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。
Objective To explore whether astragalosideⅣ(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-Ⅳ20 mg/kg group and IR+AS-Ⅳ40 mg/kg group.One month after intraperitoneal injection of AS-Ⅳ,the mice were irradiated with8 Gy 60 Coγand 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 factorα(TNF-α)]increased significantly(P<0.01);AS-Ⅳpretreatment 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-Ⅳmay 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.
作者
徐郁琴
丁艳平
刘淑宁
康洁
邵宝平
XU Yu-qin;DING Yan-ping;LIU Shu-ning;KANG Jie;SHAO Bao-ping(School of Life Science,Northwest Normal University,Lanzhou 730070,China;School of Life Science,Lanzhou University,Lanzhou 730000,China)
出处
《解剖学报》
CAS
CSCD
北大核心
2021年第4期621-627,共7页
Acta Anatomica Sinica
基金
国家自然科学基金(31760271)。
关键词
黄芪甲苷
肾损伤
辐射
TOLL样受体4
核因子ΚB
免疫炎症反应
免疫组织化学
小鼠
AstragalosideⅣ
Kidney injury
Radiation
Toll-like receptor 4
Nuclear factor kappa B
Immunoinflammatory response
Immunohistochemistry
Mouse
