目的 研究6，7-二乙酰黃芩素對(duì)硫代乙酰胺致大鼠急性肝性腦病模型的防治作用及機(jī)制。方法 Wistar雄性大鼠60只，隨機(jī)分為對(duì)照組、模型組、乳果糖（陽性藥，6 g/kg）組和6，7-二乙酰黃芩素低、中、高劑量（6.25、12.50、25.00 mg/kg）組，每天ig給藥1次，連續(xù)給藥7 d。第5天給藥結(jié)束后，除對(duì)照組外，采用硫代乙酰胺（300 mg/kg）連續(xù)ip 2 d建立大鼠肝性腦病模型。觀察大鼠狀態(tài)，考察大鼠肝性腦病評(píng)分與死亡率；測(cè)定各組大鼠血氨、結(jié)腸pH值、血清天冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、堿性磷酸酶（ALP）、總膽紅素（TBIL）水平；采用蘇木素-伊紅（HE）染色法觀察大鼠肝組織病理學(xué)變化；采用ELISA試劑盒法檢測(cè)大鼠腦組織中γ-氨基丁酸（GABA）、谷氨酸（Glu）、血漿中的5-羥色胺（5-HT）、去甲腎上腺素（NE）的含量；采用Western Blotting試驗(yàn)測(cè)定腦組織中GABA-α₁蛋白的表達(dá)。結(jié)果 造模48 h后，與模型組比較，6，7-二乙酰黃芩素高劑量組大鼠體質(zhì)量顯著升高（P<0.05），肝性腦病評(píng)分顯著降低（P<0.05）；各劑量組死亡率均降低；中、高劑量組血清ALT、AST、ALP和TBIL水平均顯著降低（P<0.05）；低、中、高劑量組血氨水平顯著降低（P<0.05、0.01）；中、高劑量組結(jié)腸pH顯著降低（P<0.05、0.01）；中、高劑量組大鼠肝臟組織病理學(xué)損傷明顯改善；各劑量組腦組織中GABA水平顯著降低（P<0.01）；中、高劑量組血漿中5-HT水平顯著降低（P<0.01）；高劑量組血漿中NE水平顯著降低（P<0.01）；高劑量組腦組織中Glu含量顯著增加（P<0.01）；高劑量腦組織中GABA-α₁蛋白表達(dá)顯著降低（P<0.05）。結(jié)論 6，7-二乙酰黃芩素對(duì)肝臟具有保護(hù)作用，對(duì)急性肝性腦病具有防治作用，其機(jī)制可能與降低血氨、降低結(jié)腸pH、調(diào)節(jié)神經(jīng)遞質(zhì)水平、抑制相關(guān)神經(jīng)遞質(zhì)受體的表達(dá)有關(guān)。

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 pH 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 pH was significantly 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 and a preventive effect on acute hepatic encephalopathy in rats. The mechanism may be related to reducing blood ammonia and colon pH, regulating neurotransmitter level, and inhibiting the expression of related neurotransmitter receptors.

R965

廣東省自然科學(xué)基金資助項(xiàng)目（2020A1515010156）；廣東省普通高校重點(diǎn)領(lǐng)域?qū)ｍ?xiàng)（2019KZDZX1006）