诱导型NOS抑制可缓解烟草烟雾导致的大鼠肺气肿及肺动脉高压

Induction NOS inhibition can alleviate rats emphysema and pulmonary hypertension caused by tobacco smoke

目的:探究诱导型一氧化氮合酶(iNOS)抑制剂在缓解烟草烟雾导致的小鼠肺气肿及肺动脉高压中的效果。方法:选择60只健康SD大鼠,将其随机分为对照组、损伤组和干预组,每组各20只,其中对照组大鼠常规饲养,损伤组大鼠建立烟草烟雾损伤模型,干预组大鼠在建立模型后为其注射iNOS抑制剂,采集三组大鼠肺组织,观察其外形差异,对比三组大鼠肺组织匀浆中一氧化氮(NO)、iNOS、平均肺动脉压(mPAP)、肿瘤坏死因子(TNF-α)、白介素-6(IL-6)及基质金属蛋白酶-9(MMP-9)水平,并采用免疫组化方法对比三组大鼠BAX及Bcl-2表达。结果:大体观察显示,损伤组及干预组大鼠肺组织充血肿胀,呈现暗红色,干预组情况优于损伤组。对比显示,损伤组大鼠肺组织匀浆中mPAP、NO及iNOS水平明显高于干预组(P<0.05),干预组明显高于对照组(P<0.05);损伤组大鼠肺组织匀浆中TNF-α、IL-6及MMP-9水平明显高于干预组(P<0.05),干预组明显高于对照组(P<0.05);损伤组大鼠BAX表达高于干预组,干预组高于对照组(P<0.05);Bcl-2表达损伤组低于干预组,干预组组低于对照组(P<0.05)。结论:烟草烟雾诱导能够使大鼠肺组织NO及iNOS水平上升,应用iNOS抑制剂能够显著缓解烟草烟雾诱导的大鼠肺气肿及肺动脉高压症状,降低其炎症因子水平,其可能与上调凋亡蛋白Bcl-2表达、下调Bax蛋白表达有关。

Objective:To investigate the effect of inducible nitric oxide synthase(iNOS)inhibitors in alleviating tobacco smoke-induced emphysema and pulmonary hypertension in rats.Methods:60 healthy SD rats were randomly divided into three groups,the control group,the injury group and the intervention group,20 cases in each group.The control group was routinely reared,and the rats in the injury group were established with tobacco smoke injury model.The rats in the intervention group were injected with iNOS inhibitor after the model was established.Rat lung tissue was observed for its shape difference.Nitric oxide(NO)levels,iNOS levels,mean pulmonary artery pressure(mPAP),tumor necrosis factor(TNF-α)levels,interleukin-6(IL-6)levels,and matrix metalloproteinase-9(MMP-9)levels were compared in the lung tissue homogenates of the three groups.The immunohistochemical methods were used to compare BAX and Bcl-2 expression in three groups of mice.Results:Gross observation showed that the lung tissue of the rats was swollen and dark red in injury group and intervention group,and the intervention group was better than the injury group.The comparison showed that the levels of mPAP,NO and iNOS in the lung tissue homogenate of the injured group were significantly higher than those in the intervention group(P<0.05).The intervention group was significantly higher than the control group(P<0.05).The comparison showed that the levels of TNF-α,IL-6 and MMP-9 in the lung tissue homogenate of the injured group were significantly higher than those in the intervention group(P<0.05).The intervention group was significantly higher than the control group(P<0.05).The BAX expression in the injured group was higher than that in the intervention group,the intervention group was higher than that in the control group(P<0.05),and the Bcl-2 expression injury group was lower than the intervention group,and the intervention group was lower than that in the control group(P<0.05).Conclusion:Tobacco smoke induction can increase the levels of NO and iNOS in lung tissue of rats.The application of iNOS inhibitor can significantly alleviate the symptoms of pulmonary emphysema and pulmonary hypertension induced by tobacco smoke,and reduce the level of inflammatory factors,which may be related to the up-regulation of apoptosis protein Bcl-2 expression and the down-regulation of Bax protein expression.