Efficacy research of immune inhibitors sequential therapy according to the cell cycle for the adriamYcin-induced nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To assess the efficacy of different sequential therapy regimens according to the theory of cell cycle on adriamycin-induced nephropathy (AIN) rats. Methods SD rats were randomly divided into five groupscontrol group (n=8),AIN model group (n=8),MP+ CsA+MMF group (n=8),MP+CsA+CTX treated group (n=8) and MP+FK506+Rapa group (n=8).The levels of 24-hour urinary protein,serum total protein (TP),albumin (Alb),cholesterin (Chol),triglyeride (TG),serum urea nitrogen (BUN),serum creatinine (Scr) were measured.The renal pathological changes were observed by light microscope.The expressions of nephrin and podocin were analyzed by immunohistochemistry and real-time PCR.The expression of CTGF was detected by Western blotting. Results (1)Compared with control group,the levels of 24-hour urinary protein in AIN model group were obviously increased at 2nd,4th,8th and 12th week (all P＜0.01).The level of 24-hour urinary protein were obviously decreased in treatment groups at 8th and 12th week than those in AIN model group (all P＜0.05). (2)The levels of TP and Alb were significantly lower in AIN model group than those in control group (all P＜0.01),and the levels of TG and Chol were significantly higher in AIN model group than that in control group (all P＜0.01).The levels of TP and Alb were significantly higher and the levels of TG and Chol were significantly lower in treatment groups than those in AIN model group (all P ＜0.05). (3)The results of immunohistochemistry indicated the expressions of nephrin and podocin in treatment group rats were obviously higher than those in AIN model group (all P＜0.01). (4)The results of Western blotting indicated the expression of CTGF in treatment group rats was higher than that in AIN model group (P＜0.05).The effect of inhibitting fibrous degeneration in MP +FK506 +Rapa group was more greater than other treatment groups. Conclusions Sequential combined regimens according to the cell cycle can improve the pathological change in adriamycin-induced nephropathy rats,reduce the urine protein,increase the levels of TP and Alb,decrease the levels of TG and Chol,increase the expression of nephrin and podocin,and ameliorate kidney fibrosis.