An Experimental Study On He Cardiac Protective Effects Of Telmisartan On Diabetic Cardiomyopathy In Rats

Aim To investigate cardiac protective effects and its possible mechanism of telmisartan on diabetic cardiomyopathic rats;and to explore the effects of telmisartan on expression of NF-κB, ICAM-1 and MCP-1 in the myocardium of diabetic cardiomyopathic rats and its possible cardiac protective effects mechanisms.Methods Studies were done in 42 male Sprague-Dawlay rats weighing 180-200g. Of these, 30 rats received a single intraperitoneal injection of STZ (55mg/kg) dissolved in sodium citrate buffer, and the remaining rats received an injection of buffer and served as nondiabetic controls (group C, n=12). After 4 weeks later, the cardiac muscle ultramicrostructure changes accords with the diabetic cardiomyopathy's, indicating that diabetic cardiomyopathy models were established. The diabetic cardiomyopathy rats were randomly divided into following 2 groups: untreated DCM rats (group DCM, n=12), DCM rats treated with Telmisartan [20mg/(kg·d)] for 8 weeks(group T, n=12).At the end of the experiment, LVMI and heart function were detected and the cardiac muscle ultrastructure was observed to investigate cardiac-protective effects of telmisartan on diabetic cardiomyopathy rats. Immunohistochemical techniques were used to detect NF-κB activation , ICAM-1,MCP-1 expression.Results After 8-week telmisartan treatment, the levels of LVMI, LVEDP , t-dp/dt was increased markedly(all p<0.05). Compared with starch group, while LVSP , +dp/dt_max , -dp/dt_max was decreased markedly(all p<0.05).Rarefaction, fragmentation, derangement of myocardium myofibril, proliferation, tumefaction, degeneration of mitochondria, disruption, rarefaction of mitochondrion ridge, deposition of glycogen, hyperplasia of collagen in interstitial were observed under electron microscope. All the above changes in the telmisartan group diabetic rats were less obvious. And the control rats showed no difference. Telmisartan down regulated NF-κB, ICAM-1 and MCP-1 expression in the cardiac muscle.Conclusions: 1. Telmisartan can improve heart function, and the myocardium tissue pathogenetic constitution and ultramicrostructure changes in diabetic cardiomyopathic rats. 2. The cardio-protective effects are intimately related with inhibition of NF-κB activation. Inhibition of NF-κB activation may be one of the potential mechanisms of decreased ICAM-1,MCP-1 expression, which leads to the decreased the transformation and secretion of myofibroblasts. All of those may make extracellular matrix growth downwards.