6,7-二乙酰黄芩素对大鼠急性肝性脑病的防治作用及机制研究  

Preventive effect and mechanism of baicalein 6, 7-diacetate on acute hepatic encephalopathy in rats

作　　者：黄楠楠 胡鹏[1] 吴增光 杜乐梅 范栢爽 王丽莉[1] 何新[1,2] HUANG Nannan;HU Peng;WU Zengguang;DU Lemei;FAN Baishuang;WANG Lili;HE Xin(Tianjin University of Traditional Chinese Medicine,Tianjin 30160,China;Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]天津中医药大学,天津301617 [2]广东药科大学,广东广州510006

出　　处：《药物评价研究》2020年第10期1957-1963,共7页Drug Evaluation Research

基　　金：广东省自然科学基金资助项目(2020A1515010156);广东省普通高校重点领域专项(2019KZDZX1006)。

摘　　要：目的研究6,7-二乙酰黄芩素对硫代乙酰胺致大鼠急性肝性脑病模型的防治作用及机制。方法 Wistar雄性大鼠60只,随机分为对照组、模型组、乳果糖(阳性药,6 g/kg)组和6,7-二乙酰黄芩素低、中、高剂量(6.25、12.50、25.00 mg/kg)组,每天ig给药1次,连续给药7 d。第5天给药结束后,除对照组外,采用硫代乙酰胺(300 mg/kg)连续ip 2 d建立大鼠肝性脑病模型。观察大鼠状态,考察大鼠肝性脑病评分与死亡率;测定各组大鼠血氨、结肠p H值、血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、总胆红素(TBIL)水平;采用苏木素-伊红(HE)染色法观察大鼠肝组织病理学变化;采用ELISA试剂盒法检测大鼠脑组织中γ-氨基丁酸(GABA)、谷氨酸(Glu)、血浆中的5-羟色胺(5-HT)、去甲肾上腺素(NE)的含量;采用Western Blotting试验测定脑组织中GABA-α1蛋白的表达。结果造模48 h后,与模型组比较,6,7-二乙酰黄芩素高剂量组大鼠体质量显著升高(P<0.05),肝性脑病评分显著降低(P<0.05);各剂量组死亡率均降低;中、高剂量组血清ALT、AST、ALP和TBIL水平均显著降低(P<0.05);低、中、高剂量组血氨水平显著降低(P<0.05、0.01);中、高剂量组结肠p H显著降低(P<0.05、0.01);中、高剂量组大鼠肝脏组织病理学损伤明显改善;各剂量组脑组织中GABA水平显著降低(P<0.01);中、高剂量组血浆中5-HT水平显著降低(P<0.01);高剂量组血浆中NE水平显著降低(P<0.01);高剂量组脑组织中Glu含量显著增加(P<0.01);高剂量脑组织中GABA-α1蛋白表达显著降低(P<0.05)。结论 6,7-二乙酰黄芩素对肝脏具有保护作用,对急性肝性脑病具有防治作用,其机制可能与降低血氨、降低结肠p H、调节神经递质水平、抑制相关神经递质受体的表达有关。Objective To investigate the preventive effect and mechanism of baicalein 6,7-diacetate(BD) on thioacetamide-induced hepatic encephalopathy in rats.Methods Tatolly sixty male Wistar rats were randomly divided into control group, model group,lactulose(positive drug, 6 g/kg) group and 6,7-diacetyl baicalein low, medium and high dose(6.25, 12.50 and 25.00 mg/kg) groups,ig once a day for seven days.A rat model of actue hepatic encephalopathy was established by continuous ip injection of thioacetamide for two days.To observe the status of rats and investigate the stage of hepatic encephalopathy and mortality in rats.The levels of ammonia, AST, ALT, ALP and TBIL in serum and colonic p H of rats in each group were measured.HE staining was used to evaluate the pathological changes of liver in rats.The level of GABA and glutamic acid(Glu) in rat brain, and the level of serotonin(5-HT) and norepinephrine(NE) in plasma were determined by ELISA.The expression of GABA-α1 in brain tissue was determined by Western Blotting.Results 48 hours after modeling, compared with the model group, BD high-dose group significantly increased body weight(P < 0.05), hepatic encephalopathy score decreased significantly(P < 0.05), mortality of each dose group was reduced, serum ALT, AST, ALP and TBIL levels were significantly decreased in middle and high dose groups(P <0.05);blood ammonia level in low, medium and high dose groups was significantly decreased(P < 0.05, 0.01);colon p H wassignificantly decreased in middle and high dose groups.Compared with model group, the level of GABA in brain tissue was significantly decreased(P < 0.01);The level of 5-HT in the middle and high-dose groups was significantly decreased(P < 0.01);the plasma NE level in the high-dose group was significantly decreased(P < 0.01);the Glu content in the brain tissue of the high-dose group was significantly increased(P < 0.01);the expression of GABA-α1 protein in the high-dose group was significantly decreased(P < 0.05).Conclusion BD has a protective effect on the liver

关 键 词：肝性脑病 6 7-二乙酰黄芩素 硫代乙酰胺 血氨 神经递质 

分 类 号：R965[医药卫生—药理学]