不同剂量秋水仙碱对烟草烟雾引起的血管内皮炎性微环境改变的影响

Effects of colchicine at different doses on inflammatory changes, oxidative stress and endothelial dysfunction induced by tobacco smoke

目的目前关于秋水仙碱对血管内皮炎性微环境改变影响的研究较少。文中旨在观察不同剂量秋水仙碱干预对经烟草烟雾刺激所引起的大鼠主动脉炎性变化、氧化应激和内皮功能不全的影响。方法将40只SD大鼠随机分为:对照组(吸入空气+蒸馏水)、烟雾组(吸入烟雾+管饲蒸馏水)、烟雾+低剂量秋水仙碱组(吸入烟雾+0.1 mg/(kg·d)秋水仙碱)、烟雾+中剂量秋水仙碱组(吸入烟雾+0.5 mg/(kg·d)秋水仙碱)、烟雾+高剂量秋水仙碱组(吸入烟雾+1.0 mg/(kg·d)秋水仙碱),每组8只。测量细胞黏附分子(ICAM-1),单核细胞趋化蛋白-1(MCP-1)、血管间黏附分子(VCAM-1)、IL-1β、IL-6、肿瘤坏死因子а(TNFa)的mRNA、超氧化歧化酶(SOD)活力,一氧化氮(NO)、丙二醛(MDA)和一氧化氮合成酶(eNOs)含量,并测试其主动脉的舒张能力。结果与对照组相比,其他各组IL-6、MCP-1、ICAM、VCAM、TNFa以及IL-1β炎性因子表达明显升高(P<0.05)。烟雾+低剂量秋水仙碱组、烟雾+中剂量秋水仙碱组、烟雾+高剂量秋水仙碱组炎性因子表达低于烟雾组(P<0.05)。与对照组相比,烟雾组大鼠胸主动脉环对乙酰胆碱(Ach)诱导的内皮依赖性舒张幅度明显下降(P<0.05);给予不同剂量的秋水仙碱干预8周后,舒张下降幅度减小(P<0.05)。与对照组比较,其他各组大鼠主动脉MDA含量明显高于对照组(P<0.05)。烟雾+低剂量秋水仙碱组、烟雾+中剂量秋水仙碱组、烟雾+高剂量秋水仙碱组SOD活力、NO含量升高,MDA含量降低(P<0.05)。与其他组比较,烟雾组大鼠主动脉eNOs蛋白表达最低(P<0.05);与烟雾组比较,烟雾+低剂量秋水仙碱组、烟雾+中剂量秋水仙碱组、烟雾+高剂量秋水仙碱组eNOs表达增加(P<0.05)。结论烟草烟雾暴露可导致的动脉血管内皮炎性改变和诱发氧化应激,以及内皮功能不全;秋水仙碱干预可部分缓解这种异常变化,但其对主动脉内皮的改善效应未体现出剂量依赖性的变化。

Objective At present,there are few studies on the effect of colchicine on the changes of vascular endothelial micro-environment.The aim of this paper was to observe the effects of colchicine on the inflammatory changes of aorta,oxidative stress and endothelial dysfunction in rats stimulated by tobacco smoke.Methods Forty SD rats were randomly divided into control group(inhaled air+distilled water),smoke group(inhaled smoke+tube fed distilled water),smoke+low-dose colchicine group(inhaled smoke+0.1 mg/(kg·d)colchicine),smoke+medium-dose colchicine group(inhaled smoke+0.5 mg/(kg·d)colchicine),smoke+high-dose colchicine group(smoke inhalation+1.0 mg/(kg·d)colchicine),8 mice in each group.The mRNA and superoxide dismutase(SOD)activity of cell adhesion molecule 1(ICAM1),monocyte chemoattractant protein 1(MCP1),intervascular adhesion molecule 1(VCAM1),IL1β,IL6,tumor necrosis factor(TNFa)were measured.The contents of nitric oxide(NO),malondialdehyde(MDA)and nitric oxide synthase(eNOs),and the diastolic capacity of the aorta were tested.Results Compared with the control group,the expressions of IL6,MCP1,ICAM,VCAM,TNFa and IL1βinflammatory factors in other groups were significantly increased(P<0.05).The expression of inflammatory factors in smoke+low-dose colchicine group,smoke+medium-dose colchicine group and smoke+high-dose colchicine group was lower than that in smoke group(P<0.05).Compared with the control group,the endothelium dependent relaxation amplitude induced by Ach in thoracic aorta ring of rats in smoke group was significantly decreased(P<0.05).After 8 weeks of different doses of colchicine,the diastolic decline decreased(P<0.05).Compared with control group,the content of MDA in aorta of other groups was significantly higher than that of control group(P<0.05).SOD activity and NO content were increased and MDA content was decreased in smoke+low dose colchicine group,smoke+medium dose colchicine group and smoke+high dose colchicine group(P<0.05).Compared with other groups,the expression of eNOs protein in aorta of rats in smoke group was the lowest(P<0.05).Compared with the smoke group,the expression of eNOs in the smoke+low-dose colchicine group,the smoke+medium-dose colchicine group and the smoke+high-dose colchicine group was increased(P<0.05).Conclusion Tobacco smoke exposure can cause inflammatory changes in arterial endothelium and induce oxidative stress,as well as endothelial dysfunction.Colchicine intervention could partially alleviate the abnormal changes,but its improvement effect on aortic endothelium did not show a dose-dependent change.