褐藻多糖硫酸酯对TGF-β1孵育的人肾小球系膜细胞MMP-2、TIMP-2表达的影响  

Effects of Fucoidan on the expression of MMP2 and TIMP-2 in human mesangial cells cultured with growth factor β1

作　　者：贺玉珍[1] 张李梅 牟授菡[3] 吕丛奎[3] 鞠建伟[3] 

机构地区：[1]滨州医学院中西医结合学院,烟台264003 [2]乳山市人民医院 [3]烟台经济技术开发区医院

出　　处：《滨州医学院学报》2012年第2期104-107,共4页Journal of Binzhou Medical University

摘　　要：目的观察褐藻多糖硫酸酯(Fucoidan FPS)对TGF-β1下刺激人肾小球系膜细胞MMP-2、TIMP-2分泌的影响,探讨其在慢性肾衰竭(Chronic Renal Failure CRF)防治中的意义。方法用TGF-β1作为刺激因子,孵育体外培养的人肾小球系膜细胞(Human Mesangial cell HMC),并分别用不同浓度的FPS干预,具体分组如下:模型组(TGF-β14 ng/ml)、FPS高剂量组(TGF-β14 ng/ml+FPS 100 ug/ml)、FPS中剂量组(TGF-β14 ng/ml+FPS 50 ug/ml)、FPS低剂量组(TGF-β14 ng/ml+FPS25 ug/ml)、FPS对照组(FPS 100ug/ml)、正常对照组。ELISA技术检测HMC培养上清液中MMP-2、TIMP-2蛋白表达水平,Re-altime PCR技术检测HMC的MMP-2、TIMP-2 mRNA表达水平。结果与正常对照组相比,TGF-β1能减少HMC的MMP-2蛋白及mRNA表达(P<0.01),增加HMC的TIMP-2蛋白及mRNA表达(P<0.01);FPS能阻断TGF-β1刺激下HMC的MMP-2蛋白及mRNA表达减少、TIMP-2蛋白及mRNA表达增加(P<0.01,P<0.05);FPS对照组与正常对照相比MMP-2、TIMP-2蛋白及mRNA表达差异无统计学意义(P>0.05)。结论褐藻多糖硫酸酯能阻断TGF-β1刺激下人肾小球系膜细胞MMP-2、TIMP-2表达的比例失衡,阻断了由MMP-2、TIMP-2比例失衡导致的ECM积聚,从而延缓了慢性肾衰竭的进展。Objective To investigate the effective of Fucoidan（ FPS ） on the secretion of MMP-2 and TIMP-2 in human mesangial ceils （ HMC ） which induced by growth factor β1 and to explore its mechanism of kidney protecting in chronic renal failure. Methods HMC were cultured in vitro with TGF-β1, and treated with different concentration of FPS, and the cells were divided into 6 groups： model group （ TGF-β1：4ng/ml ）, high-FPS group （ TGF-β1 ：4ng/ml ＋ FPS ： 100 ug/ml ）, medium-FPS group （ TGF-β1：4ng/ml ＋ FPS： 50 ug/ml} ,low-FPS group（ TGF-β1 ： 4 ng,/ml ＋ FPS ：25 ug/ml}, FPS control group （FPS-100 ug/ml） and blank control group. The level of MMP-2 and TIMP-2 protein expression was measured by ELISA, The level of MMP-2 and TIMP-2 mRNA expression was measured by Reshime-PCR. Results With the stimulation of TGF-β1, the expression of MMP-2 protein and mRNA was decreased signifi- candy （ P 〈 0. 01） , which then were increased by the treatment of FPS （ P 〈 0. 01 ） , and showed dose dependent manner; the expression of T1MP-2 protein and mRNA was increased significantly （P 〈 0. 01 ） , which then were decreased by the treatment of FPS （ P 〈 0.01 ） , and showed dose dependent manner too. Compared with blank control group MMP-2 and TIMP-2 protein and mRNA expression in FPScontrol group was not statistically significant （ P 〉 0. 05）. Conclusion The disbananlance of MMP-2 and TIMP-2 in HMC may be induced by TGF-β1 and FPS can block the alteration . Thus, the accumulation of Extracelluar matrix（ ECM） and glomerulosclerosis can be prevented.

关 键 词：人肾小球系膜细胞 褐藻多糖硫酸酯 转化生长因子-Β1 基质金属蛋白酶 金属蛋白酶组织抑制因子 

分 类 号：R692.6[医药卫生—泌尿科学] R362[医药卫生—外科学]