参麦注射液对肠缺血/再灌注肺损伤大鼠肺组织p38MAPK及凋亡相关基因表达的影响
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摘要
目的:观察参麦注射液(SM)对肠缺血/再灌注(I/R)肺损伤大鼠肺组织p38MAPK和凋亡相关基因Bax、Bcl-2蛋白表达的影响,探讨其保护机制。方法:采用夹闭肠系膜上动脉(SMA)方法建立大鼠肠I/R损伤模型。24只SD大鼠随机分为对照组(Control组)、肠缺血/再灌注组(I/R组)、参麦注射液组(SM+I/R组),每组8只。比较各组大鼠肺湿/干比(W/D)、肺表面活性物质主要成分卵磷脂(PC)及总磷脂(TPL)含量的变化;同时免疫组织化学法检测各组大鼠肺组织中p38MAPK、Bax及Bcl-2蛋白的表达水平。结果:与对照组比较,I/R组肺组织W/D明显升高,而PC和TPL的含量显著降低,肺组织p38MAPK、Bcl-2和Bax蛋白表达明显增强(P均<0.01),其中Bax的增强比Bcl-2的增强更为明显,Bcl-2/Bax比值降低(P<0.01);与I/R组比较,SM+I/R组大鼠肺组织W/D明显降低,PC和TPL的含量增加,肺组织p38MAPK和Bax蛋白表达下降(P均<0.01),Bcl-2的表达增强,Bcl-2/Bax比值明显升高(P<0.01)。相关分析显示,肠I/R时肺组织p38MAPK蛋白表达水平与肺表面活性物质主要功能成分PC含量及凋亡基因Bcl-2/Bax比值呈负相关(r分别为-0.787,-0.731,P均<0.01)。结论:SM可能通过抑制p38MAPK信号通路的激活,提高Bcl-2/Bax比值来阻抑细胞凋亡,从而减轻肠I/R时的肺损伤。
Objective: To observe the effects of Shenmai injection( SM) on p38 MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion( I/R) in rats and to investigate the protective mechanism of SM. Methods: Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery( SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group,intestinal ischemia/reperfusion group( I/R group),Shenmai injection treated group( SM+I/R group). Lung wet/dry weight ratio( W/D),the contents of phosphatidylcholine( PC) and total phospholipid( TPL) which are the major ingredients of pulmonary surfactant were measured,as well as the expression levels of p38 MAPK,Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method. Results: Compared with control group,lung W/D was significantly increased,the contents of PC and TPL were significantly decreased,the protein expression levels of p38 MAPK,Bcl-2 and Bax were significantly increased in I/R group( all P<0.01).But Bax protein expression was much greater than Bcl-2 protein expression,the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group( P<0.01). Compared with I/R group,lung W/D was significantly decreased,while the contents of PC and TPL were significantly increased,the p38 MAPK and Bax protein expression levels were significantly decreased in SM + I/R group( all P<0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group( P<0.01). The correlation analysis indicated that the expression level of p38 MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax( r is-0.787 and-0.731,all P<0.01). Conclusion: SM can protect the lung injury induced by intestinal I/R injury,which may be mediated by inhibiting the activation of p38 MAPK,improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.
Objective: To observe the effects of Shenmai injection( SM) on p38 MAPK and the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion( I/R) in rats and to investigate the protective mechanism of SM. Methods: Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery( SMA) for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: control group,intestinal ischemia/reperfusion group( I/R group),Shenmai injection treated group( SM+I/R group). Lung wet/dry weight ratio( W/D),the contents of phosphatidylcholine( PC) and total phospholipid( TPL) which are the major ingredients of pulmonary surfactant were measured,as well as the expression levels of p38 MAPK,Bcl-2 and Bax proteins in lung tissue were examined by using immunohistochemical method. Results: Compared with control group,lung W/D was significantly increased,the contents of PC and TPL were significantly decreased,the protein expression levels of p38 MAPK,Bcl-2 and Bax were significantly increased in I/R group( all P<0.01).But Bax protein expression was much greater than Bcl-2 protein expression,the ratio of Bcl-2 to Bax were significantly decreased in I/R group than that in control group( P<0.01). Compared with I/R group,lung W/D was significantly decreased,while the contents of PC and TPL were significantly increased,the p38 MAPK and Bax protein expression levels were significantly decreased in SM + I/R group( all P<0.01); both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SM+I/R group than those in I/R group( P<0.01). The correlation analysis indicated that the expression level of p38 MAPK protein in lung tissue was negatively correlated with the contents of PC and the ratio of Bcl-2 to Bax( r is-0.787 and-0.731,all P<0.01). Conclusion: SM can protect the lung injury induced by intestinal I/R injury,which may be mediated by inhibiting the activation of p38 MAPK,improving the ratio of Bcl-2 to Bax to inhibit lung apoptosis.
引文
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[14]Ye LF,Zheng YR,Wang LH.Effects of Shenmai injection and its bioactive components following ischemia/reperfusion in cardiomyocytes[J].Exp Ther Med,2015,10(4):1348-1354.
[15]于齐宏,杜奕奇,李兆申,等.参麦注射液减轻大鼠重症急性胰腺炎相关性肺损伤[J].第二军医大学学报,2013,34(11):1183-1186.
[16]刘小芳.参麦注射液治疗急性肺损伤的疗效及对血清ICAM-1、ET-1及NO的影响[J].现代中西医结合杂志,2017,26(25):2784-2786.
[17]王艳蕾,景友玲,赵景霞,等.参麦注射液对肢体缺血/再灌注时肺脂质过氧化损伤的防护作用[J].中国应用生理学杂志,2006,22(1):13-15.
[2]Onder A,Kapan M,Gümüs M,et al.The protective effects of curcumin on intestine and remote organs against mesenteric ischemia/reperfusion injury[J].Turk J Gastroenterol,2012,23(2):141-147.
[3]Tan H,Chen L,Ma J.Penehyclidine hydrochloride postconditioning reduces ischemia/reperfusion-induced cardiomyocyte apoptosis in rats[J].Exp Ther Med,2017,14(5):4272-4278.
[4]Yu Y,Liu Q,Guo S,et al.2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl-2 pathway[J].J Cell Mol Med,2017,21(12):3540-3551.
[5]黄林静,张聪聪,赵美平,等.MAPK信号通路对大鼠低氧性PASMCs增殖、凋亡的调控[J].中国应用生理学杂志,2017,33(3):226-230.
[6]王艳蕾,崔国金,蔡庆艳,等.参麦注射液对肠缺血再灌注肺脂质过氧化损伤的影响[J].天津医药,2010,38(11):986-989.
[7]高晓明,宋建良,谢翠微,等.心钠素与实验性肺水肿[J].北京医科大学学报,1987,19(2):69-71.
[8]李影林.中华医学检验全书[M].北京:人民卫生出版社,1996:737-739.
[9]Zhao L,Gu Q,Xiang L,et al.Curcumin inhibits apoptosis by modulating Bax/Bcl-2 expression and alleviates oxidative stress in testes of streptozotocin-induced diabetic rats[J].Ther Clin Risk Manag,2017,13:1099-1105.
[10]Cao S,Zhu X,Du L.P38 MAP kinase is involved in oleuropein-induced apoptosis in A549 cells by a mitochondrial apoptotic cascade[J].Biomed Pharmacother,2017,95:1425-1435.
[11]Zhao HG,Zhou SL,Lin YY,et al.Toxicarioside N induces apoptosis in human gastric cancer SGC-7901 cell by activating the p38MAPK pathway[J].Arch Pharm Res,2018,41(1):71-78.
[12]Cuenda A,Rousseau S.p38 MAP-kinases pathway regulation,function and role in human diseases[J].Biochim Biophys Acta,2007,1773(8):1358-1375.
[13]Corre I,Paris F,Huot J.The p38 pathway,a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells[J].Oncotarget,2017,8(33):55684-55714.
[14]Ye LF,Zheng YR,Wang LH.Effects of Shenmai injection and its bioactive components following ischemia/reperfusion in cardiomyocytes[J].Exp Ther Med,2015,10(4):1348-1354.
[15]于齐宏,杜奕奇,李兆申,等.参麦注射液减轻大鼠重症急性胰腺炎相关性肺损伤[J].第二军医大学学报,2013,34(11):1183-1186.
[16]刘小芳.参麦注射液治疗急性肺损伤的疗效及对血清ICAM-1、ET-1及NO的影响[J].现代中西医结合杂志,2017,26(25):2784-2786.
[17]王艳蕾,景友玲,赵景霞,等.参麦注射液对肢体缺血/再灌注时肺脂质过氧化损伤的防护作用[J].中国应用生理学杂志,2006,22(1):13-15.
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