Renal Protective Effects And Mechanisms Of New Drug TJO711on Renovascular Hypertensive Rats

Objective To investigate the renal protective effects and mechanisms of new drug-TJ0711on the rats model of two-kidney, one-clip hypertension.Methods Thirty six of Wistar rats were randomly divided into six groups: shamgroup and five groups of two-kidney, one-clip renovascular hypertension. And thesefive groups were divided into model group, carvedilol group, lower-TJ0711group,modest-TJ0711group and higher-TJ0711group with6rats in each group. Delivery8weeks later the rats were sacrificed and urea nitrogen,creatinine,urine protein/urine creatinine ratio and serum NO were examined. The clip side renal cortical tissueof rats were collected which were stained for PAS and Masson. The expression ofeNOS, HIF-1α and Vasohibin were examined from renal cortical tissue forimmunohistochemical staining and western blot.Results Compared with the model group, the treatment groups rat kidneymorphology and serum creatinine did not change significantly, but serum ureanitrogen and urine protein/urine creatinine ratio levels decreased significantly, whileserum NO and the expression of eNOS protein were increased (P<0.05). Immunohistochemistry and Western blot showed that the expression of HIF-1α andVasohibin were downregulated in lower-TJ0711and modest-TJ0711compared withmodel group(P<0.05). However, Carvedilol group and higher-TJ0711group showedno significant change in the expression of HIF-1α and Vasohibin (P>0.05).Conclusion: HIF-1α and Vasohibin protein were upregulated while eNOS proteindownregulated in the rats model of two-kidney, one-clip hypertension. New TJ0711can significantly decrease serum urea nitrogen and urine protein/urine creatinine ratiolevels and the mechanism of its renal protective effects on renovascular hypertensiverats may be assotciated with upregulation of eNOS expression, increase of NO levelsand downregulation of HIF-1alpha and Vasohibinexpression.