Cav-1和TNF-α在机械通气联合高氧致大鼠急性肺损伤中的表达研究

发布时间：2018-11-09 11:52

【摘要】：目的:观察机械通气联合高氧对小窝蛋白-1(cavolin-1,cav-1)和肿瘤坏死因子α(TNF-α)表达的影响,探讨机械通气联合高氧致大鼠急性肺损伤(acute lung injury,ALI)的发生机制。方法:雄性SD大鼠24只,随机分为对照组、机械通气组(MV组)和机械通气联合高氧组(MV+HO_2组)。观察各组大鼠肺组织的病理学变化,测定肺湿/干重(W/D);采取BCA法测定BALF中蛋白的含量;采用免疫组化染色法和Western blot法测定肺组织中cav-1蛋白的表达;采用RT-qPCR法测定肺组织中NF-κB mRNA和TNF-αmRNA表达。结果:与对照组相比,MV组和MV+HO_2组大鼠肺组织W/D比值、BALF中总蛋白含量以及肺组织中cav-1蛋白、NF-κB mRNA和TNF-αmRNA表达水平均显著升高(均P0.001),同时肺组织呈明显损伤性改变;MV组和MV+HO_2组之间上述指标比较差异也均有统计学意义(均P0.001),但MV组肺组织病理损伤程度较MV+HO_2组轻。进行相关性分析后显示,各组大鼠肺组织cav-1蛋白的表达量与NF-κB mRNA表达量之间呈正相关(r=0.827,P0.001);NF-кB mRNA表达量与TNF-αmRNA表达量之间也呈正相关(r=0.903,P0.001)。结论:机械通气和高氧均可诱发和加重肺组织损伤,二者具有相互协同、相互促进作用,其发生机制可能与肺组织cav-1表达上调有关。cav-1可能通过激活NF-κB调控多种前炎细胞因子,如TNF-α、IL-1、IL-8等表达和释放,从而形成“瀑布式级联放大效应”,最终导致肺组织炎症性损伤。
[Abstract]:Objective: to observe the effect of mechanical ventilation combined with hyperoxia on the expression of fossa protein-1 (cavolin-1,cav-1) and tumor necrosis factor 伪 (TNF- 伪) in rats with acute lung injury induced by mechanical ventilation and hyperoxia. ALI). Methods: Twenty-four male SD rats were randomly divided into control group, mechanical ventilation group (MV group) and mechanical ventilation combined with hyperoxia group (MV HO_2 group). Lung wet / dry weight (W / D), protein content in BALF and expression of cav-1 protein in lung tissue were determined by BCA method and Western blot method, respectively. The expression of NF- 魏 B mRNA and TNF- 伪 mRNA in lung tissue was determined by RT-qPCR method. Results: compared with control group, the ratio of W / D in lung tissue, the content of total protein in BALF, the expression of cav-1 protein, NF- 魏 B mRNA and TNF- 伪 mRNA in lung tissue in MV group and MV HO_2 group were significantly higher than those in control group (P0.001). At the same time, the lung tissue was obviously damaged. The difference of the above indexes between MV group and MV HO_2 group was statistically significant (P0.001), but the degree of lung pathological injury in MV group was less than that in MV HO_2 group. The correlation analysis showed that there was a positive correlation between the expression of cav-1 protein and the expression of NF- 魏 B mRNA in lung tissue of rats in each group (r = 0.827, P 0.001). There was also a positive correlation between the expression of NF- B mRNA and the expression of TNF- 伪 mRNA (r = 0.903, P 0.001). Conclusion: mechanical ventilation and hyperoxia can induce and aggravate lung injury. The mechanism may be related to the up-regulation of cav-1 expression in lung tissue. Cav-1 may regulate the expression and release of many proinflammatory cytokines, such as TNF- 伪, IL-1,IL-8 and so on, by activating NF- 魏 B. Thus forming a cascade of cascade amplification effect, resulting in inflammatory lung tissue damage.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.8

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