摘要
目的探讨STAT3抑制剂S3I-201对小鼠实验性肾小管间质纤维化的保护作用。方法采用单侧输尿管梗阻手术的方法建立肾小管间质纤维化模型。将实验小鼠随机分为药物假手术组(Sham+S3I-201),安慰剂假手术组(Sham+Vehicle),药物造模组(UUO+S3I-201),安慰剂造模组(UUO+Vehicle)4组,通过腹腔注射S3I-201溶液(药物)或0.05%DMSO PBS(安慰剂)给药,每天给药一次。造模第7天时留取肾脏标本,用Masson染色和颜色面积测算法评估胶原蛋白沉积的情况。用qRT-PCR法检测肾组织内趋化因子配体16(CXCL16),白介素-1β(IL-1β),细胞间黏附分子1(ICAM-1),转化生长因子-β(TGF-β),肿瘤坏死因子(TNF-α)的mRNA表达,用免疫组化法染色和免疫印迹法检测PDGFRβ蛋白在梗阻肾脏内的表达。结果 UUO+Vehicle小鼠的肾间质胶原蛋白沉积显著高于Sham+Vehicle组(P<0.05)。UUO+Vehicle小鼠肾组织CXCL16,IL-1β,ICAM-1,TGF-β,TNF-α的mRNA表达显著高于Sham+Vehicle组(P<0.05),UUO+Vehicle小鼠肾组织血小板来源生长因子受体β(PDGFRβ)蛋白表达显著高于Sham+Vehicle组(P<0.05)。经过S3I-201治疗7 d后,UUO+S3I-201小鼠的上述各项指标均显著低于UUO+Vehicle(P<0.05)。结论 S3I-201通过抑制多种细胞因子的mRNA表达,以及降低PDGFRβ蛋白的表达,减轻实验性肾小管间质纤维化小鼠的肾间质炎症反应,从而发挥肾脏保护作用。
Objective To investigate the protective effects of STAT3 inhibitor S3I-201 in experimental renal tubulointerstitial fibrosis of mice.Methods A model of renal tubulointerstitial fibrosis was established by the method of unilateral ureteral obstruction (UUO).The experimental mice were randomly divided into a drug-sham operation group (Sham+S3I-201),a placebo-sham operation group (Sham+Vehicle),a drug-model group (UUO+S3I-201),and a placebo-model group (UUO+Vehicle).The four groups were administered intraperitoneally with S3I-201 solution (drug) or 0.05% DMSO PBS (placebo),once daily.Kidney specimens were taken on the 7th day of modeling,and collagen deposition was assessed by Masson staining and color area measurement algorithm.The qRT-PCR method was used to detect the mRNA expression of chemokine C-X-C-motif ligand 16 (CXCL16),interleukin-1β(IL-1β),intercellular adhesion molecule-1 (ICAM-1),transforming growth factor-β(TGF-β),and tumor necrosis factor-α(TNF-α),while immunohistochemical staining and immunoblotting methods were used to detect the protein expression of platelet-derived growth factor receptor β(PDGFRβ) in the obstructed kidneys.Results Renal interstitial collagen deposition was significantly higher in the placebo-model group (UUO+ Vehicle) than in the placebo-sham operation group (Sham+Vehicle)(P<0.05).The mRNA expression of CXCL16,IL-1β,ICAM-1,TGF-β,and TNF-α were also significantly higher in the placebo-model group (UUO+Vehicle) than in the placebo-sham operation group (Sham+Vehicle)(P<0.05).The protein expression of PDGFRβ was significantly higher in the placebo-model group (UUO+Vehicle) than in the placebo-sham operation group (Sham+Vehicle)(P<0.05).After S3I-201 treatment for 7 days,the above indexes were significantly lower in the drug-model group (UUO+S3I-201) than in placebo-model group (UUO+ Vehicle).Conclusion S3I-201 had a renal protective effect by inhibiting mRNA expression of various cytokines,decreasing protein expression of PDGFRβ,and reducing renal interstitial inflammati
作者
梅艳
朱凤阁
朱晗玉
段姝伟
洪权
马倩
蔡广研
陈香美
Mei Yan;Zhu Fengge;Zhu Hanyu;Duan Shuwei;Hong Quan;Ma Qian;Cai Guangyan;Chen Xiangmei(Department of Nephrology,Chinese PLA General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing 100853,China)
出处
《中华肾病研究电子杂志》
2018年第4期167-171,共5页
Chinese Journal of Kidney Disease Investigation（Electronic Edition）
基金
国家自然科学基金(81330019
81500566)
