辛伐他汀对烟雾暴露大鼠肺泡上皮细胞的作用

目的 探讨辛伐他汀对烟雾暴露大鼠肺气肿肺泡上皮细胞及血管内皮生长因子(VEGF)表达的影响.方法 24只12周龄健康雌雄各半Wistar大鼠随机数字表法分为对照组、烟雾组、药物组和烟雾+药物组(烟+药组),每组6只,同步饲养16周,雌雄大鼠同步、分箱饲养16周.分别采用逆转录PCR法测定肺组织中VEGF的mRNA表达,酶联免疫吸附法测定BALF和组织中VEGF含量,免疫组织化学二步法检测VEGF和增殖细胞核抗原(PCNA)表达水平.多组间比较采用单因素方差分析,两两比较采用LSD-t检验.结果 烟+药组大鼠肺泡上皮细胞PCNA阳性细胞构成比(10.3±2.0)%]明显高于烟雾组(4.8±0.8)%];BALF和组织匀浆中VEGF水平(187±15)ng/L和(6782±50)ng/L]接近于对照组(200±20)ng/L和(7558±330)ng/L],明显高于烟雾组(71±16)ng/L和(4149±110)ng/L];肺泡和支气管上皮细胞中VEGF表达(67.7±5.0)%和(49.0±3.0)%]近似于对照组(68.3±3.3)%和(51.3±2.9)%],明显高于烟雾组(27.0±5.9)%和(16.3±2.7)%].烟+药组与烟雾组比较,差异均有统计学意义(t值为1.117～12.001,均P＜0.01).结论 辛伐他汀可部分促进肺泡上皮细胞增殖,提高肺组织中VEGF含量及肺泡上皮细胞表达,延缓烟雾暴露所致大鼠肺气肿的进展.

The effect of simvastatin on alveolar epithelial cells in cigarette smoking-induced emphysema

Objective To explore the effect of simvastatin on alveolar epithelial cells and the expression of vascular endothelial growth factor (VEGF) in cigarette smoking-induced emphysema in rats.Methods Twenty-four,12-week-old healthy male and female Wistar rats were randomly divided into 4 groups of 6 each: a control (W) group,a smoking (Sm) group,a simvastatin (St) group,and a smoking-simvastatin (SmSt) group.The rats were simultaneously fed,and kept in individual cages for 16 weeks.The VEGF level in lung tissue and bronchoalveolar lavage fluid (BALF) of each group was measured by ELISA.The expression of VEGF mRNA was determined by RT-PCR.The expressions of VEGF and proliferating cell nuclear antigen (PCNA) were determined by two-step immunohistochemistry assay.Oneway ANOVA and LSD-t test were used for statistical analysis.Results The percentage of PCNA-positively stained alveolar epithelial cells was significantly higher in the SmSt group ( 10.3±2.0) %] than in the Sm group (4.8 ± 0.8)%].The levels of VEGF in BALF and lung tissue homogenate of the SmSt group (187 ±15) ng/L and (6782 ±50) ng/L] were similar to the W group (200±20) ng/L and (7558 ±330) ng/L],but were significantly higher than that in the Sm group (71±16) ng/L and (4149±110)ng/L].VEGF expression in alveolar and bronchial epithelial cells of rats in the SmSt group (67.7 ±5.0)% and (49.0 ±3.0)%],was similar to the W group (68.3 ±3.3)% and (51.3 ±2.9)%].But the level of VEGF expression was significantly increased as compared to that in the Sm group ( 27.0 ±5.9) % and ( 16.3 ± 2.7) %].SmSt group vs Sm group t = 1.117 - 12.001,all P ＜ 0.01.Conclusions Simvastatin ameliorated the development of cigarette smoke-induced COPD in rats,partly by promoting alveolar epithelial cell proliferation and up-regulating the expression of VEGF.