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

关键词:  龙胆泻肝汤  急性肝性脑病  硫代乙酰胺  血氨

Key words:  Longdan Xiegan Decoction  acute hepatic encephalopathy  TAA  blood ammonia

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10mL/kg生理盐水，阳性药组灌胃给予6g/kg乳果糖，龙胆泻肝汤组灌胃给予7g/kg龙胆泻肝汤，连续给药7d，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TAA300mg/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。

Abstract:

[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-α in serum were lower than those in model group;the histopathological injury and fibrosis of livers were improved;the levels of GBAB and MDA in rat brain decreased significantly, and Glu increased significantly(P<0.01). [Conclusion] Longdan Xiegan Decoction can improve the learning and memory ability of model rats, reduce the content of ammonia in vivo, and improve the liver injury. It can reduce the content of inflammatory factors in serum of model rats, regulate the levels of GABA, Glu and MDA in brain, and play a role in treating acute hepatic encephalopathy.