中介素改善IgA肾病大鼠肾脏结构和功能以及微血管损伤  

Intermedin improves renal structure and function and microvascular injury in IgA nephropathy rats

作　　者：王宗隅 范琦强 赵艳[1,2,3] 王艳红 罗琰琨[1,2,3] 周芸[1,2,3] WANG Zong-yu;FAN Qi-qiang;ZHAO Yan;WANG Yan-hong;LUO Yan-kun;ZHOU Yun(Dept of Nephrology,the Fifth Clinical Medical College of Shanxi Medical University(Shanxi Provincial People′s Hospital),Taiyuan 030012,China;Key Laboratory of Renal Disease of Shanxi Province,Taiyuan 030012,China;Experimental Animal Genetic Engineering Research Center of Shanxi Province,Taiyuan 030012,China;Dept of Microbiology and Immunology of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第五临床医学院(山西省人民医院)肾内科,山西太原030012 [2]肾脏病山西省重点实验室,山西太原030012 [3]山西省实验动物基因工程研究中心,山西太原030012 [4]山西医科大学微生物与免疫教研室,山西太原030001

出　　处：《中国药理学通报》2022年第10期1559-1564,共6页Chinese Pharmacological Bulletin

基　　金：山西省重点研发计划项目(No 201803D31163);山西省卫计委科研项目(No 201713);山西省研究生教育创新项目(No 2020SY279);山西省“136”兴医工程领军临床专科科研项目(No xy2018003)。

摘　　要：目的探讨血管活性物质中介素(intermedin,IMD)对IgA肾病大鼠肾脏结构和功能以及微血管损伤的影响。方法构建IgA肾病大鼠,分为正常对照组(Control组)、IgA肾病组(IgAN组)、正常对照+IMD组(Control+IMD组)、IgA肾病+IMD组(IgAN+IMD组)。全自动分析仪检测尿蛋白、Scr、BUN水平;HE和PAS染色分别观察大鼠肾脏病理的改变;免疫荧光观察大鼠肾小球IgA的沉积;RT-PCR法检测TGF-β1、α-SMA、BMP-7、E-cadherin、TSP-1及VEGF的mRNA表达水平,Western blot法检测其蛋白表达水平。结果与IgAN组相比,IMD干预治疗后大鼠尿蛋白及Scr水平降低,肾脏病理的损伤减轻,肾小球IgA沉积减少;同时,IMD下调TGF-β1、α-SMA及TSP-1等血管损伤因子的表达,上调BMP-7、E-cadherin及VEGF等血管保护因子。结论中介素能够延缓IgA肾病的进展,可能与其减少IgA在肾小球系膜区沉积,并调节血管损伤与修复相关细胞因子的表达来维持血管的功能有关。Aim To investigate the effects of intermedin on renal structure and function and microvascular injury in IgA nephropathy rats.Methods An IgA nephropathy rat model was constructed and divided into control group,IgA nephropathy group,control treated with IMD group and IgA nephropathy treated with IMD group.The urine protein,Scr and BUN were detected by automatic analyzer.The pathological changes of kidney were observed by HE and PAS staining.IgA deposition was observed by immunohistochemistry.The mRNA expressions of TGF-β1,α-SMA,BMP-7,E-cadherin,TSP-1 and VEGF were detected by RT-PCR,and the protein expressions of TGF-β1,α-SMA,BMP-7,E-cadherin,TSP-1 and VEGF were detected by Western blot.Results Compared with IgAN group,the levels of Scr and urine protein decreased after IMD intervention,kidney pathological injury was alleviated,and IgA deposition was reduced.Meanwhile,IMD down-regulated the expression of TGF-β1,α-SMA and TSP-1,and up-regulated the expression of BMP-7,E-cadherin and VEGF.Conclusions Intermedin can slow down the progression of IgA nephropathy,which may be related to reducing IgA deposition in the mesangial region,down-regulating the expression of vascular injury factors,and regulating the expression of vascular injury and repair related cytokines to maintain vascular function.

关 键 词：中介素 血管活性物质 IGA肾病 大鼠 微血管损伤 肾功能 

分 类 号：R-332[医药卫生] R322.13R322.61R692.31R977.1