养胃解毒合剂对脓毒症大鼠肠组织凋亡因子Bax、Bcl2和Caspase3的影响
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摘要
目的:通过观察养胃解毒合剂对脓毒症大鼠肠组织TNF-α的表达及Bax、Bcl2、Caspase3相关凋亡蛋白的影响,探讨养胃解毒合剂对脓毒症大鼠的肠保护机制。方法:140只大鼠分为7组,正常组20只、模型组20只、中药正常剂量组20只、中药高剂量(2倍)组20只、西药组(泰能)20只、西药+中药正常剂量组20只、西药+中药高剂量组20只。通过HE染色观察肠组织病理改变;ELISA法对TNF-α的表达进行检测;采用Western Blot(WB)法检测Bax、Bcl2、Caspase3蛋白表达。结果:与正常组比较,模型组TNF-α含量明显升高,Bax、Caspase3蛋白表达上调,Bcl2蛋白表达下调(P<0.01),西药+中药高剂量联合治疗后TNF-α表达明显减少(P<0.01)。西药+中药高剂量组肠组织Bax和Caspase3蛋白表达水平下调,Bcl-2蛋白表达水平上调(P<0.01)。结论:养胃解毒合剂可能通过抑制TNF-α的表达,介导调控肠组织的Bax、Bcl2、Caspase3凋亡蛋白,起到对脓毒症大鼠的肠保护作用。
Objective: To demonstrate the mechanism of Yangwei Jiedu Mixture in rescuing intestine of sepsis rats by investigating TNF-α,Bax,Bcl2 and Caspase3 protein expressions. Method: A total of 140 SD rats were randomly divided into 7 groups(20 rats in each) as following:control group,model group,Yangwei Jiedu Mixture regular dose group,Yangwei Jiedu Mixture high dose group,TIENAM group,Yangwei Jiedu Mixture regular dose plus TIENAM group and Yangwei Jiedu Mixture high dose plus TIENAM group. Histology was used to observe the pathogenic change in intestine tissue. ELISA was used to compare TNF-α expression in intestine. Western blotting was used to examine the protein expressions of Bax,Bcl2 and Caspase3. Result: Comparing to control group,model group showed higher protein expressions of TNF-α,Bax and Caspase3 and lower expression of Bcl2 significantly( P < 0. 01). And TNF-α,Bax and Caspase3 were significantly down-regulated( P < 0. 01) and Bcl-2 was dramatically up-regulated( P < 0. 01) in Yangwei Jiedu Mixture high dose plus TIENAM group. Conclusion: Yangwei Jiedu Mixture can protect intestine of sepsis rats by inhibiting TNF-α expression to regulate apoptosis-relevant protein Bax,Bcl2 and Caspase3.
Objective: To demonstrate the mechanism of Yangwei Jiedu Mixture in rescuing intestine of sepsis rats by investigating TNF-α,Bax,Bcl2 and Caspase3 protein expressions. Method: A total of 140 SD rats were randomly divided into 7 groups(20 rats in each) as following:control group,model group,Yangwei Jiedu Mixture regular dose group,Yangwei Jiedu Mixture high dose group,TIENAM group,Yangwei Jiedu Mixture regular dose plus TIENAM group and Yangwei Jiedu Mixture high dose plus TIENAM group. Histology was used to observe the pathogenic change in intestine tissue. ELISA was used to compare TNF-α expression in intestine. Western blotting was used to examine the protein expressions of Bax,Bcl2 and Caspase3. Result: Comparing to control group,model group showed higher protein expressions of TNF-α,Bax and Caspase3 and lower expression of Bcl2 significantly( P < 0. 01). And TNF-α,Bax and Caspase3 were significantly down-regulated( P < 0. 01) and Bcl-2 was dramatically up-regulated( P < 0. 01) in Yangwei Jiedu Mixture high dose plus TIENAM group. Conclusion: Yangwei Jiedu Mixture can protect intestine of sepsis rats by inhibiting TNF-α expression to regulate apoptosis-relevant protein Bax,Bcl2 and Caspase3.
引文
[1]Han H,Wang HL,Yu XZ,et al.Gastrointestinal dysfunction/failure and critical care medicine[J].Acta Acad Med Sin,2008,30(2):224-227.
[2]孙小平,邓扬嘉,李佳俊.PPARγ促进miR-16表达抑制脓毒症炎症反应的作用研究[J].第三军医大学学报,2017,8(75):1-7.
[3]孙红涛.氢气对重度脓毒症小鼠肠道屏障功能障碍的保护作用及机制研究[D].天津:天津医科大学,2016.
[4]潘卫红.中药敷脐护理技术对脓毒症伴胃肠功能障碍患者的疗效观察[J].四川中医,2014,32(12):166-168.
[5]Rittirsch D,Flierl M A,Ward P A.Harmful molecular mechanisms in sepsis[J].Nature reviews.Immunology,2008,8(10):776.
[6]Xavier R J,Podolsky D K.Unravelling the pathogenesis of inflammatory bowel disease[J].Nature,2007,448(7152):427.
[7]王磊,王立峰.乌司他丁抑制脓毒症大鼠肾脏细胞凋亡Caspase信号机制研究[J].临床急症杂志,2017,127(1):30-34.
[8]王立峰,王磊,陈俊杰.乌司他丁对脓毒症大鼠肠屏障保护抗凋亡机制研究[J].临床急诊杂志,2017,9(18):686-689.
[9]姚咏明,盛志勇.脓毒症防治学[M].北京科学技术文献出版社,2008:3.
[10]Harris-Benedict公式在老年严重脓毒症患者营养支持治疗中的指导价值[J].中国老年学杂志,2017,16(37):4051-4053.
[11]大黄灌肠+中药热敷联合西药治疗脓毒症随机平行对照研究[J].实用中医内科杂志,2017,4(31):29-32.
[12]参麦注射液对气阴两虚型脓毒症患者肠屏障功能的保护作用[J].中国药业,2017,22(26):34-36.
[13]王阳.养胃解毒合剂对脓毒症模型大鼠作用的实验研究[D].沈阳:辽宁中医药大学,2013.
[14]张馨元.“化癖扶正,通腑和胃”法治疗脓毒症的临床研究[D].沈阳:辽宁中医药大学,2014.
[15]Kouroumichakis I,Papanas N,Proikaki S,et al.Statins in prevention and treatment of severe sepsis and septic shock[J].Eur,J lntem Med,2011,22:125-133.
[16]Yin XM,Ding WX.Death receptor activation induced hepatocyte apoptosis and liver injury[J].Curr Mol Med,2003,3:491-508.
[17]PF Piguet,C Vesin,J Guo,et al.TNF-induced enterocyte apoptosis in mice is mediated by the TNF receptor 1 and does not require p53[J].European Journal of Immunology,1998,28(11):3499.
[18]Tsujimoto Y,Cossman J,Jalfe E,et al.Involvement of Bcl-2gene in human follicular lymphoma[J].Seience,1985,228(4706):1440-1443.
[19]Kuranaga E.Caspase signaling in animal development[J].Dev Growth Differ,2011,53(2):137-148.
[20]Daemen MA,Van't Veer C,Denecker G,et al.Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation[J].Clin Invest,1999,104(5):541-549.
[2]孙小平,邓扬嘉,李佳俊.PPARγ促进miR-16表达抑制脓毒症炎症反应的作用研究[J].第三军医大学学报,2017,8(75):1-7.
[3]孙红涛.氢气对重度脓毒症小鼠肠道屏障功能障碍的保护作用及机制研究[D].天津:天津医科大学,2016.
[4]潘卫红.中药敷脐护理技术对脓毒症伴胃肠功能障碍患者的疗效观察[J].四川中医,2014,32(12):166-168.
[5]Rittirsch D,Flierl M A,Ward P A.Harmful molecular mechanisms in sepsis[J].Nature reviews.Immunology,2008,8(10):776.
[6]Xavier R J,Podolsky D K.Unravelling the pathogenesis of inflammatory bowel disease[J].Nature,2007,448(7152):427.
[7]王磊,王立峰.乌司他丁抑制脓毒症大鼠肾脏细胞凋亡Caspase信号机制研究[J].临床急症杂志,2017,127(1):30-34.
[8]王立峰,王磊,陈俊杰.乌司他丁对脓毒症大鼠肠屏障保护抗凋亡机制研究[J].临床急诊杂志,2017,9(18):686-689.
[9]姚咏明,盛志勇.脓毒症防治学[M].北京科学技术文献出版社,2008:3.
[10]Harris-Benedict公式在老年严重脓毒症患者营养支持治疗中的指导价值[J].中国老年学杂志,2017,16(37):4051-4053.
[11]大黄灌肠+中药热敷联合西药治疗脓毒症随机平行对照研究[J].实用中医内科杂志,2017,4(31):29-32.
[12]参麦注射液对气阴两虚型脓毒症患者肠屏障功能的保护作用[J].中国药业,2017,22(26):34-36.
[13]王阳.养胃解毒合剂对脓毒症模型大鼠作用的实验研究[D].沈阳:辽宁中医药大学,2013.
[14]张馨元.“化癖扶正,通腑和胃”法治疗脓毒症的临床研究[D].沈阳:辽宁中医药大学,2014.
[15]Kouroumichakis I,Papanas N,Proikaki S,et al.Statins in prevention and treatment of severe sepsis and septic shock[J].Eur,J lntem Med,2011,22:125-133.
[16]Yin XM,Ding WX.Death receptor activation induced hepatocyte apoptosis and liver injury[J].Curr Mol Med,2003,3:491-508.
[17]PF Piguet,C Vesin,J Guo,et al.TNF-induced enterocyte apoptosis in mice is mediated by the TNF receptor 1 and does not require p53[J].European Journal of Immunology,1998,28(11):3499.
[18]Tsujimoto Y,Cossman J,Jalfe E,et al.Involvement of Bcl-2gene in human follicular lymphoma[J].Seience,1985,228(4706):1440-1443.
[19]Kuranaga E.Caspase signaling in animal development[J].Dev Growth Differ,2011,53(2):137-148.
[20]Daemen MA,Van't Veer C,Denecker G,et al.Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation[J].Clin Invest,1999,104(5):541-549.