Effect Of Telmisartan On Renal Microvascular Disease In Diabetic Rats Induced By Serum MCP-1

Objecttives: Monocyte chemoattractant protein-1 (MCP-1) is a regulator of monocyte/macrophage migration and infiltration of the most important inflammatory chemokine. It could increase vascular endothelial injury through the expression of MCP-1,also induce vascular smooth muscel cell proliferation and migration. The formation of high glycation end product (AGE) in long-term high blood sugar and diabetic state, nitric oxide (NO) synthesis may be reduced or decreased activity to increase MCP-1 expression. MCP-1 may lead to endothelial dysfunction and induce vascular smooth muscle cell proliferation or migration which aggravate atherosclerotic lesions. In our experiment, our research was based on diabetic OLETF (otsuka long-evans tokushima fatty) nephropathy rats and the department of LETO control rats:Effect of telmisartan on renal microvascular disease in diabetic rats induced by serum MCP-1.Methods:Otsuka, Japan Insitute supplied 24 male OLETE rats and the fellow 10 male LETO normal non-diabetic control group rats which were 4-week old. All rats are off weight 150-200g. The male OLETF rats were fed with high-fat diet and the male LETO control group rats were always fed with normal diet. All rats were divided into four groups according to different treatment:24 male OLETF diabetic rats were randomly divided into three groups, telmisartangroup(MT),the metformin group(MET),the model without making intervention group(MX)and without intervention of normal non-diabetic control group(NC). All rats were sacrificed after fasting for 12 hours, Centrifugalled separation of serum and renal tissue. MCP-1,FFA,FINS,FBG,TC,TG,LDL,HDL,BUN,Scr and 24h urine protein level in plasma were measured. The glomerular filtration membrane of the ultrastructures in all rats were observed by the transmission electron microscopy. MCP-1 expression levels of renal vascular endothelial tissue were detected by immunohistochemistry. HOMA-IRI=(FINS×FBG)÷22.5.Four groups were compared between the above indicators, also compared the MCP-1 with FFA,FINS,FBG,TC,TG,LDL,HDL correlation between biochemical indicators. Results:1. Serum MCP-1 levels among groups:Compared with the control group [(30.91±4.42)pg/ml], the serum MCP-1 levels in diabetics model group [(44.92±7.21)pg/ml] increased (P<0.05); Compared with drug intervention telmisartan group [(32.70±6.71)pg/ml],metformin group [(33.33±4.47)pg/ml], the serum MCP-1 levels in diabetics model group [(44.92±7.21)pg/ml] increased (P＜0.05).2. Correlation analysis:Linear correlation ananlysis showed that serum MCP-1 levels had positive relationship with the levels FFA,TC,TG,LDL,FINS,HOMA-IR. (r,p 0.454,0.040;0.315,0.040;0.292,0.046;0.418,0.007;0.360,0.022;0.527,0.001)3. Electron microscopy features of renal vascular endothelium:The glomerular filtration membrane disease of the telmisartan group and other two groups rats are improved better than the model group; observed small vascular endothelial proliferation, mild basement membrane thickening, near normal foot progress, nucleus, mitochondria, endoplasmic reticulum structure.Conclusions:We successfully got the diabetic OLETF rats with renal vascular endothelial dysfunction model through high diet. Blood monocyte chemoattractant protein-1 (MCP-1) expression increased greatly in diabetic OLETF male rats. It also involved in the pathogenesis of disease in glomerular filtration module, and MCP-1 expression correlates positives with glomerular filtration mold disease. Renin-angiotensin system (RAS) blockers telmisartan could inhibit the inflammatory response, decrease MCP-1 expression improve blood lipids and insulin resistance; thus protected glomerular flitration membrane of renal microvascular damaga.