辛伐他汀对COPD大鼠肺组织凋亡相关因子的影响  

Effect of simvastatin on lung apoptotic factor in chronic obstructive pulmonary disease rat models

作　　者：丁启翠[1] 王伟[1] 王永彬[1] 陈旭东[2] 吴倩[1] 

机构地区：[1]山东大学第二医院呼吸科,济南250033 [2]山东省交通医院呼吸科,济南250031

出　　处：《山东大学学报（医学版）》2012年第6期65-69,共5页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助项目(Y2008C19)

摘　　要：目的探讨辛伐他汀对慢性阻塞性肺疾病(COPD)模型大鼠肺组织凋亡相关因子的影响及作用机制。方法随机将30只大鼠分为正常组、对照组、治疗组。对照组采用熏香烟加气管内滴入LPS法建立大鼠COPD模型,香烟暴露2周后治疗组同时给予辛伐他汀(2.5 mg/kg)治疗6周,8周后处死所有大鼠,HE染色观察大鼠肺组织病理改变,显微图像分析系统计算肺平均内衬间隔和平均肺泡数,免疫组织化学技术检测大鼠肺组织半胱氨酸蛋白酶-3(Caspase-3)、诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)的水平。结果对照组可见肺气肿和气道周围炎性改变,治疗组症状较对照组减轻;与正常组相比,对照组和治疗组肺平均内衬间隔(MLI)、iNOS、Caspase-3增多(P<0.05),平均肺泡数(MAN)、eNOS减少(P<0.05);与对照组比较,治疗组MLI、iNOS、Caspase-3减少(P<0.05),MAN、eNOS增多(P<0.05)。各组大鼠肺组织中Caspase-3与iNOS呈正相关(P<0.05),与eNOS呈负相关(P<0.05)。结论辛伐他汀通过增加肺组织eNOS表达,降低iNOS及Caspase-3表达,减少COPD肺组织细胞凋亡,在COPD中起到保护性作用。Objective To determine the effect and mechanism of simvastatin on lung apoptotic factors in chronic ob- structive pulmonary disease（COPD） rat models. Methods 30 rats were randomly divided into three groups： the normal group, the control group and the treatment group. The control group was treated by being exposed to smoking and intra- tracheal instillation of lipopolysaccharide to establish the COPD rat models. 2 weeks later, the treatment group was trea- ted with 2.5 mg/kg simvastatin daily for 6 weeks. The rats were executed after 8 weeks. Lung tissue sections stained by hematoxylin and eosin （HE） were observed, and mean linear intercept as well as mean alveolar numbers were measured by micrographical analysis. Expressions of eNOS, iNOS and caspase-3 were measured by immunohistochemistry. Results Emphysema and airway inflammation were observed in the control group, and the symptoms of the treatment group were lighter. Compared with the normal group, the mean linear intercept（ MLI）, iNOS, Caspase-3 in the control and treatment groups increased（ P 〈 0.05 ）, and the mean alveolar numbers （MAN） and eNOS decreased（ P 〈 0.05 ）. Compared with the control group, the MLI, iNOS, Caspase-3 decreased（ P 〈 0.05 ） and the MAN and eNOS increased （P 〈 0.05） in the treatment group. Caspase-3 in the lung tissue of each group positively correlated with iNOS （ P 〈 0.05 ）, and negatively with eNOS （ P 〈 0.05 ）. Conclusion Simvastatin has a protective effect on the COPD rat mod- els by increasing expression of eNOS and decreasing the expressions of iNOS and Caspase-3 which can reduce the apop- tosis of COPD lung tissue.

关 键 词：肺疾病 慢性阻塞性 细胞凋亡 辛伐他汀 大鼠 

分 类 号：R563.3[医药卫生—呼吸系统]