| 辛伐他汀对大鼠肺成纤维细胞功能及其抑制通路的影响(英文) | |
| 奚吉成 ; 吴清玉 ; 陈连凤 ; Xi Ji-cheng ; Wu Qing-yu ; Chen Lian-feng | |
| 2010-06-09 ; 2010-06-09 | |
| 关键词 | 成纤维细胞/药物作用 肺/细胞学 斯伐他汀/药理学 R965 |
| 其他题名 | Simvastatin for lung fibroblast function and its inhibitory pathway in rats |
| 中文摘要 | 背景:他汀类药物可以通过阻断甲羟戊酸的合成,抑制某些膜联结蛋白的翻译后修饰,从而阻断某些细胞内信号传导通路,抑制多种细胞的增殖。目的:探讨辛伐他汀对肺成纤维细胞的增殖、胶原合成及基质金属蛋白酶2分泌的影响。设计:完全随机设计,对照实验。单位:中国协和医科大学阜外心血管病医院器官移植研究室。材料:实验于2004-06/2004-10在中国协和医科大学北京协和医院心内科实验室完成。培养的新生SD大鼠的肺成纤维细胞,根据培养液中加入的干预药物浓度不同而分为辛伐他汀0,1,5,10,50μmol/L及辛伐他汀50μmol/L+甲羟戊酸200μmol/L组。方法:用消化法培养新生SD大鼠的肺成纤维细胞,给予不同浓度的辛伐他汀干预。四氮唑蓝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,酶联免疫吸附法测定细胞培养上清液基质金属蛋白酶2的含量。主要观察指标:不同浓度辛伐他汀及辛伐他汀加甲羟戊酸干预后肺成纤维细胞增殖和胶原合成能力,以及基质金属蛋白酶2分泌量。结果:①辛伐他汀5,10,50μmol/L组四氮唑蓝比色A490值,肺成纤维细胞表达Ⅰ,Ⅲ型胶原的平均吸光度值(A值)及培养上清液中的基质金属蛋白酶2含量明显低于辛伐他汀0μmol/L组(0.520±0.010,0.334±0.011,0.260±0.012,0.111±0.011;0.508±0.011,0.324±0.014,0.232±0.015,0.083±0.015;0.445±0.017,0.305±0.015,0.216±0.015,0.068±0.012;0.561±0.013,0.361±0.012,0.289±0.012,0.140±0.013,t=3.359～8.111,P<0.05～0.01)。②辛伐他汀50μmol/L+甲羟戊酸200μmol/L组四氮唑蓝比色A490值,肺成纤维细胞表达Ⅰ,Ⅲ型胶原的平均吸光度值(A值)及培养上清液中的基质金属蛋白酶2含量明显高于辛伐他汀50μmol/L组(0.567±0.015,0.354±0.014,0.283±0.012,0.138±0.011,t=4.715～10.950,P<0.01)。结论:辛伐他汀能抑制肺成纤维细胞增殖和胶原合成,并可减少基质金属蛋白酶2的分泌,抑制肺成纤维细胞黏附迁移功能,并可通过影响甲羟戊酸通路而具有抗细胞增殖作用。; BACKGROUND: Statins can block many intracellular signal transductive pathways and suppress the proliferation of various cells by affecting the synthesis of mevalonic acid and the translation following modification of some membrane connecting proteins.OBJETCIVE: To investigate the influence of simvastatin on the proliferation of lung fibroblasts,the synthesis of collagen and the secretion of matrix metalproteinase 2(MMP 2).DESIGN: Completely randomized controlled study.SETTING: At Organ Transplanting Research Institute of Fuwai Cardiovasular Diseases Hospital,Peking Union Medical College.MATERIALS: This study was carried out at the Laboratory of Cardiology of Beijing Union Medical College hospital,Peking Union Medical College from June 2004 to October 2004.Lung fibroblasts derived from neonatal SD rats were co cultured in vitro with different dosage of simvastatin of 0,1,5,10,50 μ mol/L,and 50 μ mol/L simvastatin+ 200 μ mol/L mevalonic acid.METHODS: Lung fibroblasts deriving from neonatal SD rat were co cultured with different dosage of simvastatine in vitro.Methyl thiazolyl tetrazolium colorinetry was used to detect the cell proliferation,and cell immunohistochemical assay was used to determine the collagen synthesis and meanwhile,MMP 2 content in supernatant was examined with enzyme linked immunosorbent assay.MAIN OUTCOME MEASURES: The proliferation of fibroblasts,the synthesis of collagen and the secretion of MMP 2 due to different dosage of simvastatin intervention and simvastatin combined with mevalonic acid.RESULTS: ① MTT colorimetric A490 value, the mean absorbency( A value) presenting the expression of typeⅠ , Ⅲ of collagen in lung fibroblasts and the level of MMP 2 in 5, 10, 50 μ mol/L simvastatin group were obviously lower than those of 0 μ mol/L simvastatin group(0.520± 0.010,0.334± 0.011,0.260± 0.012,0.111± 0.011;0.508± 0.011,0.324± 0.014,0.232 ± 0.015,0.083± 0.015;0.445± 0.017,0.305± 0.015,0.216± 0.015,0.068± 0.012;0.561± 0.013,0.361± 0.012,0.289± 0.012,0.140 ± 0.013,t=3.359- 8.111,P< 0.05- 0.01).② MTT colorimetric A490 value, the mean absorbency( A value) in lung fibroblasts and the level of MMP 2 in 50 μ mol/L simvastatin+ 200 μ mol/L mevalonic acid group were obviously higher than that of the 50 μ mol/L simvastatin group(0.567 ± 0.015,0.354± 0.014,0.283± 0.012,0.138± 0.011,t=4.715 - 10.950,P< 0.01).CONCLUSION: Simvastatin could suppress the fibroblast proliferation and collagen synthesis,attenuate the secretion of MMP 2 and suppress consequently the adhesion and migration of lung fibroblasts;moreover,it has the capability of anti cell proliferation by affecting the mevalonic acid pathway. |
| 语种 | 英语 ; 英语 |
| 内容类型 | 期刊论文 |
| 源URL | [http://hdl.handle.net/123456789/59138]  |
| 专题 | 清华大学 |
| 推荐引用方式 GB/T 7714 | 奚吉成,吴清玉,陈连凤,等. 辛伐他汀对大鼠肺成纤维细胞功能及其抑制通路的影响(英文)[J],2010, 2010. |
| APA | 奚吉成,吴清玉,陈连凤,Xi Ji-cheng,Wu Qing-yu,&Chen Lian-feng.(2010).辛伐他汀对大鼠肺成纤维细胞功能及其抑制通路的影响(英文).. |
| MLA | 奚吉成,et al."辛伐他汀对大鼠肺成纤维细胞功能及其抑制通路的影响(英文)".(2010). |
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