[1]李 均,杨晓娟,冉 阳,等.霉酚酸酯对狼疮性肾炎小鼠肾小球系膜细胞增殖、炎性反应的影响及分子机制研究[J].陕西医学杂志,2023,52(8):973-976,991.[doi:DOI:10.3969/j.issn.1000-7377.2023.08.007]
　LI Jun,YANG Xiaojuan,RAN Yang,et al.Effect of mycophenolate mofetil on proliferation and inflammatory response of glomerular mesangial cells in lupus nephritis mice and its molecular mechanism[J].,2023,52(8):973-976,991.[doi:DOI:10.3969/j.issn.1000-7377.2023.08.007]
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霉酚酸酯对狼疮性肾炎小鼠肾小球系膜细胞增殖、炎性反应的影响及分子机制研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年8期
页码:
973-976,991
栏目:
基础研究
出版日期:
2023-08-05

文章信息/Info

Title:
Effect of mycophenolate mofetil on proliferation and inflammatory response of glomerular mesangial cells in lupus nephritis mice and its molecular mechanism
作者:
李 均1; 杨晓娟1; 冉 阳1; 肖 骏1; 郝 培2
(1.重庆市急救医疗中心 重庆市第四人民医院,重庆400014; 2.青岛市城阳区人民医院,山东 青岛266109)
Author(s):
LI Jun; YANG Xiaojuan; RAN Yang; XIAO Jun; HAO Pei
(Chongqing Emergency Medical Center,Chongqing 400014,China)
关键词:
狼疮性肾炎;  肾小球系膜细胞;  霉酚酸酯;  miR-455-3p;  细胞增殖;  细胞凋亡;  炎性反应
Keywords:
Lupus nephritis;  Glomerular mesangial cells;  Mycophenolate mofetil;  miR-455-3p;  Cell proliferation;  Apoptosis;  Inflammatory reaction
分类号:
R 593.24
DOI:
DOI:10.3969/j.issn.1000-7377.2023.08.007
文献标志码:
A
摘要:
目的:探究霉酚酸酯(MMF)抑制狼疮性肾炎(LN)肾小球系膜细胞(GMC)增殖及炎性反应的分子机制。方法:分离、培养LN细胞,将细胞分为:对照组,LN组,0.01 μmol/L MMF组,0.1 μmol/L MMF组,1.0 μmol/L MMF组,转染miR-NC+LN组,转染miR-455-3p+LN组,转染anti-miR-NC+0.1 μmol/L MMF组,转染anti-miR-455-3p+0.1 μmol/L MMF组。用实时荧光定量PCR(RT-qPCR)法检测各组细胞中miR-455-3p的相对表达水平; 用CCK-8法、流式细胞术、酶联免疫法(ELISA)、蛋白免疫印迹法(Western blot)分别检测各组细胞的增殖、凋亡率及肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)水平,活化型半胱氨酸天冬氨酸蛋白酶-3(Cleaved caspase-3)蛋白表达水平。结果:与对照组比较,LN组miR-455-3p相对表达水平、细胞凋亡率以及Cleaved caspase-3蛋白表达水平显著降低(均P<0.05),细胞增殖,TNF-α、IL-1β表达水平显著升高(均P<0.05); 与LN组比较,0.01 μmol/L MMF组、0.1 μmol/L MMF组以及1.0 μmol/L MMF组细胞增殖和炎症因子表达水平降低(均P<0.05),miR-455-3p、细胞凋亡率以及Cleaved caspase-3蛋白表达水平升高(均P<0.05),miR-455-3p+LN组与miR-NC+LN比较,细胞增殖和炎症因子表达水平降低(均P<0.05),miR-455-3p表达,凋亡率以及Cleaved caspase-3蛋白水平显著升高(均P<0.05); 与anti-miR-NC+0.1 μmol/L MMF组比较,anti-miR-455-3p+0.1 μmol/L MMF组miR-455-3p表达,凋亡率及Cleaved caspase-3蛋白表达显著降低,细胞增殖和炎症因子表达水平显著升高(均P<0.05)。结论:MMF能够抑制LN肾小球系膜细胞的增殖和炎性反应、促进凋亡、改善LN,这一作用与miR-455-3p的表达调控有关。
Abstract:
Objective:To explore the molecular mechanism of mycophenolate mofetil(MMF)inhibiting the proliferation and inflammatory response of glomerular mesangial cells(GMC)in lupus nephritis(LC).Methods:The isolated and cultured MCs of LN mice were divided into control group,LN model group,0.01 μmol/L MMF group,0.1 μmol/L MMF group,1.0 μmol/L MMF group,miR-NC+LN group,miR-455-3p+LN group,anti-miR-NC+0.1 μmol/L MMF group,anti-miR-455-3p+0.1 μmol/L MMF group.The relative expression levels of miR-455-3p were detected by RT-qPCR.CCK-8 method,flow cytometry,ELISA,Western blot were used to detect the proliferation,apoptosis rate,the expression levels of TNF-α,IL-1β and Cleaved caspase-3 protein were analyzed.Results:Compared with the control group,the relative expression level of miR-455-3p,apoptosis rate and the expression level of Cleaved caspase-3 protein in the LN model group were significantly decreased,the cell proliferation and the levels of TNF-α and IL-1β were significantly increased(all P<0.05).Compared with the LN model group,the 0.01 μmol/L MMF group,0.1 μmol/L MMF group and 1.0 μmol/L MMF group had decreased cell proliferation and inflammation level,and the expression level of miR-455-3p,apoptosis rate and the expression level of Cleaved caspase-3 protein increased(all P<0.05).Compared with miR-NC+LN group,the cell proliferation and the expression levels of inflammatory factors in miR-455-3p+LN group were decreased,while the expression of miR-455-3p,apoptosis rate and Cleaved caspase-3 protein level were significantly increased(all P<0.05).Compared with the anti-miR-NC+0.1 μmol/L MMF group,the anti-miR-455-3p+0.1 μmol/L MMF group showed significantly lower miR-455-3p expression,apoptosis rate and Cleaved caspase-3 protein expression,while the cell proliferation and inflammation levels were significantly increased(all P<0.05).Conclusion:Mycophenolate mofetil can inhibit the proliferation and inflammatory reaction of LN glomerular mesangial cells,promote apoptosis,and improve LN,which is related to the regulation of miR-455-3p expression.

参考文献/References:

[1] 朱安琪,刘春莹.刘春莹主任医师治疗狼疮性肾炎经验摭拾[J].陕西中医,2020,41(7):951-953.
[2] 张彦平,贺军涛,殷 鉴,等.尿液免疫球蛋白轻链检测对系统性红斑狼疮肾脏损伤的诊断价值[J].陕西医学杂志,2020,49(9):1172-1174.
[3] 刘 刚,任国臣,杨晓萍.活性维生素D3对人肾小球系膜细胞Bcl-2、Bax蛋白表达的影响[J].现代中西医结合杂志,2021,30(35):3900-3904.
[4] 江碧玲,李 延,陶 娟.霉酚酸酯在皮肤科的应用进展[J].实用皮肤病学杂志,2022,15(2):98-104.
[5] Liu PP,Zhao L,Gu YX,et al.lncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway[J].Respir Res,2021,22(1):44.
[6] Gu QQ,Wang B,Zhao HY,et al.lncRNA promoted inflammatory response in ischemic heart failure through regulation of miR-455-3p/TRAF6 axis[J].Inflamm Res,2020,69(7):667-681.
[7] Gong HX,Wan XW,Zhang Y,et al.Downregulation of HOTAIR reduces neuronal pyroptosis by targeting miR-455-3p/NLRP1 axis in propofol-treated neurons in vitro[J].Neurochem Res,2021,46(5):1141-1150.
[8] 罗 玮,刘 玲,戴丽星,等.加味涤痰汤对卒中后认知障碍患者外周血miRNAs组合表达的影响研究[J].吉林中医药,2022,42(3):302-306.
[9] 罗慧臣,胡丹慧,张 济.miR-143-3p靶向TREM1基因对狼疮性肾炎小鼠肾小球系膜细胞炎性因子分泌及凋亡的调控机制[J].中国免疫学杂志,2020,36(4):399-410.
[10] 刘春雅,金 晶,李玉芳,等.miR-21靶向PTEN调节PI3 K/AKT通路对狼疮性肾炎患者肾小球系膜细胞增殖及炎性因子分泌的影响[J].中国中西医结合肾病杂志,2021,22(9):759-764.
[11] 赵亚峰,边 静,李娜梅,等.狼疮性肾炎患者中医证型与临床病理分析[J].陕西中医,2019,40(11):1555-1558.
[12] 辛雪艳,杨丛旭.许家松教授治疗狼疮性肾炎经验撷英[J].世界中西医结合杂志,2021,16(12):2213-2216.
[13] 张天舒,吕 静,栾 佳,等.芪蓟肾康汤对AngⅡ诱导人肾小球系膜细胞分泌肿瘤坏死因子-α、转化生长因子-β1的影响[J].长春中医药大学学报,2020,36(6):1167-1171.
[14] 吴洪銮,安 宁,陈小翠,等.调节M2型丙酮酸激酶对TGF-β1诱导人肾小管上皮细胞周期阻滞和细胞外基质分泌的影响[J].临床肾脏病杂志,2021,21(12):1009-1014.
[15] 马洪波,董燕娇,孙 琨,等.lncRNA TUG1吸附microRNA-144对狼疮肾炎小鼠肾小球系膜细胞炎症因子分泌与凋亡的影响及其机制研究[J].中国现代医学杂志,2022,32(3):1-9.
[16] 刘 欢,丁 宁,田 丽,等.霉酚酸酯诱导治疗对狼疮性肾炎患者Treg/Th17的影响[J].标记免疫分析与临床,2021,28(12):2140-2146.
[17] Dehkordi M,Tashakor A,Connell E,et al.Apoptosome-dependent myotube formation involves activation of caspase-3 in differentiating myoblasts[J].Cell Death Dis,2020,11(5):308.
[18] 彭婷婷,刘海燕,肖 璐,等.重度子痫前期患者胎盘组织中Rab23的表达及对人胎盘滋养细胞凋亡及自噬的影响[J].中国医药,2021,23(3):431-435.
[19] Wen T,Wu H,Zhang L,et al.Circular RNA circ-0007142 regulates cell proliferation,apoptosis,migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer[J].Anticancer Drugs,2021,32(1):22-33.
[20] Han J,Xiong Y,Deng H,et al.miR-455-3p regulates glioma cell proliferation by targeting PAX6[J].Tropical Journal of Pharmaceutical Research,2021,18(4):689-695.
[21] 韦佩祺,苏梓健,梁 芳,等.microRNA在系统性红斑狼疮中的作用机制研究进展[J].陕西医学杂志,2023,52(2):238-240.
[22] 方丽纳,张 博,平丽英,等.霉酚酸酯的临床应用进展[J].发酵科技通讯,2021,50(1):14-19.

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备注/Memo

备注/Memo:
基金项目:重庆市自然科学基金资助面上项目(CSTC2021JCYJ-MSXMX1061)
更新日期/Last Update: 2023-08-07