Study Of Combined Treatment Of Traditional Chinese Medicine And Western Medicine In Adriamycin-induced Nephropathy Rats

Objective To study the effect of nuclear transcription factor-kappa B (NF-κB), tumor necrosis factor-α(TNF-α) and nitric oxide (NO) on minimal-changed nephrotic syndrome (MCNS). To investigate the possible mechanism of combined treatment with prednisone and shenkangling on MCNS. Methods SD rats were randomly divided into 13 groups. They were normal control group, adriamycin model control group, adriamycin groups treated with higl or low dose prednisone, adriamycin groups treated jointly with high dose predaisone and three dose shenkangling(low, mid and high dose respectively ), adriamycin groups treated jointly with low dose prednisone and three dose shenkangling(low, mid and high dose respectively ), adriamycin groups treated with three dose shenkangling(low, mid and high dose respectively ). Adriamycin groups were given addamycin (ADR) 5.5mg/kg through vena caudalis to duplicate the model of MCNS, at the same time, an equal volume of normal saline was given to the rats in normal control group by the same method. The activation of NF-κB in mononuclearcell were determined, the dynamic analysis of TNF-αand NO in the blood were evaluated. The relationship between the changing of NF-κB, TNF-α, NO and 24 hour urine protein excretion, serum albumin (ALB), total cholesterol (TC), triglyceride (TG), urea, creatinine (CRE)were studied, and the change of pathobiology in renal were observed. Results (1) Compared with normal control group, after injected ADR 14 days, the activation of NF-κB, the levels of TNF-αand NO were obviously increased(p＜0.01), the 24 hour urine protein excretion of rats in adriamycin groups were≥100mg/24h, TC and TG were obviously increased(p＜0.01), the level of ALB was decreased (p＜0.01), light pathological changes of nephridial tissue seen under light microscope and the fusion of foot process observed under electron microscope suggested that the model be successfully duplicated. (2) Compared with normal control group, the 24 hour urine protein excretion, the levels of TNF-α, NO, TC and TG of adriamycin model control group were increased gradually, and raise to maximum after injected ADR 35 days, but the ALB was gradually decreased (p＜0.01). General fusion of foot process observed under electron microscope.There were lots of red protein east in the nephric tubule. (3) After treated for three weeks, compared with adriamycin groups treated with high dose prednisone, the activation of NF-κB, the levels of TNF-α, NO, TC, TG and the 24 hour urine protein excretion of adriamycin groups treated jointly with high dose prednisone and high dose shenkangling, adriamyein groups treated jointly with high dose prednisone and mid dose shenkangling (p＜0.01). The level of ALB was markedly decreased (p＜0.01). The fusion of foot process recoverd mostly. (4) Compared with adriamycin groups treated with low dose prednisone after treated for three weeks, the values of above examinations of adriamycin groups treated jointly with low dose prednisone and high dose shenkangling were obviously improved (p＜0.01), while compared with adriamycin groups treated with high dose prednisone there was no significant difference (P＞0.05). (5) There was no synergistic effect when compared adriamycin groups treated with high dose prednisone with adriamycin groups treated jointly with high dose prednisone and low dose shenkangling (P＞0.05). Compared adriamycin groups treated with low dose prednisone with adriamycin groups treated jointly with low dose prednisone and low dose shenkangling, there was no synergistic effect (P＞0.05). Conclusions The abnormal activation of NF-κB might play significant role on the nosogenesis of MCNS. Kidney injury could be postpone and improved when treated jointly with prednisone and shenkangling, the effects of the two drugs were dose-dependent and time-dependent. It may contribute to the depression of activation of NF-κB, and the inhibition of production of TNF-αand NO.