The Effect And Mechanism Of Telmisartan On The Kidney Of Rats Fed With Long-term HSHF Diet

Objective:1.To observe the effect on the renal morphology of rats fed with long-term HSHF diet after the intervention of telmisartan.2.To observe the effect of telmisartan on the number and polarization of macrophages in the kidney of rats fed with long-term HSHF diet, to investigate whether telmisartan can through this way to play the protective effects on the kidney early.Methods:32 healthy male SD rats(6-8 weeks of age) were randomly divided into two groups after adaptive feeding for 1 weeks, normal control group, 8 rats;high sugar and high fat group(HSHF group),24 rats.After feeding 6 months,HSHF group were randomly assigned to three subgroups: group HSHF, 8 rats; telmisartan group, 8 rats; HSHF control group.Normal group was fed with normal diet;HSHF group was fed with high sugar and high fat diet(Feed formula: 70% ordinary feed +20% lard +10% sucrose +1% cholesterol +0.25%acid);telmisartan group was fed with high sugar and high fat diet and telmisartan 5mg/kg.d irrigation stomach;HSHF control group was fed with high sugar and high fat diet and given such as volume of physiological saline.3 months after the intervention of telmisartan, rats fasted 8 hours, intraperitoneal injection of urethane(4ml/kg) anesthesia, after death under aseptic conditions to removal of double renal tissue. The left kidney was fixed with 10% neutral formalin for PAS staining and immunohistochemistry, and the right kidney was placed in liquid nitrogen for Western Blot detection. Renal pathological changes were observed under light microscope with PAS staining, the expression of CD68+ in renal tissue was detected byimmunohistochemical method.The expression level of podocin and M1 and M2 macrophage specific marker i NOS and Arg-1 protein was detected by Western Blot.Results:1.After HSHF meal feeding 9 months,compared with the normal control group,HSHF group of the number of CD68+ macrophage infiltration in the kidney was significantly increased,and the glomerular mesangial matrix was significantly increased;podocin protein and Arg-1 protein expression decreased significantly,i NOS protein expression increased significantly, the difference was statistically significant(p<0.05).2.After HSHF meal feeding 9 months,compared with the HSHF group,HSHF control group of the number of CD68+ macrophage infiltration in the kidney,the glomerular mesangial matrix,podocin protein,Arg-1 protein and i NOS protein expression no change, the difference no statistical significance(p > 0.05).3.After the intervention of telmisartan 3 months,compared to the HSHF control group,telmisartan group rat kidney CD68 + macrophages infiltration quantity decreased,mesangial matrix proliferation degree reduced;podocin protein and Arg-1 protein expression increased significantly,i NOS protein expression level was significantly reduced, the difference has statistical significance(p < 0.05).Conclusions:1.Telmisartan can reduce the number of macrophages in the kidney of the rat with long-term HSHF diet, reduce glomerular mesangial matrix proliferation, protecting podocytes.2.Telmisartan has ability to regulate renal macrophage polarization, and plays an important role in the renal protective effect through inhibition of M1 macrophages activation enhanced M2 macrophage activation.