Effect of intragastric administration of benazepril on expression of connectin in diabetic nephropathy rats
Objective To investigate the effect of benazepril on the expression of connexins(Cxs)in the renal tis-sues of diabetic nephropathy rats and its possible mechanism.Methods The SD male rats were divided into the control group,diabetes group,and intervention group.Rats in the diabetes group and intervention group were injected with STZ 65 mg/kg into the left lower abdomen once to establish the I-type diabetes models.Rats in the control group were injected with the same dose of citric acid buffer intraperitoneally.After the models were successfully established on the second day,rats in the intervention group were given benazepril 10 mg/(kg·d)by gavage daily at a fixed time,while rats in the control group and diabetes group were given the same volume of 0.9%sodium chloride solution.The treatment lasted for 8 weeks,during which,the body weight of each group was measured,fasting blood glucose was detected by enzymatic electrolytic chromatography,urinary microalbumin was detected by double-antibody sandwich method,and serum creatinine and urea were detected by sarcosine oxidase method and enzyme-coupled rate method,respectively.After 8 weeks,the rats were eu-thanized,and the distribution of connexin Cx37,Cx40,and Cx43 in the renal pathological tissues was observed by SABC method.The expression of connexin Cx37,Cx40,and Cx43 was detected by immunohistochemistry,and the expression of connexin Cx37,Cx40,and Cx43 mRNA was detected by RT-qRCR.Results Compared with the control group,the body weight of the diabetes group and the intervention group decreased significantly(P<0.05),and the blood glucose lev-el increased significantly(P<0.05);the blood urea nitrogen,blood creatinine,and urinary microalbuminuria of the inter-vention group were significantly lower than those of the diabetes group(all P<0.05).In the diabetes group,the distribu-tion of Cx37 and Cx43 in the efferent arterioles,afferent arterioles and proximal renal tubules was significantly weakened.In the intervention group,the expression of Cx37 and Cx43 in the proximal renal tubules significantly increased.In the dia-betes group,the distribution of Cx40 in multiple afferent arterioles and the macula densa was significantly weakened,and the distribution of Cx40 in the macula densa was enhanced in the intervention group.Compared with the diabetes group,the expression levels of Cx37 and Cx40 in the intervention group increased,with statistically significant differences(both P<0.05).The expression of Cx43 in the intervention group was higher than that of the diabetes group,but the difference was not statistically significant(P<0.05).The CT value of Cx37 in the diabetes group was significantly higher,and the Cx37 CT value in the intervention group was smaller than that of the control group(P<0.05).The CT value of Cx40 in the control group was not significantly different from those of the diabetes group and the intervention group,while the Cx40 CT value in the intervention group was significantly smaller than that of the diabetes group(all P<0.05).Compared with the control group,the Cx43 CT value in the diabetes group significantly decreased,and the Cx43 CT value in the intervention group significantly increased,and significant difference was found in the Cx43 CT value among all groups.Conclusion Benazepril can up-regulate the expression of renal connexin proteins in diabetic nephropathy rats,alleviate the pathological damage,protect the kidneys,and delay the progression of the disease.