肾衰Ⅱ号方对慢性肾功能衰竭大鼠肾组织NF-κB/TNF-α信号通路表达的影响

Effects of Shenshuai Ⅱ Decoction on NF-κB/TNF-α Signaling Pathway Expressions in Renal Tissues of Chronic Renal Failure Rats

目的观察肾衰Ⅱ号方对慢性肾功能衰竭大鼠肾组织NF-κB/TNF-α信号通路表达的影响,探讨其改善慢性肾功能衰竭微炎症状态、延缓慢性肾脏病进展的作用机制。方法采用5/6(ablation/infarction,A/I)肾切除法制作慢性肾功能衰竭动物模型。实验大鼠随机分为模型组、西药对照组、肾衰Ⅱ号方组,每组14只,另设假手术组14只,各给药组给予相应药物。测定大鼠血肌酐(SCr)、尿素氮(BUN)、内生肌酐清除率(CCr),采用Western blot测定磷酸化核因子-κB(p-NF-κB)p65、NF-κB p65、肿瘤坏死因子-α(TNF-α)蛋白表达,RT-PCR测定TNF-αm RNA表达。结果与假手术组比较,模型组SCr、BUN水平明显升高,CCr明显降低(P<0.01),左肾质量/体质量明显增加(P<0.05),肾脏皮质、髓质p-NF-κB p65、NF-κB p65及TNF-α表达均明显升高(P<0.01);与模型组比较,肾衰Ⅱ号方组、西药对照组SCr、BUN水平明显降低(P<0.05,P<0.01),CCr明显升高(P<0.01),左肾质量/体质量明显降低(P<0.05),肾衰Ⅱ号方组在改善肾功能方面优于西药对照组(P<0.05);肾衰Ⅱ号方组、西药对照组肾脏皮质、髓质p-NF-κB p65、NF-κB p65及TNF-α表达均明显降低(P<0.01),肾衰Ⅱ号方组下调NF-κB/TNF-α信号通路表达作用优于西药对照组(P<0.01)。结论肾衰Ⅱ号方可能通过下调NF-κB/TNF-α信号通路的表达,改善慢性肾功能衰竭微炎症状态,减轻肾间质纤维化,达到延缓肾功能减退的作用。

Objective To observe the effects of ShenshuaiⅡDecoction on NF-κB/TNF-αpathway expressions in the renal tissues of chronic renal failure rats;To explore the mechanism of improving chronic inflammation of chronic renal failure and delaying the progression of chronic kidney disease.Methods Rats,which were made into chronic renal failure animal models by means of 5/6 ablation/infarction,were divided randomly into model group,Western medicine control group,and ShenshuaiⅡDecoction group,with 14 rats in each group.Meanwhile,sham-operation group was set up with 14 rats.Each administration group was given relevant medicine for intervention.SCr,BUN,and CCr were tested.Western blot was used to detect the expression of p-NF-κB p65,NF-κB p65 and TNF-αprotein.RT-PCR was used to determine the expression of TNF-αmRNA.Results Compared with the sham-operation group,the levels of SCr and BUN in the model group increased significantly,while CCr decreased significantly(P<0.01),and the left kidney mass/body mass significantly increased(P<0.05).The p-NF-κB p65,NF-κB p65 and TNF-αin renal cortex and medulla increased significantly(P<0.01).Compared with the model group,the levels of SCr and BUN in the ShenshuaiⅡDecoction group and the Western medicine control group were significantly lower(P<0.05,P<0.01),while CCr was significantly higher(P<0.01),and the left kidney mass/body mass was significantly reduced(P<0.05).ShenshuaiⅡDecoction group was superior to Western medicine control group in improving renal function(P<0.05).The expressions of p-NF-κB p65,NF-κB p65 and TNF-αin renal cortex and medulla of ShenshuaiⅡDecoction group and Western medicine control group were significantly decreased(P<0.01).The expression of NF-κB/TNF-αsignaling pathway in ShenshuaiⅡDecoction group was superior to that of Western medicine control group(P<0.01).Conclusion ShenshuaiⅡDecoction can improve the micro-inflammatory state of chronic renal failure,reduce renal interstitial fibrosis,and delay the effect of renal dysfunction by down-regulating the expression of NF-κB/TNF-αsignal pathway expressions.