肾衰饮对CRF大鼠TLR4/MyD88/NF-κB信号通路及炎症状态的影响

Effect of shenshuaiyin on TLR4/MyD88/NF-κB signal pathway and inflammatory state in CRF rats

目的基于toll样受体(TLR)4/髓样细胞分化因子(MyD)88/核转录因子(NF)-κB信号通路探讨肾衰饮对慢性肾衰竭(CRF)大鼠炎症状态的干预机制。方法将60只SD大鼠,随机分成四组,分别为正常组、模型组、尿毒清组和肾衰饮组。进行4 w的干预治疗后,苏木素-伊红(HE)染色观察大鼠肾脏组织病理形态改变,检测血肌酐(Scr)、尿素氮(BUN),酶联免疫吸附试验(ELISA)检测大鼠血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α水平,分别采用免疫组化法和Western印迹检测大鼠肾脏组织TLR4、MyD88、NF-κB蛋白表达。结果与正常组比较,模型组HE染色显示大鼠肾脏组织发生明显病理改变,血Scr、BUN、IL-1β、IL-6、TNF-α水平均显著升高(P<0.01),肾脏组织中TLR4、MyD88、NF-κB蛋白表达均显著升高(P<0.01);与模型组比较,尿毒清组和肾衰饮组肾脏组织病理改变明显改善,血清Scr、BUN、IL-1β、IL-6、TNF-α水平均显著降低(P<0.01),肾脏组织中TLR4、MyD88、NF-κB蛋白表达均显著降低(P<0.01)。结论肾衰饮能有效改善CRF大鼠的肾功能,其机制可能是抑制TLR4/MyD88/NF-κB信号通路从而抑制炎症反应发生,达到治疗CRF的目的。

Objective Based on the toll like receptor(TLR)4/myeloid differentiation factor(MyD)88/nuclear factor(NF)κB signaling pathway,the mechanism of shenshuaiyin on the inflammatory state of chronic renal failure(CRF)rats was explored.Methods 60 SD rats were randomly divided into normal,model,Niaoduqing and shenshuaiyin groups.After 4 weeks of intervention treatment,HE staining was used to observe the renal histopathology,the levels of serum creatinine(Scr)and urea nitrogen(BUN),the levels of serum interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-αwere detected by ELISA and the levels of kidney tissue TLR4,MyD88 and NF-κB were detected by immunohistochemistry and Western blot.Results Compared with normal group,the renal tissue of rats had obvious pathological changes,the serum levels of Scr,BUN,IL-1β,IL-6,TNF-αwere significantly increased,and TLR4,MyD88,NF-κB protein in renal tissue were all increased in the model group(all P<0.01).Compared with model group,the pathological changes of renal tissue were significantly improved,and the serum levels of Scr,BUN and NF-κB were significantly improved,the levels of IL-1β,IL-6 and TNF-αwere all decreased,and TLR4,MyD88 and NF-κB protein in kidney were all decreased in the group of Niaoduqing and shenshuaiyin(all P<0.01).Conclusions Shenshuaiyin could effectively improve renal function in CRF rats,and its mechanism might be related to inhibiting TLR4/MyD88/NF-κB signal pathway to inhibit the occurrence of inflammatory reaction,so as to achieve the purpose of treating CRF.