雷帕霉素对脂多糖诱导急性肺损伤的保护作用及可能机制研究

Protective effect of rapamycin on lipopolysaccharide induced acute lung injury and its possible mechanism

目的探讨雷帕霉素对脂多糖(LPS)诱导急性肺损伤的保护作用及可能机制。方法将90只大鼠随机分为对照组、LPS组和雷帕霉素处理组。HE染色观察肺组织病理学改变。酶联免疫吸附方法检测血清IL-6、IL-10和TNF-α的表达。硫代巴比妥酸方法、黄嘌呤氧化酶方法和酶促反应谷胱甘肽消耗方法分别测定血清MDA、SOD和GSH-Px活力。实时荧光定量PCR方法检测肺组织mTOR和P70S6K mRNA表达变化。结果雷帕霉素处理能降低LPS诱导的大鼠血清IL-6和TNF-α浓度,升高IL-10浓度;降低大鼠血清MDA含量,增加血清SOD和GSH-Px含量。此外,雷帕霉素明显降低IPS导致的大鼠肺组织mTOR和p70S6K mRNA表达升高。结论雷帕霉素可能通过抑制mTOR和p70S6K的表达,减轻炎症因子和氧化应激损伤,从而对LPS诱导的急性肺损伤发挥保护作用。

Objective To elucidate the protective effect of rapamycin on lipopolysaccharide(LPS) induced acute lung injury and its possible mechanism. Methods 90 rats were randomly divided into control group, LPS group and rapamycin treated group. HE staining was used to observe the pathological changes of lung tissue. The expression of IL-6, IL-10 and TNF-α in serum was detected by ELISA. The activities of MDA, SOD and GSH PX in serum were determined by thiobarbituric acid method, xanthine oxidase method and enzymatic glutathione consumption method. The expression of mTOR and P70 S6 K mRNA was detected by Real-time PCR. Results Rapamycin treatment significantly decreased the concentration of IL-6 and TNF-α, and increased the concentration of IL-10. Meanwhile, rapamycin treatment also significantly reduced the content of MDA in serum, and increased the content of SOD and GSH PX in serum. Moreover, rapamycin significantly reduced the increased expression of mTOR and P70 S6 K mRNA induced by LPS. Conclusion Rapamycin may play a protective role in LPS-induced acute lung injury by inhibiting the expression of mTOR and P70 S6 K, reducing inflammatory factors and oxidative stress injury.