龙胆泻肝汤对大鼠急性肝性脑病的防治作用研究  

Study on the preventive effect of Longdan Xiegan Decoction on acute hepatic encephalopathy in rats

作　　者：吴梓君 范栢爽 罗嘉仪 魏欣 李思勤 王丽莉[1] 何新[1,2,3] WU Zijun;FAN Baishuang;Luo Jiayi;Wei Xin;Li Siqin;WANG Lili;HE Xin(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]天津中医药大学,天津301617 [2]中国医学科学院/北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050 [3]广东药科大学,广州510006

出　　处：《天津中医药大学学报》2022年第6期746-753,共8页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：广东省重点学科科研项目(2019GDXK0014);天然活性物质与功能国家重点实验室开放基金项目(GTZK202010)。

摘　　要：[目的]研究龙胆泻肝汤对硫代乙酰胺(TAA)所致大鼠急性肝性脑病的防治作用。[方法]选择SPF级Wistar大鼠为研究对象,随机分为正常组、模型组、阳性药组(乳果糖)和龙胆泻肝汤组,每组8只。正常组和模型组每日灌胃给予10 mL/kg生理盐水,阳性药组灌胃给予6 g/kg乳果糖,龙胆泻肝汤组灌胃给予7 g/kg龙胆泻肝汤,连续给药7 d,每日1次。于第5天给药结束后开始造模,除正常组外,其余各组大鼠均腹腔注射TAA 300 mg/kg,连续两天。通过脑功能评分和Morris水迷宫评价大鼠的学习和记忆能力;检测血氨和结肠内容物pH值变化;采用肝、脑脏器系数、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBiL)的浓度和肝脏病理切片反映组织损伤;采用酶联免疫吸附法(ELISA)检测大鼠血清中白介素-6(IL-6)和肿瘤坏死因子α(TNF-α)水平,脑中γ-氨基丁酸(GABA)、谷氨酸(Glu)和丙二醛(MDA)的含量。[结果]与模型组相比,龙胆泻肝汤组大鼠的脑功能评分显著增加,逃避潜伏期显著降低,穿环指数显著增加;血氨和结肠内容物pH值显著降低(P<0.001);其对脑脏器系数降低显著(P<0.001),对肝脏器系数改善不明显;生化指标ALT、AST、ALP和TBiL显著降低(P<0.001);血清中炎症因子IL-6和TNF-α显著低于模型组;改善大鼠肝组织病理学损伤及纤维化;大鼠脑中GBAB和MDA显著降低,Glu水平显著升高(P<0.01)。[结论]龙胆泻肝汤可通过改善模型大鼠的学习和记忆能力,降低体内氨的含量,改善肝脏损伤;减少模型大鼠血清中炎症因子的含量,调节脑内GABA、Glu神经递质及MDA水平,发挥治疗肝性脑病的作用。[Objective]To investigate the preventive and therapeutic effects of Longdan Xiegan Decoction on acute hepatic encephalopathy induced by TAA in rats.[Methods]The SPF Wistar rats were randomly divided into normal group,model group,positive drug group(Lactulose)and Longdan Xiegan Decoction group,with 8 rats in each group.Normal group and model group were given 10 mL/kg normal saline,positive drug group was given 6 g/kg lactulose,and Longdan Xiegan Decoction group was given 7 g/kg Longdan Xiegan Decoction,once a day,for consecutive 7 d.Model of acute hepatic encephalopathy was established after the end of administration on the fifth day.Except for the normal group,other groups were intraperitoneally injected with TAA 300 mg/kg for two days.The brain function score and Morris water maze were used to evaluate the learning and memory ability of rats;the blood ammonia and pH of colon contents were measured;the organ coefficient of liver and brain,alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBiL)and liver pathological section were used to reflect the tissue injury;the leves of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum and the the contents of gamma aminobutyric acid(GABA),glutamic acid(Glu)and malonaldehyde(MDA)in brain were detected by enzyme-linked immunosorbent assay(ELISA).[Results]Compared with the model group,the brain function score of Longdan Xiegan Decoction group was significantly increased;both the latencies to find a hidden plateform in the water maze and the annulus-crossing index had significantly difference;the blood ammonia and pH of colon contents decreased significantly(P<0.001);the organ coefficient of brain significantly increased(P<0.001),while that of liver showed no difference;the values of ALT,AST,ALP and TBiL decreased significantly(P<0.001);the inflammatory cytokines of IL-6 and TNF-αin serum were lower than those in model group;the histopathological injury and fibrosis of livers were improved;the levels of GBAB and

关 键 词：龙胆泻肝汤 急性肝性脑病 硫代乙酰胺 血氨 

分 类 号：R285.5[医药卫生—中药学]