divited into normal control,negative control,danshendiwan positive control and sankudiwan high, medium,low dosagegroup. The myocardial ischemia rats model were made by intraperitoneal injection ofhydrochloric acid isoproterenol for three days. After the therapy of myocardial ischemiarats,we can observed the electrocardiogram change and the concentration of serum cardiactroponin I, CK, CK-MB, as well as the myocardial inflammation under electron microscop.Using the ELISA methord, we can observed the concentration of plasma TNF,IL1,IL6andvascular cell adhesion factor1.Also, we can detected the1κ B-alpha in myocardialcell,NF-kappa B activity, the NF-kappa B p65mRNA gene expression, the N-kappa B p65protein expression by Western-Blot, electrophoresis migration rate (EMSA), RT-PCR,immunohistochemical method,respectively.This study sought to present the mechanism ofsankudiwan in antagonism to myocardial ischemia. Result:1.Sankudiwan has obvious does-dependent effect on model ratsS-T segment deviation,incidence of myocardial ischemia,CK, CK-MB and CTN, especially the sankudiwan high,low group, and the effect is better than danshendiwan.2. Sankudiwan can obviously improve the micro-struture and ultra micro-structure onmodel rats,especialy the sankudiwan high and medium groups, and the effect is better thandanshendiwan group. Which indicated that sankudiwan can protect the cardiac muscleorganize.3．Sankudiwan may decrease the release of IL-1, IL-6,TNF-α, Vascular cell adhesionfactor-1, especially the SK high, medium group, and the effect is better than danshendiwa.4．sankudiwan may upregulate the expression of1κB-α in myocardial cell cytoplasm,decrease the activity of NF-κB, restrain the nf-kappa Bp65mRNA gene and the nf-kappaBp65protein expression, especially the SK high, medium group, and the effect is better thandanshendiwa.Conclusion: Sankudiwan has effective anti-myocadrial ischemia function.Themechanism relate to inhibiting the activity of NF-κB,upregulating the expression of1κB-αand then decrease the release of IL-1, IL-6,TNF-α,Vascular cell adhesion factor-1,which can protect myocardial cells,resistance of myocardial ischemia injury through a varietyof comprehensive mechanism.