麻黄升麻汤对肝硬化腹水并感染大鼠血清炎性因子的干预作用
|
摘要
目的:研究麻黄升麻汤对肝硬化腹水并感染大鼠血清炎性因子的干预作用,并从PI3K/Akt1信号转导通路探讨其作用机制。方法:将80只SD成年健康大鼠随机分为空白组,模型组,溶媒对照组,低、中、高剂量组。采用四氯化碳联合乙醇、高脂饮食法建立肝硬化腹水大鼠模型。全自动生化仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清白蛋白(ALB);显微镜下计数法检测腹水多形核白细胞(PMN);ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平;Western blot法检测肝组织中PI3K p85、p-Akt1蛋白表达量。结果:经干预治疗后,与模型组、溶媒对照组比较,高剂量组、中剂量组ALT、AST、TNF-α、IL-6、IL-8、PMN及肝组织中PI3K p85、p-Akt1蛋白表达量显著降低(P<0.05),且高剂量组较中、低剂量组下降更显著(P<0.05)。结论:麻黄升麻汤可明显改善肝硬化腹水并感染大鼠肝功能,降低血清炎症细胞因子水平,抑制局部炎性反应,其作用机制可能与抑制PI3K/Akt1信号通路的激活有关。
Objective: To study the intervention effect of Mahuang Shengma Decoction on serum inflammatory factors in rats with cirrhotic ascites and infection, and to explore its mechanism through PI3 K/Akt1 signaling pathway. Methods: Eighty SD adult healthy rats were randomly divided into the control group, the model group, the Vehicle group, and the low, middle and high dose groups of Mahuang Shengma Decoction. The rat model of cirrhotic ascites was established by carbon tetrachloride combined with ethanol and high fat diet. Using automatic biochemical analyzer to detect the serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) and serum albumin(ALB); microscopy detection of ascites polymorphonuclear leukocytes(PMN); Serum levels of tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and interleukin-8(IL-8) were detected by ELISA method;The expressions of PI3 K p85 and p-Akt1 protein in liver tissues were detected by Western blot method. Results: After treatment,compared with the model group and solvent control group, the expression of ALT, AST, TNF-α, IL-6, IL-8, PMN and PI3 K p85,p-Akt1 protein of liver tissue in high dose group, middle dose group decreased significantly(P<0.05), and high dose group were lower than those in middle and low dose groups(P<0.05). Conclusion: Mahuang Shengma Decoction could obviously improve the liver function of rats with cirrhotic ascites complicated by infection, reduce the level of inflammatory cytokines in serum and then inhibit the local inflammatory reaction, the mechanism of action may be related to the inhibition of activation of PI3 K/Akt1 signaling pathway.
Objective: To study the intervention effect of Mahuang Shengma Decoction on serum inflammatory factors in rats with cirrhotic ascites and infection, and to explore its mechanism through PI3 K/Akt1 signaling pathway. Methods: Eighty SD adult healthy rats were randomly divided into the control group, the model group, the Vehicle group, and the low, middle and high dose groups of Mahuang Shengma Decoction. The rat model of cirrhotic ascites was established by carbon tetrachloride combined with ethanol and high fat diet. Using automatic biochemical analyzer to detect the serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) and serum albumin(ALB); microscopy detection of ascites polymorphonuclear leukocytes(PMN); Serum levels of tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6) and interleukin-8(IL-8) were detected by ELISA method;The expressions of PI3 K p85 and p-Akt1 protein in liver tissues were detected by Western blot method. Results: After treatment,compared with the model group and solvent control group, the expression of ALT, AST, TNF-α, IL-6, IL-8, PMN and PI3 K p85,p-Akt1 protein of liver tissue in high dose group, middle dose group decreased significantly(P<0.05), and high dose group were lower than those in middle and low dose groups(P<0.05). Conclusion: Mahuang Shengma Decoction could obviously improve the liver function of rats with cirrhotic ascites complicated by infection, reduce the level of inflammatory cytokines in serum and then inhibit the local inflammatory reaction, the mechanism of action may be related to the inhibition of activation of PI3 K/Akt1 signaling pathway.
引文
[1]李军红,罗利飞.双歧杆菌四联活菌片对肝硬化自发性细菌性腹膜炎患者肠黏膜屏障和炎症因子的影响.中国微生态学杂志,2013,25(12):1419-1422
[2]段惠春,王学红,范仲麟,等.细胞因子失衡促进肝硬化形成的研究进展.医学综述,2010,16(10):1441-1444
[3]Tandon P,Garcia-Tsao G.Bacterial infections,sepsis,and multiorgan failure in cirrhosis.Semin Liver Dis,2008,28(1):26-42
[4]李灿,周晓玲,陈峭,等.麻黄升麻汤治疗原发性肝癌TACE术后患者的疗效观察.时珍国医国药,2018,29(1):114-116
[5]唐倩.大鼠肝硬化模型的制备及其在白蛋白药效学评价中的应用.北京:中国人民解放军军事医学科学院,2012
[6]Satoshi H,Hitoshi N,Takashi Y,et al.Effectiveness of recombinant human serum albumin in treatment of ascites in liver cirrhosis:Evidence from animal model.Gen Pharmacol,1998,31(5):811
[7]詹纯列,肖育华,李新春,等.普通级、SPF级SD、Wistar大鼠血液生化常值的测定与比较.中国比较医学杂志,2004,14(2):94
[8]张兴光,冯志杰.肝硬化自发性细菌性腹膜炎的诊断及治疗进展.世界华人消化杂志,2015,23(3):388-395
[9]刘小转,李三强,任江涛,等.HSP70I、IL-6和TNF-α在CCl4诱导的小鼠急性肝损伤组织中的表达及意义.山东医药,2011,51(35):17-19
[10]马颂华.IL-6神经保护作用的钙离子通道机制及信号转导途径.苏州:苏州大学,2014,10:105
[11]程勇,言红健,孟杰,等.非酒精性脂肪性肝病患者肝损伤程度与IL-18、IL-8含量的相关性.中国老年学杂志,2011,31(9):1528-1529
[12]施凤,朱萱.NOX介导的MAPK、PI3K/Akt信号通路与肝纤维化的研究进展.世界华人消化杂志,2012,20(28):2685-2690
[13]Yang F J,He Y H,Zhou J H.Fenofibrate pre-treatment suppressed inflammation by activating phosphoinositide 3kinnase/protein kinase B(PI3K/AKT)signaling in renalischemia-repefusion injury.Journal of Huazhong University of Science and Technology(Medical Science),2015,35(1):58-63
[14]Gui B,Hua F,Chen J,et al.Protective effects of pretreatment with oleanolic scid in rats in the acute phase of hepaticischemiareperfusion injury:Role of the PI3K/AKT pathway.Mediators Inflamm,2013,2014(1):143-146
[15]Yin X,Wang X,Fan Z,et al.Hyperbaric Oxygen preconditioningat tenuates myocardium Ischeia-Reperfusion injury through upregulation of Heme oxygenase1 expression PI3K/AKT/Nrf2 pathway involved.J Cardiovasc Pharmascol Ther,2015,20(4):428-438
[16]程飞,张献全,宋孟龙,等.PBK/Akt/mTOR信号通路参与缺氧诱导因子-1在急性胰腺炎大鼠的表达调节.中国急救医学,2010,30(4):330-334
[17]周晓玲,刘莹,余静芳,等.从六经之厥阴病论治阳虚血瘀型乙肝后肝硬化55例.环球中医药,2016,9(7):870-873
[18]周晓玲,余静芳,刘莹,等.从太阴病论治乙型肝炎后肝硬化代偿期患者肠道微生态的临床研究.辽宁中医杂志,2016,43(11):2330-2332
[19]赵杰,余林中,方芳,等.麻黄-甘草药对的抗炎作用及机制研究.中国实验方剂学杂志,2012,18(15):163-166
[20]张均克.升麻解毒药对在方剂中的作用.中华中医药杂志,2011,26(8):844-846
[2]段惠春,王学红,范仲麟,等.细胞因子失衡促进肝硬化形成的研究进展.医学综述,2010,16(10):1441-1444
[3]Tandon P,Garcia-Tsao G.Bacterial infections,sepsis,and multiorgan failure in cirrhosis.Semin Liver Dis,2008,28(1):26-42
[4]李灿,周晓玲,陈峭,等.麻黄升麻汤治疗原发性肝癌TACE术后患者的疗效观察.时珍国医国药,2018,29(1):114-116
[5]唐倩.大鼠肝硬化模型的制备及其在白蛋白药效学评价中的应用.北京:中国人民解放军军事医学科学院,2012
[6]Satoshi H,Hitoshi N,Takashi Y,et al.Effectiveness of recombinant human serum albumin in treatment of ascites in liver cirrhosis:Evidence from animal model.Gen Pharmacol,1998,31(5):811
[7]詹纯列,肖育华,李新春,等.普通级、SPF级SD、Wistar大鼠血液生化常值的测定与比较.中国比较医学杂志,2004,14(2):94
[8]张兴光,冯志杰.肝硬化自发性细菌性腹膜炎的诊断及治疗进展.世界华人消化杂志,2015,23(3):388-395
[9]刘小转,李三强,任江涛,等.HSP70I、IL-6和TNF-α在CCl4诱导的小鼠急性肝损伤组织中的表达及意义.山东医药,2011,51(35):17-19
[10]马颂华.IL-6神经保护作用的钙离子通道机制及信号转导途径.苏州:苏州大学,2014,10:105
[11]程勇,言红健,孟杰,等.非酒精性脂肪性肝病患者肝损伤程度与IL-18、IL-8含量的相关性.中国老年学杂志,2011,31(9):1528-1529
[12]施凤,朱萱.NOX介导的MAPK、PI3K/Akt信号通路与肝纤维化的研究进展.世界华人消化杂志,2012,20(28):2685-2690
[13]Yang F J,He Y H,Zhou J H.Fenofibrate pre-treatment suppressed inflammation by activating phosphoinositide 3kinnase/protein kinase B(PI3K/AKT)signaling in renalischemia-repefusion injury.Journal of Huazhong University of Science and Technology(Medical Science),2015,35(1):58-63
[14]Gui B,Hua F,Chen J,et al.Protective effects of pretreatment with oleanolic scid in rats in the acute phase of hepaticischemiareperfusion injury:Role of the PI3K/AKT pathway.Mediators Inflamm,2013,2014(1):143-146
[15]Yin X,Wang X,Fan Z,et al.Hyperbaric Oxygen preconditioningat tenuates myocardium Ischeia-Reperfusion injury through upregulation of Heme oxygenase1 expression PI3K/AKT/Nrf2 pathway involved.J Cardiovasc Pharmascol Ther,2015,20(4):428-438
[16]程飞,张献全,宋孟龙,等.PBK/Akt/mTOR信号通路参与缺氧诱导因子-1在急性胰腺炎大鼠的表达调节.中国急救医学,2010,30(4):330-334
[17]周晓玲,刘莹,余静芳,等.从六经之厥阴病论治阳虚血瘀型乙肝后肝硬化55例.环球中医药,2016,9(7):870-873
[18]周晓玲,余静芳,刘莹,等.从太阴病论治乙型肝炎后肝硬化代偿期患者肠道微生态的临床研究.辽宁中医杂志,2016,43(11):2330-2332
[19]赵杰,余林中,方芳,等.麻黄-甘草药对的抗炎作用及机制研究.中国实验方剂学杂志,2012,18(15):163-166
[20]张均克.升麻解毒药对在方剂中的作用.中华中医药杂志,2011,26(8):844-846