The Experimental Study Of The Effects Of TASAE On The Diabetic Cardiomyopathy And Nephropathy In Rats During The Early Stages

Diabetic cardiomyopathy (DCM) have a special relationship with high blood glucose, the decrease of left ventricle diastolic function is the main representation in early stage, and also the decrease of left ventricle systolic function would appeared accompanying with time going on, the heart failure would happened in the end. The structural changes show that the accumulation of extracellular matrix and the reconstitution of myocardial interstitium, the pathogenesis of DCM is very complicated. Besides the myocardial fibrosis, the decreased cardiac function is also related to the functions of membrane channel protein, Sarco endo reticulum calcium ATPase. Total arasolides of aralia elata (TASAE) have the function of mitigating myocardial ischemia, improving the activity of antioxidases. But the effects of TASAE on diabetic rats hearts in the early stage has not been reported yet. Meanwhile the effects of TASAE on diabetic rat's 24h urine microalbumin and renal cortex structure were studied.Objectives:1. To observe the effects of TASAE on the hemodynamic parameters, L type calcium channel currents (ICa-L), transient outward potassium currents (Ito), TGF-β1 CTGF proteins and structures changes in diabetic rat heart during the early stages.2. To observe the effects of TASAE on renal function, 24h urine microalbumin, TGF-β1 CTGF protein and structures changes in diabetic rat kidney during the early stages .Methods:The hemodynamic parameters were detested by biological function system, ICa-L and Ito were detested by patch clamp technics and the TGF-β1 CTGF were detested by immunohistochemistry methods and ultrostructures were observed by electron microscope.Results:1. Compares with group C, LVEDP were increased and the absolute value of±dp/dtmax were decreased in group M (P<0.05). but the TASAE groups were improved (p<0.05, p<0.01); TASAE can also increase the ICa-L (P<0.01) but no effect on Ito (P<0.05), meanwhile, It can decrease the TGF-β1 and CTGF proteins expression in diabetic rat heart (P<0.01), TASAE can protect cardiac ultrostructure from damaging in early stage.2. In group M, relative kidney weight/body weight ratio and 24h urine microalbumin were increased (p<0.05), TGF-β1 and CTGF proteins expression also increased (p<0.05,p<0.01) but they were decreased in TASAE groups (p<0.05). The quantity of mesangium increased under optical microscope and glomerular basement membrane became thicken under electron microscope in group M, but they were better in TASAE group.Conclusions:1.It was discovered that different pathological changes in diabetic heart and kidney at high blood glucose state by observations of morphalogical changes and hemodynamic parameters, it showed that the models of diabetic cardiomyopathy and nephropathy were sucessed.2.It was observed that L-type calcium currents is decreased in early diabetic cardiomyocyte and TASAE can increase it,It was proved they are L-type calcium currents by Verapail and submit dose dependent.3.It was found that diastolic function is declined at 4 weeks and both systolic and diastolic function decreased at 8 weeks,TASAE can improve it through L-type calcium currents ,also submit dose dependent. 4.Persistent high blood glucose state can improve the TGF-β1,CTGF protein expression in diabetic heart and kidney during the early stage,TASAE can inhibit it and protect the structural integrity.5.TASAE can protect the structure of diabetic myocardium and glomerular basement membrane,lower the quantity of 24h urine microalbumin. According to the results, we suggested that they may have the common protective mechanism on diabetic heart and kidney by TASAE through inhibiting the TGF-β1,CTGF protein expression.