线粒体融合蛋白2与IgA1诱导的系膜细胞增殖及缬沙坦抗增殖作用的相关性研究  

Expression of mitofusin 2 in IgA1-induced glomerular mesangial cell proliferation and association with a valsartan-induced inhibitory effect on hyperplasia

作　　者：姜雪[1] 曾佳丽[1] 缪建霞 杜园园[1] 陈洪宇[1] 

机构地区：[1]杭州市中医院肾内科,310000

出　　处：《中国医师杂志》2018年第1期42-45,49,共5页Journal of Chinese Physician

基　　金：国家自然科学基金(81373631)~~

摘　　要：目的探讨IgA1诱导的系膜细胞增殖中线粒体融合蛋白2(Mfn2)、B淋巴细胞瘤-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)和半胱氨酸天冬氨酸蛋白酶-9(Caspase-9)的表达变化,及缬沙坦的抗细胞增殖作用与上述指标的相关性,为IgA肾病(IgAN)中系膜细胞增殖提供依据,为缬沙坦治疗IgAN、抑制系膜细胞增殖提供新的方向。方法将细胞分为实验组、对照组及药物治疗组,使用IgA1诱导大鼠系膜细胞增殖。使用CCK8检测各组细胞增殖水平,Real-time PCR检测Mfn2基因表达情况,Western blotting检测Mfn2、Bcl-2、Caspase-3和Caspase-9蛋白水平的表达变化。结果 IgA1可诱导大鼠系膜细胞增殖,随着系膜细胞增殖,Mfn2、Caspase-3和Caspase-9的蛋白表达明显降低,Bcl-2的蛋白表达明显升高。缬沙坦可抑制IgA1诱导的系膜细胞增殖,同时伴随Mfn2、Bcl-2、Caspase-3和Caspase-9的表达变化。结论缬沙坦可通过抑制系膜细胞增殖起到治疗IgA1诱导的系膜细胞增殖作用,且系膜细胞增殖变化与Mfn2、Bcl-2、Caspase-3和Caspase-9的蛋白表达有关。为IgA1诱导系膜细胞增殖及缬沙坦的抗增殖作用提供新的依据。Objective To observe glomerular mesangial cells （GMCs） proliferation induced by lgA1 and the association with the expression of apoptosis-related proteins-B cell lymphoma-2 （Bel-2）, eys- teine aspartie acid protease-3 （Caspase-3）, cysteine aspaItie acid protease-9 （Caspase-9） and with mito- fusin 2 （Mfn2） in rat GMCs, to study the possible mechanism of valsartan inhibiting rat GMCs prolifera- tion, and to provide a new direction for the mechanism of GMCs proliferation and intervention research in IgA nephrology （lgAN）. Methods GMCs stimulated with IgA1 were cultured in vitro to detect cell prolif- eration with the cell counting klt-8 cell activity assay （CCK8）. GMCs were divided into three groups： CG, TG and VG. The GMCs proliferation level was detected by the CCK8, using real-time PCR to detect Mfn2 expression and Western blotting to detect protein levels of Mfn2, Bcl-2, Caspase-3, and Caspase-9. Results Rat GMCs proliferated significantly after stimulation with IgAl, and IgA1 could obviously stimulate high expression of Bcl-2 in GMCs and down regulate the expression of Mfn2, Caspase-3, and Caspase-9. Valsar- tan could inhibit the proliferation of GMCs induced by IgA1 significantly, downregulate the expression of Bcl-2, and upregulate the expression of Mfn2, Caspase-3, and Caspase-9. Conclusions These results showed that the mechanism of action of valsartan in the treatment of IgAN is inhibiting the proliferation of GMCs. This mechanism may be associated with the regulation of apoptosis-related proteins, such as Mfit2, Bcl-2, Caspase-3, and Caspase-9. These findings may provide a new direction for the mechanism of GMCs proliferation and intervention research in IgAN.

关 键 词：线粒体蛋白质类/代谢 肾小球系膜细胞I病理学/代谢 免疫球蛋白A/副作用 缬 氨酸/类似物和衍生物/药理学 

分 类 号：R965[医药卫生—药理学]