Changes And Analysis Of TRPC6Expression In STZ-induced Diabetic Rat Kidney

Objective: To Analysis and explore the role of TRPC6in thepathogenesis of proteinuria in diabetic kidney disease by observation theexpression of the TRPC6in the kidney of diabetic rats.Methods:135male SD rats were randomly divided into control group(n=25) and experimental group (n=110). Experimental group were treatedwith intraperitoneal injection of STZ65mg/kg once to establish the model ofDM. After the injection of STZ, not model rats were removed from theexperimental group, the others were included in the DM model group. Rats ofall groups were killed at the time point of2w、4w、8w、12w and16w,respectively. The level of the body weight(BW)、fasting blood glucose(FBG)、urine glucose（UG）、24-hour urine protein（UP）、renal function、liver function and kidney hypertrophy index（KHI）were monitored in eachgroup. Kidney pathological changes of rats of all groups were observed by thestaining of hematoxylin-eosin (HE). Glomerular basement membranes of allgroups were observed by the transmission electron microscopy to learnwhether they were thickened or the degree of the thickening and whether thepodocytes were falled off or fused. TRPC6expression sites and theexpression changes with the time point were observed byimmunohistochemical methods. Results: The rat model of DM can be createdby a single intraperitoneal injection of STZ, the rate of developed model ofDM was59%, the mortality rate was43%. Compared with the control group,the food intake、water intake、urine output、FPG、24-h UP、KHI、average foot process width（AFPW)、foot process fusion rate (FPFR)、averagethickness of GBM、the mean optical density(MOD) of TRPC6expressionvalues and kidney damage ratings were significantly increased, total protein、albumin and glomerular podocyte number were significantly reduced（p＜0.05）. Within all time points of the model group，24-h UP、AFPW、FPFR、average thickness of GBM、MOD value and kidney injury score weregradually increased, the total protein、albumin、KHI and podocyte numberwere gradually decreased with the extension of the modeling time(p<0.05),while the difference of the food intake、water intake、urine output and FPGwith the extension of the modeling time were not statisticallysignificant(p>0.05). Compared with the control group, the level of creatinineand blood urea nitrogen of the time point of8w、12w and16w in model groupwere significantly higher and gradually increased with the extension ofmodeling time（p＜0.05）. The body weight of rats in the model group weresignificantly lower compared with that of the control group（p＜0.05）;Moreover, the body weight of model group were lower compared with that ofbefore the model at the time of8week before, and the body weight weresubsequently increased（p＜0.05）. The expression of TRPC6in DM rats waspositively correlated with the level of creatinine（r=0.580，p＜0.002）、thelevel of urea nitrogen（r=0.592，p＜0.002）、the level of urine protein（r=0.725，p＜0.001）and kidney injury score（r=0.688，p＜0.001）.Whilethe expression of TRPC6in DM rats was negatively correlated with thenumber of podocytes（r=-0.594，p＜0.002）.Conclusions: High expression of TRPC6in the rat model of DM glomerulus can be induced by hyperglycemia. High expression of TRPC6inthe rat model of DM glomerulus may be involved in the formation ofpodocyte damage and proteinuria.