不同饲养方式和烟草烟雾暴露所致大鼠肺气肿对动脉粥样硬化形成的影响

摘要

目的 探讨不同饲养方式和烟草烟雾暴露所致肺气肿与动脉粥样硬化形成的关系及可能的机制.方法 将48只大鼠按烟草烟雾暴露与否和不同饲养方式数字抽签随机均分为普通饲料+烟草烟雾暴露组、高脂饲料+烟草烟雾暴露组、限制摄入+烟草烟雾暴露组、普通饲料组、高脂饲料组和限制摄入组(各8只).24周后测大鼠Lee's指数,酶联免疫吸附法测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和脂联素水平,显微镜下测肺组织平均内衬间隔(MLI)和平均肺泡数,观察主动脉粥样硬化病理学改变,免疫组化法测主动脉血管内皮生长因子(V EG F)和骨形态发生蛋白2(BM P-2)水平.结果 烟草烟雾暴露及高脂、限制饲养方式组大鼠肺气肿明显.镜下观察主动脉,非烟草烟雾暴露组无动脉粥样硬化,烟草烟雾暴露组可见早期动脉粥样硬化改变.烟草烟雾暴露和不同饲养方式对血清脂联素有交互作用(F=10.68,P<0.05),烟草烟雾暴露组主动脉VEGF和BMP-2水平均与MLI、血清TNF-α和IL-6水平呈正相关,与肺泡数呈负相关(r值分别为0.431、0.471、0.448、0.449、0.428、0.447、-0.411、-0.442;均P<0.05).结论 烟草烟雾暴露和不同饲养方式均可影响肺气肿形成,肺气肿严重程度与动脉粥样硬化程度呈正相关,系统性炎症反应可能参与其中.%Objective To explore the relationship and its mechanism of emphysema induced by different ways of rearing and tobacco smoke exposure with the atherosclerosis formation. Methods Forty-eight SD rats were randomly divided into 6 groups (n= 8 ,each):a normal diet + tobacco smoke exposure (TSE) group ,a fat-rich diet + TSE group ,a limit intake + TSE group ,a normal diet group ,a fat-rich diet group ,and a limit intake group for 24 weeks. Lee's index ,serum tumor necrosis factor-α (TNF-α) ,interleukin-6 (IL-6 ) ,adiponectin (APN ) levels ,mean linear intercept (MLI) ,mean alveoli number (MAN) ,the aortic pathology change ,vascular endothelial growth factor (VEGF) of aorta ,and bone morphogenetic protein-2 (BMP-2) level were collected. Results Tobacco smoke exposure ,fat-rich diet ,and limit intake increased the severity of emphysema. The microscopic features of aorta showed an early atherosclerosis in the tobacco smoke exposure groups , but no atherosclerosis in the non-smoking groups. Interactions between tobacco smoke exposure and different ways of rearing on serum APN level (F= 10.68 ,P< 0.05) were found.In the tobacco smoke exposure groups ,Pearson correlation analysis showed positive correlations of aortic VEGF and BMP-2 levels with MLI ,serum TNF-α and IL-6 levels (r= 0.431 ,0.471 ,0 ,448 ,0.449 ,0.428 , 0.447 ,all P<0.05) ,and an negative correlation with MAN (r= -0.411 ,-0.442 ,P<0.05). Conclusions Both tobacco smoke exposure and different ways of rearing can influence the formation of emphysema. There is a positive correlation between the severities of emphysema and atherosclerosis , and systemic inflammation may be involved.