雷帕霉素在脓毒症致肺纤维化大鼠中应用研究  

Application of rapamycin in rats with sepsis induced pulmonary fibrosis

作　　者：陈硕 邵美琪 陈达[2] CHEN Shuo;SHAO Mei-qi;CHEN Da(Department of Emergency,The Fourth Affiliated Hospital of China Medical University,Shenyang 110032,China)

机构地区：[1]中国医科大学附属第四医院急诊科,辽宁沈阳110032 [2]中国医科大学附属第四医院全科医学科,辽宁沈阳110032

出　　处：《创伤与急危重病医学》2021年第3期180-185,共6页Trauma and Critical Care Medicine

基　　金：辽宁省自然科学基金(20180550035)。

摘　　要：目的探讨雷帕霉素在脓毒症致肺纤维化大鼠中的应用效果及其可能作用机制。方法选取90只SD大鼠,采用随机数字表法将其分为对照组、脓毒症组与雷帕霉素组,每组各30只。对照组大鼠给予生理盐水腹腔注射;脓毒症组大鼠给予脂多糖(LPS)腹腔注射;雷帕霉素组大鼠给予LPS、雷帕霉素腹腔注射。采用Ashcrof评分评估大鼠肺纤维化程度;分光光度法测定大鼠肺组织羟脯氨酸(HYP)含量;应用免疫印迹法检测α-平滑肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)表达;实时定量聚合酶链式反应检测大鼠肺组织基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶组织抑制物-1(TIMP-1)的表达。结果实验第7、14、21、28、35天,脓毒症组、雷帕霉素组大鼠肺组织Ashcrof评分,HYP含量,α-SMA、TGF-β1表达水平,MMP-2、TIMP-1的mRNA表达水平均明显高于对照组;雷帕霉素组大鼠肺组织Ashcrof评分,HYP含量,α-SMA、TGF-β1表达水平,MMP-2、TIMP-1的mRNA表达水平均明显低于脓毒症组,差异有统计学意义(P<0.05)。结论雷帕霉素可能通过降低TGF-β1、α-SMA、MMP-2及TIMP-1的表达,减轻脓毒症致肺纤维化的进展程度,从而发挥对肺损伤的保护作用。Objective To investigate the effect and possible mechanism of rapamycin in rats with sepsis induced pulmonary fibrosis.Methods Ninety SD rats were randomly divided into control group,sepsis group and rapamycin group,with 30 rats in each group.The rats in control group were intraperitoneally injected with normal saline;rats in sepsis group were intraperitoneally injected with lipopolysaccharide(LPS);rats in rapamycin group were intraperitoneally injected with LPS and rapamycin.Ashcrof score was used to evaluate the degree of pulmonary fibrosis in rats.Hydroxyproline(HYP)content in rat lung tissue was determined by spectrophotometry.The expression ofα-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)were detected by western blot assay.The expression of matrix metalloproteinase-2(MMP-2)and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)in rat lung tissues were detected by real-time quantitative polymerase chain reaction.Results On day 7,14,21,28 and 35 of the experiment,Ashcrof score,HYP content,the expression ofα-SMA and TGF-β1,mRNA expression of MMP-2 and TIMP-1 were significantly higher in sepsis group and rapamycin group than those in control group;ashcrof score,HYP content,the expression ofα-SMA and TGF-β1,mRNA expression of MMP-2 and TIMP-1 in rapamycin group were significantly lower than those in sepsis group,with statistically significant differences(P<0.05).Conclusion Rapamycin may reduce the progression of pulmonary fibrosis induced by sepsis by decreasing the expression of TGF-β1,α-SMA,MMP-2 and TIMP-1,thus play a protective role in lung injury.

关 键 词：脓毒症 肺纤维化 雷帕霉素 基质金属蛋白酶-2 基质金属蛋白酶组织抑制物-1 

分 类 号：R459.7[医药卫生—急诊医学]