EPA、DHA对脂多糖刺激大鼠系膜细胞表达MMPs、TIMPs及TGF-β1的影响

Effects of EPA and DHA on MMPs,TIMPs and TGF-β1 expression by lipopolysaccharide stimulated rat glomerular mesangial cells

目的观察二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)对脂多糖(LPS)刺激大鼠肾小球系膜细胞(GMC)表达基质金属蛋白酶(MMP)-2、MMP-9和金属蛋白酶组织抑制因子(TIMP)-1、TIMP-2以及转化生长因子-β1(TGF-β1)的影响。方法大鼠GMC与EPA、DHA(10,100μmol/L)作用48 h后,采用实时定量PCR方法检测MMP-2、MMP-9、TIMP-1和TIMP-2的mRNA表达,明胶酶谱法测定MMP-2、MMP-9活性,ELISA法测定TGF-β1含量。结果 EPA、DHA可以影响MMP、TIMP的表达,改善LPS诱导的MMP活力的降低,降低TGF-β1分泌。结论EPA、DHA可以通过改善MMP、TIMP失衡、减少TGF-β1分泌等机制,对损伤的GMC起保护作用。

Purpose To investigate the effects of eicosapentaenoic acid （EPA） and docosahexaenoic acid（DHA） on lipopolysaccharide （LPS） induced expression of matrix metalloproteinase-2,9 （ MMP-2, 9） , tissue inhibitor of metalloproteinases-1,2 （TIMP-1,2） and transforming growth factor-β1 （ TGB-β1 ） by LPS stimulated rat glomerular mesangial cells（GMCs）. Methods GMCs were incubated with EPA or DHA（10,100 μmol/L） for 48 hours,and the expression of MMP-2,9 and TIMP-1,2 mRNA was measured by real-time PCR method,the gelatinase activities were detected by gelatin zymography, and TGF-β1 was measured by ELISA. Results EPA and DHA could decrease the expression of MMPs and TIPMs by LPS stimulated GMCs, but increase the ratios of MMPs/TIPMs, and activities of MMPs. EPA and DHA could also decrease the production of TGF-β1. Conclusion The data suggest that EPA and DHA may protect GMCs by regulating the imbalance of MMPs and TIMPs,and reducing the production of TGF-β1.