辛伐他汀对老年COPD大鼠肺泡上皮细胞凋亡的干预作用

目的：探讨辛伐他汀对老年COPD大鼠肺泡上皮细胞凋亡干预作用。方法39只老年Wistar大鼠随机分为正常组（A组）、COPD模型组（B组）及辛伐他汀干预组（C组），每组各13只。B、C组采用熏香烟联合气道内滴入脂多糖法建立大鼠COPD模型，在造模2周后C组给予辛伐他汀（2.5 mg/kg）灌胃6周，A、B组给予同等量生理盐水灌胃。8周后处死大鼠，并观察大鼠肺组织病理变化，检测肺泡上皮细胞凋亡及凋亡相关因子半胱氨酸蛋白酶-3（Caspase-3）、诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS） mRNA表达，并计算凋亡指数。结果与A组相比， B组和C组凋亡指数、Caspase-3及iNOS mRNA表达增加（P均＜0.01），eNOS mRNA表达降低（P＜0.01）；与B组相比，C组凋亡指数、Caspase-3及iNOS mRNA表达降低（P均＜0.01），eNOS mRNA表达增加（P＜0.01）。各组间肺泡上皮细胞凋亡指数与Caspase-3及iNOS mRNA表达呈正相关（P＜0.05），与eNOS mRNA表达呈负相关（P＜0.05）。各组间Caspase-3 mRNA与iNOS mRNA表达呈正相关（P＜0.05），与eNOS mRNA表达呈负相关（P＜0.01）。结论辛伐他汀通过增加肺组织eNOS基因表达，抑制iNOS及Caspase-3基因表达，抑制了老年COPD大鼠肺泡上皮细胞凋亡。

Simvastatin attenuates the apoptosis of alveolar epithelial cells in aged chronic obstructive pulmonary disease rats

Objective To explore the effect of simvastatin on the apoptosis of alveolar epithelial cells in aged chronic obstructive pulmonary disease （COPD）model rat lungs. Methods Thirty-nine aged wistar rats were randomly divided into three groups：the normal group （group A,n=1 3 ）,the COPD model group （group B,n=1 3）and the simvastatin treatment group （group C,n=1 3）. The COPD rat model was estab-lished by cigarette smoke combined with lipopolysaccharide. Simvastatin,at a dose of （2.5 mg/kg）,was ad-ministered orally to rats in group C once per day for 6 weeks. Meanwhile,Group A and B received equivalent normal saline. At the end of the 8 weeks,rats were sacrificed after the simvastatin therapy. Thereafter,the pathological changes of lung tissue were observed,and the alveolar epithelial cell apoptosis was detected. The apoptosis related factors Caspase-3,endothelial nitric oxide synthase （eNOS）and inducible nitric oxide syn-thase （iNOS）were determined. In addition,the apoptosis index （AI）was calculated. Results In group B and C,the AI and expression of Caspase-3 and iNOS mRNA increased significantly （P＆lt;0.01 ）,whereas the expression of eNOS mRNA decreased （P＆lt;0.01 ）compared with group A. In group C,the AI and expression of Caspase-3 and iNOS mRNA decreased significantly （P＆lt;0.01 ）,and the expression of eNOS mRNA in-creased （P＆lt;0.01 ）compared with group B. In addition,The AI was positively correlated with Caspase-3 and iNOS expression,（P＆lt;0.05 ）and negatively correlated with eNOS mRNA （P＆lt;0.05 ）. Caspase-3 mRNA ex-pression was identified to be positively correlated with iNOS mRNA expression （P＆lt;0.05 ）,and negatively cor-related with eNOS mRNA （P＆lt;0.01 ）expression in all groups. Conclusion Simvastatin could attenuate the alveolar epithelial cells apoptosis in aged COPD rat lungs and this mechanism may be associated with the up-regulated expression of eNOS mRNA and down-regulated expression of iNOS and Caspase-3 in lung tissues.