沙利度胺减轻肾病综合征小鼠肾脏纤维化

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (9): 1291-1296.

沙利度胺减轻肾病综合征小鼠肾脏纤维化

高宏宇¹, 张国英¹, 刘秋菊^2*, 王晔¹, 张莉¹, 陈超¹

1.保定市第二医院肾病科,河北保定 071051;
2.河北大学附属医院肾内科,河北保定 071000

收稿日期:2020-07-06 修回日期:2021-01-09 出版日期:2021-09-05 发布日期:2021-09-02
通讯作者: *1789025031@qq.com
基金资助:
保定市科技计划(18ZF013)

Thalidomide alleviates renal fibrosis of nephrotic syndrome mice

GAO Hong-yu¹, ZHANG Guo-ying¹, LIU Qiu-ju^2*, WANG Ye¹, ZHANG Li¹, CHEN Chao¹

1. Department of Nephrology, the Second Hospital of Baoding, Baoding 071051;
2. Department of Nephrology, the Affiliated Hospital, Hebei University, Baoding 071000, China

Received:2020-07-06 Revised:2021-01-09 Online:2021-09-05 Published:2021-09-02
Contact: *1789025031@qq.com

摘要/Abstract

摘要： 目的探讨沙利度胺对肾病综合征小鼠表皮生长因子受体(EGFR)/细胞外信号调节激酶(ERK)信号通路及肾脏纤维化的影响。方法将小鼠随机分为对照组、模型组(制备膜性肾病模型)、沙利度胺组(灌胃给予沙利度胺溶液100 mg/kg)、来氟米特组(灌胃给予来氟米特溶液5 mg/kg),每组15只。1天1次,连续给药4周。分别在造模前、造模后、治疗4周后检测小鼠24 h尿蛋白定量(24 h-Upro);治疗4周后,全自动生化分析仪检测小鼠生化指标;酶联免疫吸附(ELISA)检测血清中炎性因子白介素-6(IL-6)、白介素-8(IL-8)、肿瘤坏死因子α(TNF-α)表达;苏木精-伊红(HE)染色、马松(Masson)染色、高碘酸-无色品红(PAS)染色观察肾组织病理变化;RT-qPCR和Western blot检测肾脏组织中EGFR、ERK mRNA及蛋白表达。结果与对照组相比,模型组小鼠肾小球体积增大,肾小管中有空泡性病变,肾小管上皮细胞有嗜复红蛋白沉积,小鼠24 h-Upro、血清中TC、TG、BUN、Scr含量、血清中炎性因子IL-6、IL-8、TNF-α含量、肾脏组织中EGFR、ERK mRNA水平及p-EGFR/EGFR、p-ERK/ERK蛋白表达显著升高(P＜0.05);与模型组相比,来氟米特组、沙利度胺组小鼠上述病理症状明显减轻,小鼠24 h-Upro、血清中TC、TG、BUN和Scr含量、血清中炎性因子IL-6、IL-8、TNF-α表达、肾脏组织中EGFR、ERK mRNA水平及p-EGFR/EGFR、p-ERK/ERK蛋白表达显著回降(P＜0.05)。结论沙利度胺可能通过抑制EGFR/ERK信号通路减轻肾脏损伤,抑制肾脏纤维化。

关键词: 沙利度胺, 肾病综合征, 表皮生长因子受体/细胞外信号调节激酶信号通路

Abstract: Objective To investigate the effects of thalidomide on epidermal growth factor receptor (EGFR)/extracellular signal regulated kinase (ERK) signaling pathway and renal fibrosis of nephrotic syndrome mice. Methods The mice were randomly divided into control group and model group with 15 in each to prepare membranous nephropathy model, thalidomide group was given thalidomide solution 100 mg/kg, leflunomide group was given leflunomide solution 5 mg/kg per day for four weeks. The 24-hour urine protein (24 h-Upro) was measured before, after and 4 weeks after treatment; after 4 weeks of treatment, the biochemical indexes of mice in each group were detected by automatic biochemical analyzer; the levels of serum interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) were detected by ELISA.HE staining, Masson staining and periodic acid Schiff (PAS) staining were used to observe the renal pathological changes in each group; the expression of EGFR,ERK mRNAs and proteins were detected by RT-qPCR and Western blot. Results Compared with the control group, the 24 h-Upro in the model group was significantly increased (P＜0.05). After 4 weeks of treatment,the glomerulus volume of the model group was larger, there were vacuolar lesions in the renal tubules, and the epithelial cells of the renal tubules had the deposition of eosinophilic protein, and the 24h-Upro, the contents of TC, TG, BUN and Scr in serum, the expression of IL-6, IL-8 and TNF-α in serum, the mRNA level of EGFR and ERK in renal tissue and the protein expression of p-EGFR/EGFR and p-ERK/ERK were all significantly higher(P＜0.05). As compared with those in the model group, the above pathological symptoms in leflunomide group and thalidomide group were significantly reduced, and the 24 h-Upro, the contents of TC, TG, BUN and Scr in serum, the expressions of IL-6, IL-8 and TNF-α in serum, the mRNA level of EGFR and ERK in renal tissue, the protein expressions of p-EGFR/EGFR and p-ERK/ERK were all significantly lower (P＜0.05). Conclusions Thalidomide may alleviate renal damage and inhibit renal fibrosis by inhibiting EGFR/ERK signaling pathway.

Key words: thalidomide, nephrotic syndrome, epidermal growth factor receptor/extracellular signal regulated kinase signal pathway

中图分类号:

R915

高宏宇, 张国英, 刘秋菊, 王晔, 张莉, 陈超. 沙利度胺减轻肾病综合征小鼠肾脏纤维化[J]. 基础医学与临床, 2021, 41(9): 1291-1296.

GAO Hong-yu, ZHANG Guo-ying, LIU Qiu-ju, WANG Ye, ZHANG Li, CHEN Chao. Thalidomide alleviates renal fibrosis of nephrotic syndrome mice[J]. Basic & Clinical Medicine, 2021, 41(9): 1291-1296.

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