黄芪对急性肾损伤向慢性肾脏病转化小鼠Klotho/NF-κB信号通路的影响  

Effect of astragalus membranaceus on Klotho/NF-κB signaling pathway in mice model of acute kidney injury to chronic kidney disease transition

作　　者：张冬[1] 李宗英 高原[1] 肖娜[1] ZHANG Dong*;LI Zong-ying;GAO Yuan;XIAO Na(Department of Nephrology,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院肾内一科,河北沧州061000

出　　处：《解剖科学进展》2024年第4期397-400,共4页Progress of Anatomical Sciences

基　　金：沧州市重点研发计划指导项目(213106065)。

摘　　要：目的探究黄芪对缺血再灌注(IRI)所致急性肾损伤(AKI)向慢性肾脏病转化(CKD)小鼠肾功能的影响及可能机制。方法50只4周龄C57BL/6小鼠随机分为假手术组(Sham组)、模型组(IRI组)和黄芪低、中、高剂量组(L-A+IRI,M-A+IRI,H-A+IRI组),建模后28d,测定小鼠体重、血清尿素氮(BUN)、肌酐(SCR)、24 h尿蛋白及炎症因子[白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)]水平,HE染色观察肾组织病理变化,RT-PCR及Western blot检测Klotho、核因子κB p65(NF-κB p65)mRNA及蛋白表达。结果黄芪呈剂量依赖性降低小鼠24 h尿蛋白、血清BUN、SCr、IL-6、TNF-α、IL-1β水平、肾组织NF-κB p65、p-IκBαmRNA及蛋白表达,缓解肾小球及肾小管炎性细胞浸润和损伤,促进小鼠体质量、Klotho mRNA及蛋白表达增加(P<0.05)。结论黄芪能通过上调Klotho表达来抑制NF-κB信号通路,减轻AKI向CKD转化小鼠肾脏炎症浸润和病理损伤。Objective To explore the effects and mechanisms of astragalus membranaceus on renal function in mice with acute kidney injury(AKI)to chronic kidney disease(CKD)transition due to ischemia-reperfusion injury(IRI). Methods Fifty 4-week-old C57BL/6 mice were randomly assigned into sham-operated group(Sham group), model group(IRI group), and low-, medium-, and high-Astragalus dosage groups(L-A+IRI, M-A+IRI, and H-A+IRI groups). After 28 days of model construction, body weight, blood urea nitrogen(BUN), serum creatinine(SCR), 24h urinary protein and inflammatory cytokines[interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)]levels were measured in mice, and renal histopathological changes were observed by hematoxylin-eosin(HE)staining. The mRNA and protein expression of Klotho and nuclear factor κB p65(NF-κB p65)were detected by RT-PCR and Western blot. Results Astragalus membranaceus decreased the levels of urinary protein, BUN, SCr, IL-6, TNF-α, IL-1β in serum of mice, decreased the expressions of NF-κB p65, p-IκBα mRNA and protein in renal tissue in a dose-dependent manner, and alleviated the infiltration and injury of glomerular and renal tubule inflammatory cells, increased body weight, expression of Klotho mRNA and protein in mice(P<0.05). Conclusion Astragalus membranaceus can inhibit the NF-κB signalling pathway by up-regulating Klotho expression and attenuating renal inflammatory infiltration and pathological injury in AKI to CKD transition mice.

关 键 词：急性肾损伤 慢性肾脏病 黄芪 缺血再灌注 

分 类 号：R692[医药卫生—泌尿科学]