李艳君,郭瑞敏,孙燕妮

• 1:上海中医药大学附属普陀医院

摘要(Abstract)：

肠屏障功能障碍是脓毒症发生发展的重要原因,由肠上皮细胞和细胞旁紧密连接结构组成的肠机械屏障是发挥肠屏障功能的主要成员。当其完整性遭到破坏,将引起无法控制的全身炎症反应,病死率较高,是急危重症需要攻克的难题之一。中药单体大黄素是大黄最重要的活性成分,在改善脓毒症肠屏障损伤方面取得了一系列成果。本文旨在整体上从脓毒症肠机械屏障结构的主要变化特点及分子生物学角度来深入阐述大黄素改善脓毒症肠机械屏障损伤的作用机制,以期为大黄素作用于脓毒症肠屏障功能障碍性疾病的科学研究提供理论基础。

关键词(KeyWords)： 脓毒症;肠机械屏障;大黄素;肠上皮细胞;紧密连接

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(81573901)

作者(Author): 李艳君,郭瑞敏,孙燕妮

参考文献(References)：

• [1]中华医学会重症医学分会.中国严重脓毒症/脓毒性休克治疗指南(2014)[J].中华内科杂志,2015,54(6):557-581.
• [2]Li Z,Gao M,Yang B,et al.Naringin attenuates MLC phosphorylation and NF-kappaB activation to protect sepsis-induced intestinal injury via RhoA/ROCK pathway[J].Biomed Pharmacother,2018,103:50-58.
• [3]Reintam Blaser A,Malbrain ML,Starkopf J,et al.Gastrointestinal function in intensive care patients:terminology,definitions and management.Recommendations of the ESICMWorking Group on Abdominal Problems[J].Intensive Care Med,2012,38(3):384-394.
• [4]刘宁,苏立杰,许树长,等.脓毒症合并急性胃肠损伤的危险因素与预后调查分析[J].同济大学学报:医学版,2015,36(2):53-58.
• [5]廖吕钊,江荣林.丹参酮改善脓毒症肠屏障功能的研究进展[J].浙江中医药大学学报,2017,41(2):171-174.
• [6]李闪闪,江荣林.中西医结合防治脓毒症胃肠功能障碍研究进展[J].浙江中西医结合杂志,2015,25(7):705-710.
• [7]王慧慧.脓毒症胃肠功能障碍中医用药规律探讨[D].济南:山东中医药大学,2015.
• [8]白小武,嵇武,丁博文,等.大黄素对肠黏膜屏障损伤的保护作用及机制研究[J].东南国防医药,2012,14(1):12-15.
• [9]Okumura R,Takeda K.Maintenance of intestinal homeostasis by mucosal barriers[J].Inflamm Regen,2018,38:5.
• [10]Gu GS,Ren JA,Li GW,et al.Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model:a pilot study[J].Int JClin Exp Med,2015,8(5):7333-7341.
• [11]Wang L,Cui YL,Zhang Z,et al.Rhubarb monomers protect intestinal mucosal barrier in sepsis via junction proteins[J].Chin Med J(Engl),2017,130(10):1218-1225.
• [12]金水芳,江荣林,雷澍.黄芪注射液对脓毒症大鼠肠道黏膜上皮细胞的保护作用及其机制研究[J].浙江中医药大学学报,2015,39(6):482-486.
• [13]Perrone EE,Jung E,Breed E,et al.Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis[J].Shock,2012,38(1):68-75.
• [14]李红梅,邢云,唐翔诩,等.小檗碱抑制脓毒症诱导的肠上皮细胞凋亡[J].中国病理生理杂志,2016,32(9):1660-1665.
• [15]Zhu W,Lu Q,Chen HW,et al.Protective effect of sodium tanshinoneⅡA sulfonate on injury of small intestine in rats with sepsis and its mechanism[J].Chin J Integr Med,2012,18(7):496-501.
• [16]Wu W,Wang S,Liu Q,et al.Metformin protects against LPS-induced intestinal barrier dysfunction by activating AMPKpathway[J].Mol Pharm,2018,15(8):3272-3284.
• [17]Lorentz CA,Liang Z,Meng M,et al.Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis[J].Mol Med,2017,23(1):155-165.
• [18]Al-Sadi R,Khatib K,Guo S,et al.Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier[J].Am J Physiol Gastrointest Liver Physiol,2011,300(6):1054-1064.
• [19]Ye D,Guo S,Al-Sadi R,et al.MicroRNA regulation of intestinal epithelial tight junction permeability[J].Gastroenterology,2011,141(4):1323-1333.
• [20]Xiao M,Zhu T,Zhang W,et al.Emodin ameliorates LPS-induced acute lung injury,involving the inactivation of NF-κBin mice[J].International Journal of Molecular Sciences,2014,15(11):19355-19368.
• [21]Zhang Y,Li J.Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by downregulating NF-kappabeta and myosin light-chain kinase pathways[J].Biochem Biophys Res Commun,2012,428(2):321-326.
• [22]Ye D,Ma I,Ma TY.Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier[J].Am J Physiol Gastrointest Liver Physiol,2006,290(3):496-504.
• [23]孙俊波,赵璐,史素琴,等.青蒿素减轻LPS诱导的肠上皮细胞屏障功能损伤的实验研究[J].中国病理生理杂志,2016,32(7):1285-1290.
• [24]Nighot M,Al-Sadi R,Guo S,et al.Lipopolysaccharide-induced increase in intestinal epithelial tight permeability is mediated by toll-like receptor 4/myeloid differentiation primary response 88(My D88)activation of myosin light chain kinase expression[J].Am J Pathol,2017,187(12):2698-2710.
• [25]王虑.大黄单体对脓毒症大鼠肠黏膜上皮细胞凋亡和增殖的影响[A].中华医学会、中华医学会急诊医学分会.中华医学会急诊医学分会第17次全国急诊医学学术年会论文集[C].中华医学会、中华医学会急诊医学分会,2014:2.
• [26]Chen YK,Xu YK,Zhang H,et al.Emodin alleviates jejunum injury in rats with sepsis by inhibiting in flammation response[J].Biomed Pharmacother,2016,84:1001-1007.
• [27]Wu W,Jiang RL,Wang LC,et al.Effect of Shenfu injection on intestinal mucosal barrier in a rat model of sepsis[J].Am J E-merg Med,2015,33(9):1237-1243.
• [28]Yin JT,Wan B,Liu DD,et al.Emodin alleviates lung injury in rats with sepsis[J].J Surg Res,2016,202(2):308-314.
• [29]许先锋.大黄素对肠上皮细胞炎症模型Caspase-3表达的影响[J].中国现代医药杂志,2012,14(11):47-48.
• [30]Lei Q.,Qiang F,Chao D,et al.Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-kappaB and HIF-1alpha signaling pathways[J].Int J Mol Med,2014,34(6):1629-1639.
• [31]Zhang S,Zheng S,Wang X,et al.Carbon monoxide-releasing molecule-2 reduces intestinal epithelial tight-junction damage and mortality in septic rats[J].Plos One,2015,10(12):e0145988.
• [32]Wang L,Cui YL,Zhang Z,et al.Rhubarb monomers protect intestinal mucosal barrier in sepsis via junction proteins[J].Chin Med J(Engl),2017,130(10):1218-1225.
• [33]Li A,Dong L,Duan ML,et al.Emodin improves lipopolysaccharide-induced microcirculatory disturbance in rat mesentery[J].Microcirculation,2013,20(7):617-628.
• [34]龚小军,郜朝霞,王传明.大黄素对急性胰腺炎大鼠相关炎性因子表达的影响[J].药物分析杂志,2015,35(12):2095-2098.
• [35]韦志军,吴先平,甘小亮,等.大黄素对小鼠缺血再灌注肠黏膜肥大细胞活性的影响[J].中国实验方剂学杂志,2011,17(16):167-170.