【摘要】 目的探讨黄芪甲苷(AS-Ⅳ)是否通过toll样受体4(TLR4)/核因子κB(NF-κB)介导的信号通路对辐射诱导肾脏损伤起到保护作用。方法将小鼠分为正常对照组、DMSO溶剂组、辐射组(IR)、IR+AS-Ⅳ20 mg/kg组和IR+AS-Ⅳ40 mg/kg组。小鼠给予AS-Ⅳ腹腔注射1个月后,以8Gy的60Coγ进行全身辐射。测定血清肌酐(Cr)和尿酸(BUA)的含量,进行肾组织HE和免疫组织化学染色,并检测肾脏TLR4/NF-κB信号通路相关蛋白的表达情况。结果与对照组相比,辐射组小鼠血清中Cr和BUA含量明显升高(P<0.001),肾小球萎缩,肾小管扩张,TLR4和髓样分化因子88(MyD88)阳性表达明显增多(P<0.001),且TLR4/NF-κB信号通路相关蛋白[TLR4、MyD88、NF-κB、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)]表达极显著升高(P<0.01); AS-Ⅳ预处理能降低血清中Cr和BUA的含量(P<0.05,P<0.01或P<0.001),明显改善辐射所致的病理反应,降低TLR4/NF-κB信号通路相关蛋白的表达(P<0.05或P<0.01)。结论 AS-Ⅳ可能通过TLR4/NF-κB信号通路下调炎症因子的释放,从而改善辐射诱导的小鼠肾损伤,发挥保护作用。更多还原

【Abstract】 Objective To explore whether astragaloside Ⅳ( AS-Ⅳ) can protect radiation-induced kidney injury through toll-like receptor 4( TLR4)/nuclear factor kappa B( NF-κB)-mediated signaling pathway. Methods The mice were randomly divided into normal control group,DMSO solvent group,irradiation group( IR),IR + AS-Ⅳ 20 mg/kg group and IR + AS-Ⅳ 40 mg/kg group. One month after intraperitoneal injection of AS-Ⅳ,the mice were irradiated with8 Gy 60 Coγ and to the content of serum creatinine( Cr) and uric acid( BUA) in serum were determined,HE and immunohistochemical staining,and expression of TLR4/NF-κB signaling pathway related protein in kidney were performed.Results Compared with the control group,the levels of Cr and BUA in the serum of the radiation group increased significantly( P<0. 001),glomerular atrophy and tubular expansion,TLR4 and myeloid differentiation factor 88( MyD88)positive expression increased significantly( P < 0. 001),and the expression of TLR4/NF-κB signaling pathway-related proteins[TLR4,MyD88,NF-κB,interleukin-1β( IL-1β),tumor necrosis factor α( TNF-α) ]increased significantly( P<0. 01); AS-Ⅳ pretreatment can reduce the content of Cr and BUA in serum( P<0. 05,P<0. 01 or P<0. 001),significantly improve the pathological response caused by radiation,and reduce the expression of TLR4/NF-κB signaling pathway-related proteins( P< 0. 05 or P < 0. 01). Conclusion AS-Ⅳ may down-regulate the release of inflammatory factors through the TLR4/NF-κB signaling pathway,thereby improving radiation-induced kidney injury in mice and playing a protective role.更多还原