辛伐他汀对大鼠肺成纤维细胞增殖和胶原合成的影响及意义

Effects of simvastatin on the proliferation and collagen systhesis of rat lung fibroblasts

目的探讨辛伐他汀(SIM)对肺成纤维细胞(LF)的增殖、胶原合成及基质金属蛋白酶-2(MMP-2)分泌的影响。方法用消化法培养新生SD大鼠的LF,给予不同浓度的SIM干预。四氮唑蓝(MTT)比色法检测细胞增殖,细胞免疫组化法测定细胞胶原的合成,ELISA法测定细胞培养上清液MMP-2的含量。结果随着SIM浓度(5,10,50μmol/L)的增高,MTT比色法A490值、LF表达Ⅰ、Ⅲ型胶原的平均光密度值(A)及培养上清液中的MMP-2含量均呈递减的趋势,与对照组相比,差异均非常显著(均P<0.01)。加入200μmol/L甲羟戊酸可明显拮抗此作用(P<0.01)。均具有统计学意义。结论降脂药物SIM具有抑制基本的成纤维细胞生长因子促LF增殖和胶原合成的作用,并可减少MMP-2的分泌,抑制LF黏附迁移功能,可能对防止肺移植术后闭塞性细支气管炎有一定的潜在临床应用价值。

Objective To investigate the effects of simvastatin on the proliferation, collagen synthesis and matrix metalloproteinase （MMP-2） excretion of rat lung fibroblasts （LFs）. Methods Lung fibroblasts of Sprague- Dawley （SD） rats were isolated and cultured. Lung fibroblast proliferation was measured by thiazolyl blue （MTT） assay. Collagen synthesis was examined immunocytochemically. Matrix metalloproteinase （MMP-2） protein in the conditioned media was determined by ELISA. Results In the 5,10 and 50μmol/L simvastatin groups, the A490 value of MTT colorimetry, A value of collagen in LFs and MMP-2 protein in the conditioned media were significantly lower than those in the control group （all P〈0.01）. This effect could be blocked by the addition of mevalonate （200μmol/ L）. Conclusion Simvastatin inhibits effectively the proliferation of cultured rat LFs, the collagen systhesis and MMP-2 excretion. Further study of statins as the potential therapeutic medicines for obliterative bronchiolitis is necessary.