环孢素引起肾小管上皮细胞培养液中肾损伤分子-1水平升高的机制

环孢素引起肾小管上皮细胞培养液中肾损伤分子-1水平升高
的机制
宋莲莲;赵军;于金宇;张文岚;薛丽娟;傅耀文
【期刊名称】《吉林大学学报（医学版）》
【年(卷),期】2014(000)006
【摘要】Objective To investigate the mechanism of increasing of the level of kidney injury molecule-1(KIM-1)in culture supernatant of human kidney cells(HKC)induced by cyclosporine A(CsA),and to clarify the relationships between the expression levels of KIM-1 and p38 MAPK pathway and
ERK1/2MAPK pathway in HKC. Methods The HKC at logarithmic growth phase were randomly divided into control group, CsA control group, CsA + p38 kinase inhibitor group, p38 kinase inhibitor group, CsA + ERK1/2 inhibitor group and ERK1/2 kinase inhibitor group.The inhibitory rates of proliferation of HKC in various groups were detected by MTT assay, and the expression levels of KIM-1 in HKC supernatant in various groups were detected by ELISA;the survival&nbsp;rates,apopototic rates and necrotic rates of the HKC in various groups were detected by flow cytometry. Results Compared with control group,the expression level of KIM-1 protein in the supernatant of HKC in CsA control group was significantly increased (P<0.05),and the survival rate was significantly decreased (P<0.05), while the apoptotic rate and the necrotic rate were significantly increased
(P<0.05 ). Compared with control group,the survival rates, the apoptotic
rates and the necrosis rates of cells in p38 kinase inhibitor group and
ERK1/2 kinase inhibitor group had no significant
differences(P>0.05).Compared with CsA control group,the expression levels of KIM-1 protein in CsA+ p38 kinase inhibitor group and CsA+
ERK1/2 kinase inhibitor group were significantly decreased (P<0.05),and
the survival rate was significantly increased (P<0.05),while the apoptotic rate and the necrotic rate were significantly decreased (P<0.05).Conclusion p38 MAPK pathway and ERK1/2MAPK pathway are involved in the process of up-regulation of the KIM-1 level in HKC culture supernatant induced by CsA,and the expression of KIM-1 may become the biochemical marker of clinical monitoring of CsA nephrotoxicity.%目的：探讨环孢素（CsA）引起人
肾小管上皮细胞（HKC）培养液中肾损伤分子-1（KIM-1）水平升高的作用机制，阐明KIM-1表达与 p38 MAPK通路和 EKR1/2 MAPK通路的关系。

方法：将处
于对数生长期的HKC分为空白组、CsA损伤组、CsA与p38激酶抑制剂合用组、p38激酶抑制剂组、CsA与ERK1/2激酶抑制剂合用组和ERK1/2激酶抑制剂组。

MTT法检测各组 HKC增殖抑制率，ELISA法测定各组 HKC上清液中 KIM-1水平，流式细胞术检测各组细胞存活率、细胞凋亡率和细胞坏死率。

结果：与空白组比较，CsA损伤组细胞上清液中KIM-1水平显著升高（P＜0.05），细胞存活率显著降
低（P＜0.05），细胞凋亡率和细胞坏死率显著升高（P＜0.05）；p38激酶抑制
剂组和 ERK1/2激酶抑制剂组中细胞存活率、细胞凋亡率和细胞坏死率比较差异无统计学意义（P＞0.05）。

与CsA损伤组比较，CsA与 p38激酶抑制剂合用组、CsA与 ERK1/2激酶抑制剂合用组细胞上清液中KIM-1水平显著降低（P＜
0.05），细胞存活率显著升高（P＜0.05），细胞凋亡率和细胞坏死率显著降低（P＜0.05）。

结论：p38 MAPK通路和ERK1/2 MAPK通路参与CsA素引起肾
小管上皮细胞培养液中KIM-1水平升高的过程，KIM-1的表达可能成为临床监测CsA肾毒性的生化指标。

【总页数】5页(P1201-1205)
【作者】宋莲莲;赵军;于金宇;张文岚;薛丽娟;傅耀文
【作者单位】吉林省中医药科学院病理室，吉林长春 130021; 吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021;吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021;吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021;吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021;吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021;吉林大学第一医院泌尿外科暨器官移植中心，吉林长春 130021
【正文语种】中文
【中图分类】R329.28
【相关文献】
1.草酸钙晶体引起肾小管上皮细胞紧密连接损伤与TRPV5变化的调节机制 [J], 卢穗琳;钟文;李淑珏;赵志健
2.肾脏缺血/再灌注损伤中肾小管上皮细胞凋亡机制的研究现状 [J], 乔晞;陈香美
3.尿中肾损伤分子1水平升高对大鼠早期肾损伤的预测作用 [J], 申俊;刘妍;张金晓;高绪聪;周飞;姜凌;张建军;张宗鹏
4.碘克沙醇对于肾功能不全大鼠肾损伤分子-1水平及肾小管上皮细胞凋亡率的影响 [J], 王娴君;吴尚勤;姚青海;董国峰
5.苏木酮A对顺铂引起人肾小管上皮细胞损伤的保护作用及其机制 [J], 康林; 赵静; 杨帆; 徐明堂; 王涛; 赵焕芬
因版权原因，仅展示原文概要，查看原文内容请购买。