辛伐他汀对老年COPD大鼠肺泡上皮细胞凋亡的干预作用

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

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。

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.