ABSTRACT
Objective:To study the effect of icariin on renin homologous protein A (RhoA)/Rho-related kinase (ROCK) pathway in rats with nephrotic syndrome (NS) and its protective mechanism. Method:Totally 54 clean-grade male SD rats were tested and randomly divided into normal group, model group, RhoA inhibitor group (Rhosin, 40 mg·kg-1·d-1) and three doses of icariin groups (low, medium and high corresponding dose， 30, 60, 120 mg·kg-1·d-1). Adriamycin hydrochloride 6.5 mg·kg-1 was given in tail vein of rats to induce NS model in rats. After the model was established, peritoneal administration was carried out. The normal group and the model group were given saline 2.5 mL·d-1, and the inhibitor group and all of dose groups were given corresponding doses of Rhosin and icariin for intervention. Total urinary protein (Alb), creatinine (Cre), total urinary protein/creatinine ratio (A/C) kit were detected in rats, ultrastructure of kidney was identified by transmission electron microscopy (TEM), and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and proteins expressions of RhoA, ROCK1, ROCK2. Result:TEM showed that the basement membrane was intact and the foot process was regular in the normal group, in model group, basement membrane was damaged seriously, foot process disappeared, and fusion was serious, in the low-dose group, the basement membrane injury was alleviated, the number and density of foot process were improved, and the fusion was obvious， in the middle-dose group and the inhibitor group, the basement membrane thickening was alleviated, and the foot process was slightly fused, in the high-dose group, the basement membrane structure was more complete, and podocytes were longer and arranged tightly. Compared with the normal group, the levels of Alb, Cre and A/C in urine, and RhoA, ROCK1 and ROCK2 mRNA and protein expressions in kidney tissue of rats of the model group were significantly higher (P<0.05). Compared with model group, the levels of Alb, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the inhibitor group and low, medium and high-dose groups, and Cre in urine in inhibitor group and high-dose group decreased significantly (P<0.05). Compared with the inhibitor group, the levels of Alb, Cre in urine and RhoA protein in kidney tissue in the high-dose group were significantly decreased (P<0.05), the levels of Alb, Cre, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue of the low-dose group, and the levels of RhoA, ROCK1 and ROCK2 mRNA expressions in kidney tissue of the middle-dose group were significantly increased (P<0.05). Compared with the low-dose group, the levels of Alb, A/C in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the middle and high-dose groups, Cre in urine of the high-dose group were significantly decreased (P<0.05). Compared with the middle-dose group, the levels of Alb, Cre in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions, ROCK2 mRNA expression in kidney tissue in the high-dose group were significantly decreased (P<0.05). Conclusion:Icariin may protect glomerular endothelium and podocyte by affecting RhoA/ROCK pathway in the treatment of NS rats.