健脾利湿养肝方对慢加急性肝衰竭模型嘌呤能离子通道型受体7影响的实验研究
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摘要
目的观察中药健脾利湿养肝方对慢加急性肝衰竭(ACLF)模型大鼠嘌呤能离子通道型受体7(P2X7R)的影响,探讨健脾养肝利湿方治疗ACLF的作用机制。方法利用免疫法建立ACLF模型,随机分为模型组和实验组,模型组给予生理盐水灌胃,实验组给予健脾利湿养肝方灌胃,治疗1周。10%水合氯醛麻醉腹主动脉取血处死,留取肝脏标本行HE、免疫组化、Western blot、RT-PCR检测。结果实验组较对照组可以降低ACLF模型大鼠谷丙转氨酶(ALT)、谷草转氨酶(AST)、凝血酶原时间(PT)、国际标准比值(INR),提高凝血酶原活动度(PTA),差异具有统计学意义(<0.05);Western blot结果显示,实验组较对照P2X7R蛋白在肝内的表达降低,差异具有统计学意义(<0.05);RT-PCR显示,实验组较对照组P2X7R基因表达降低,差异具有统计学意义(<0.05)。结论中药健脾利湿养肝方可以降低ACLF模型大鼠P2X7R的表达。
引文
[1]Jalan R,Moreau R,Kamath P S,et al.Acute-on-Chronic Liver Failure:A Distinct Clinical Condition[J].Semin Liver Dis,2016,36(2):107-108.
[2]Richard M,Pajiv J,Pere G,et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J].Gastroenterology,2013,144(7):1426-1437.
[3]Garg H,Kumar A,Garg V,et al.Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure[J].Dig Liver Dis,2012,44(2):166-171.
[4]Jalan R,Gines P,Olson JC,et al.Acute-on chronic liver failure[J].J Hepatol,2012,57(6):1336-1348.
[5]叶一农,高志良.乙型肝炎肝衰竭发生机制中的三重打击[J].传染病信息,2009(5):276-279.
[6]Ousingsawat J,Cabrita I,Wanitchakool P,et al.Ca2+signals,cell membrane disintegration,and activation of TMEM16F during necroptosis[J].Cell Mol Life Sci,2017,74(1):173-181.
[7]Shieh CH,Heinrich A,Serchov T,et al.P2X7-dependent,but differentially regulated release of IL-6,CCL2,and TNFalpha in cultured mouse microglia[J].Glia,2014,62(4):592-607.
[8]Picollo A,Malvezzi M,Accardi A.TMEM16 proteins:unknown structure and confusing functions[J].J Mol Biol,2015,427(1):94-105.
[9]Gicquel T,Le DaréB,Boichot E,et al.Purinergic receptors:new targets for the treatment of gout and fibrosis[J].Fundamental&Clinical Pharmacology,2017,31(2):136-146.
[10]Souza VDCG,Dos Santos JT,Cabral FL,et al.Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease[J].Microbial Pathogenesis,2017(104):32-38.
[11]王丽雁,蔡文琴,陈鹏慧.P2X7受体在OPCs缺氧缺血性损伤中作用的初步研究[J].重庆医学,2010,39(21):2895-2897.
[12]Wanke D,Mauch-Mücke K,Holler E,et al.Human betadefensin-2 and-3 enhance pro-inflammatory cytokine expression induced by TLR ligands via ATP-release in a P2X7R dependent manner[J].Immunobiology,2016,221(11):1259-1265.
[13]Park JH,Williams DR,Lee JH,et al.Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion[J].J Med Chem,2016,59(16):7410-7430.
[2]Richard M,Pajiv J,Pere G,et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J].Gastroenterology,2013,144(7):1426-1437.
[3]Garg H,Kumar A,Garg V,et al.Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure[J].Dig Liver Dis,2012,44(2):166-171.
[4]Jalan R,Gines P,Olson JC,et al.Acute-on chronic liver failure[J].J Hepatol,2012,57(6):1336-1348.
[5]叶一农,高志良.乙型肝炎肝衰竭发生机制中的三重打击[J].传染病信息,2009(5):276-279.
[6]Ousingsawat J,Cabrita I,Wanitchakool P,et al.Ca2+signals,cell membrane disintegration,and activation of TMEM16F during necroptosis[J].Cell Mol Life Sci,2017,74(1):173-181.
[7]Shieh CH,Heinrich A,Serchov T,et al.P2X7-dependent,but differentially regulated release of IL-6,CCL2,and TNFalpha in cultured mouse microglia[J].Glia,2014,62(4):592-607.
[8]Picollo A,Malvezzi M,Accardi A.TMEM16 proteins:unknown structure and confusing functions[J].J Mol Biol,2015,427(1):94-105.
[9]Gicquel T,Le DaréB,Boichot E,et al.Purinergic receptors:new targets for the treatment of gout and fibrosis[J].Fundamental&Clinical Pharmacology,2017,31(2):136-146.
[10]Souza VDCG,Dos Santos JT,Cabral FL,et al.Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease[J].Microbial Pathogenesis,2017(104):32-38.
[11]王丽雁,蔡文琴,陈鹏慧.P2X7受体在OPCs缺氧缺血性损伤中作用的初步研究[J].重庆医学,2010,39(21):2895-2897.
[12]Wanke D,Mauch-Mücke K,Holler E,et al.Human betadefensin-2 and-3 enhance pro-inflammatory cytokine expression induced by TLR ligands via ATP-release in a P2X7R dependent manner[J].Immunobiology,2016,221(11):1259-1265.
[13]Park JH,Williams DR,Lee JH,et al.Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion[J].J Med Chem,2016,59(16):7410-7430.