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Cav-1和TNF-α在機(jī)械通氣聯(lián)合高氧致大鼠急性肺損傷中的表達(dá)研究

發(fā)布時(shí)間:2018-11-09 11:52
【摘要】:目的:觀察機(jī)械通氣聯(lián)合高氧對(duì)小窩蛋白-1(cavolin-1,cav-1)和腫瘤壞死因子α(TNF-α)表達(dá)的影響,探討機(jī)械通氣聯(lián)合高氧致大鼠急性肺損傷(acute lung injury,ALI)的發(fā)生機(jī)制。方法:雄性SD大鼠24只,隨機(jī)分為對(duì)照組、機(jī)械通氣組(MV組)和機(jī)械通氣聯(lián)合高氧組(MV+HO_2組)。觀察各組大鼠肺組織的病理學(xué)變化,測(cè)定肺濕/干重(W/D);采取BCA法測(cè)定BALF中蛋白的含量;采用免疫組化染色法和Western blot法測(cè)定肺組織中cav-1蛋白的表達(dá);采用RT-qPCR法測(cè)定肺組織中NF-κB mRNA和TNF-αmRNA表達(dá)。結(jié)果:與對(duì)照組相比,MV組和MV+HO_2組大鼠肺組織W/D比值、BALF中總蛋白含量以及肺組織中cav-1蛋白、NF-κB mRNA和TNF-αmRNA表達(dá)水平均顯著升高(均P0.001),同時(shí)肺組織呈明顯損傷性改變;MV組和MV+HO_2組之間上述指標(biāo)比較差異也均有統(tǒng)計(jì)學(xué)意義(均P0.001),但MV組肺組織病理?yè)p傷程度較MV+HO_2組輕。進(jìn)行相關(guān)性分析后顯示,各組大鼠肺組織cav-1蛋白的表達(dá)量與NF-κB mRNA表達(dá)量之間呈正相關(guān)(r=0.827,P0.001);NF-кB mRNA表達(dá)量與TNF-αmRNA表達(dá)量之間也呈正相關(guān)(r=0.903,P0.001)。結(jié)論:機(jī)械通氣和高氧均可誘發(fā)和加重肺組織損傷,二者具有相互協(xié)同、相互促進(jìn)作用,其發(fā)生機(jī)制可能與肺組織cav-1表達(dá)上調(diào)有關(guān)。cav-1可能通過(guò)激活NF-κB調(diào)控多種前炎細(xì)胞因子,如TNF-α、IL-1、IL-8等表達(dá)和釋放,從而形成“瀑布式級(jí)聯(lián)放大效應(yīng)”,最終導(dǎo)致肺組織炎癥性損傷。
[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 偽 (TNF- 偽) 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- 偽 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- 偽 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- 偽 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- 偽, 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.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R563.8

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