黄芪甲苷调控p38 MAPK信号通路治疗小鼠肾小管间质纤维化的实验研究  

Experimental Study of Astragaloside IV Regulating p38 MAPK Signaling Pathway in the Treatment of Renal Tubulointerstitial Fibrosis

作　　者：周淑娟[1] 李伟[1] ZHOU Shu-juan;LI Wei(Department of Nephrology,Yanan people's Hospital Shaanxi Province,Yan'an 716000)

机构地区：[1]陕西省延安市人民医院肾内科,陕西延安716000

出　　处：《医学临床研究》2021年第10期1547-1549,共3页Journal of Clinical Research

摘　　要：【目的】探讨黄芪甲苷(AS-N)调控p38丝裂原活化蛋白激酶(MAPK)通路对肾小管间质纤维化的改善作用。【方法】在C57BL/6小鼠中建立单侧输尿管结扎(UUO)致肾小管间质纤维化动物模型,分为假手术组(A组)、模型组(B组)和治疗组(C组)。C组连续7d予以20 mg/(kg·d)AS IV灌胃,A组和B组予以同等剂量的生理盐水灌胃。2周后取手术侧肾组织观察肾脏病理改变(Masson染色),实时定量PCR检测转化生长因子PB1(TGF-3I)mRNA表达。將NRK-49F细胞根据体外细胞培养基不同分为:阴性对照组、TGF-3l组(加TGF-p110 ng/mL刺激细胞)、TGF-31+AS-IN组(TGF-β1刺激前,分別添加制量50,100、200 ug/mL AS IV处理1h),观察NRK 49F细胞内p-p38蛋白水平(Western法)。【结果】A、B.C组肾组织TGF-31 mRNA相对表达分别为2.65±0.38.28.71±4.05和20.29±3.10,A组在较低水平;与A组相比,B、C组肾组织TGF-βI mRNA表达较A组明显增加(P<0.01),C组表达明显低于B组(P<0.05)。体外试验结果提示:p-p38蛋白水平,TGF-β1组>阴性对照组(P<0.01).TGF-Bl组>TGF-31+AS IV组(P<0.01),TGF B1+AS NV组中不同剂量各组比较差异均有显著性(P<0.01)。【结论】AS-IN可以下调TGF-β1表达水平,减轻肾小管间质纤维化,其保护作用可能与AS IV抑制p38 MAPK的磷酸化有关。【Objective】To investigate the effect of astragaloside Ⅳ(AS-Ⅳ)regulating p38 mitogen activated protein ki-nase(MAPK)pathway on renal tubulointerstitial fibrosis.【Methods】The animal model of tubulointerstitial fibrosis induced by unilateral ureteral ligation(UUO)was established in C57BL/6 mice and divided into sham operation group(group A),model group(group B)and treatment group(Group C).Group C was gavaged with 20 mg/(kg·d)as-iv for 7 days,and group A and B were gavaged with the same dose of physiological salt water.After 2 weeks,the pathological changes of the kidney were observed(Masson staining),and the transforming growth factor was detected by real-time quantitative TGF-β1 mRNA expression by PCR.According to different cell culture media,NRK-49F cells were divided into negative control group,TGF-β1 Group(with TGF-β110 ng/mL stimulated cells),TGF-β1+AS-IV group(before TGF-β1 stimulation,add doses of 50,100 and 200 pg/mL AS-W treatment for 1 h respectively),and the level of p-p38 protein in NRK-49F cells was observed(Western method).【Results】The relative expression of TGF-β1 mRNA in renal tissue of group A,B and C was 2.65±0.38,28.71±4.05 and 20.29+3.10,and the group A was at a lower level.Compared with the group A,the renal TGF-β1 mRNA expression in the group B and C was significantly higher than that in the group A(P<0.01),the expression in the group C was significantly lower than that in the group B(P<0.05).The results of in vitro test showed that p-p38 protein level,TGF-β1 GrouP〉negative control group(P<0.01),TGF-β1 GrooP>TGF-β1+AS-Ⅳ group(P<0.01),TGF-β1+AS-Ⅳ group 200 pg/mL<100 pg/mL<50 pg/mL(P<0.01).【Conclusion】AS-Ⅳ can reduce TGF-J31 level,reduce renal tubu-lointerstitial fibrosis,and its protective effect may be related to the inhibition of p38 MAPK phosphorylation by AS-IV.

关 键 词：肾疾病/病理学 小鼠 肾炎 间质性/病理学 黄芪甙 信号传导 

分 类 号：R693.2[医药卫生—泌尿科学]