肾安汤对顺铂诱导的肾损伤大鼠TLR4/NF-κB信号通路的调节及肾组织修复作用研究  

Research on the regulation of TLR4/NF-κB pathway and reparaive effect of Shen’an Decoction on cisplatin-induced kidney injuried rat

作　　者：陈志成[1] 黄玉涓 周柯 胡剑卓[1] Chen Zhicheng;Huang Yujuan;Zhou Ke;Hu Jianzhuo(Department of Nephrology and Endocrinology,the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410005,China;Department of Neurology,the Fourth Hospital of Changsha,Changsha 410006,China)

机构地区：[1]湖南中医药大学第二附属医院肾病内分泌科,长沙410005 [2]长沙市第四医院神经内科,410006

出　　处：《国际中医中药杂志》2021年第11期1097-1102,共6页International Journal of Traditional Chinese Medicine

基　　金：湖南省卫生健康委科研计划课题项目(20201213)。

摘　　要：目的:研究肾安汤通过调节TLR4/NF-κB信号通路对顺铂诱导的大鼠肾损伤的保护作用,探讨其作用机制。方法:将60只SD大鼠按体重分为空白组、模型组、阳性对照组、肾安汤高剂量组、肾安汤中剂量组、肾安汤低剂量组,每组10只。除空白组外,其余各组采用腹腔注射顺铂7.5 mg/kg制备急性肾损伤大鼠模型。造模后,肾安汤高、中、低剂量组分别灌胃肾安汤水煎液0.698、1.395、2.790 g/ml,阳性对照组灌胃盐酸贝那普利混悬液5 mg/kg,1次/d,连续灌胃14 d。采用HE染色观察各组大鼠肾组织病理学改变,采用ELISA法检测各组大鼠血清BUN、肌酐(Cr)、胱抑素C(Cys-c)及TNF-α、IL-6水平,Western-blot法检测肾组织TLR-4、NF-κB p65、髓样分化因子(MyD88)、肿瘤坏死因子受体相关因子6(TRAF-6)蛋白表达。结果:与模型组比较,肾安汤低、中、高剂量组大鼠一般生长情况明显改善,肾脏系数降低(P<0.05);肾安汤低、中、高剂量组大鼠血清BUN、Cr、Cys-c、TNF-α、IL-6水平降低(P<0.05),肾组织中TLR-4[(0.54±0.07)、(0.52±0.09)、(0.41±0.04)比(0.86±0.06)]、NF-κB p65[(0.74±0.02)、(0.72±0.06)、(0.67±0.05)比(0.93±0.03)]、MyD88[(0.86±0.02)、(0.82±0.03)、(0.61±0.02)比(1.04±0.03)]、TRAF-6[(0.65±0.04)、(0.58±0.08)、(0.54±0.07)比(0.90±0.06)]蛋白表达下调(P<0.05),且具有一定的浓度依赖性。结论:肾安汤可通过抑制TLR4/NF-κB信号通路,减轻顺铂诱导的大鼠肾损伤病理改变,从而保护大鼠肾功能。Objective:To explore the protective effect of Shen’an decoction on cisplatin induced renal injury in rats by regulating TLR4/NF-κB signaling pathway.Methods:Sixty SD rats were randomly divided into blank group,model group,positive control group,high dose Shen’an Decoction group,medium dose Shen’an Decoction group and low dose Shen’an Decoction group,with 10 rats in each group.Except the blank group,the other groups were intraperitoneally injected with cisplatin 7.5 mg/kg to prepare the acute kidney injured rat model.After the modeling,the high,medium and low dose groups of Shen’an Decoction were gavaged with 0.698,1.395 and 2.790 g/ml Shen’an Decoction respectively,and the positive control group was gavaged with benazepril hydrochloride suspension of 5 mg/kg,once a day for 14 days.The kidney histopathological changes of rats in each group were observed by HE staining.The content of BUN,creatinine(CR),Cystatin C(Cys-C),TNF-α,and IL-6 in serum were detected by ELISA.The expression of TLR-4,NF-κB p65,myeloid differentiation factor(MyD88),and tumor necrosis factor receptor related factor 6(TRAF-6)in renal tissue were detected by Western blot.Results:Compared with the model group,the growth condition of rats in each dose group of Shen’an Decoction was significantly improved(P<0.05),and the kidney coefficient was significantly decreased(P<0.05).The serum levels of BUN,Cr,Cys-C,TNF-α,IL-6 of rats in each dose group of Shen’an Decoction were significantly decreased(P<0.05).The expression of TLR-4(0.54±0.07,0.52±0.09,0.41±0.04 vs.0.86±0.06),NF-κB(0.74±0.02,0.72±0.06,0.67±0.05 vs.0.93±0.03),MyD88(0.86±0.02,0.82±0.03,0.61±0.02 vs.1.04±0.03),and TRAF-6(0.65±0.04,0.58±0.08,0.54±0.07 vs.0.90±0.06)in kidney tissue of rats in each dose group of Shen’an Decoction was significantly decreased(P<0.05).Conclusion:Shen’an Decoction can protect the renal function of rats by inhibiting TLR4/NF-κB signaling pathway and alleviating the pathological changes of renal injury induced by cisplatin.

关 键 词：急性肾损伤 肾安汤 TLR4/NF-κB通路 炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]