甘草次酸和苦参碱对实验性急性胆管消失综合征的防治作用

目的探讨甘草次酸(GA)和苦参碱(MT)对急性胆管消失综合征(AVBDS)的防治作用,为AVBDS的药物治疗提供实验依据。方法应用异硫氰酸-1-萘酯(ANIT)制备大鼠AVBDS模型。预防性给药,分别给大鼠ipGA,MT和地塞米松(DEX)(均10mg.kg-1),每12h给药1次,共4次,第2次给药后30min给予ANIT造模。治疗性给药,在造模后3或12h给予GA,MT或DEX,每12h给药1次,共2次。同时设正常对照组和ANIT模型组。所有动物在造模后36h进行胆排泄实验测定2h胆汁流量和胆汁中酮洛芬葡萄糖醛酸结合物(KPG)累计胆排泄率,随后观察肝功能生化指标和肝组织病理改变。结果造模前给予DEX明显减轻胆管损伤,对肝细胞损伤无作用。造模后3h给予DEX不能减轻AVBDS,造模后12h给予DEX,大鼠血清谷丙转氨酶(GPT)活性较模型组升高,并伴有严重的汇管区胆管消失和灶状肝细胞坏死。造模前、造模后3h分别给予GA或MT,均不同程度地改善ANIT诱导的血清总胆红素(Tbil)水平升高,GPT、碱性磷酸酶和γ-谷酰转移酶活性升高,以及胆汁流量及KPG胆汁累计排泄减少。造模后12h给予GA和MT,对ANIT所致肝损伤无明显改善作用。结论在实验性AVBDS早期,GA和MT对AVBDS具有一定的防治作用,且在一定程度上优于DEX。

Protection of glycyrrhetinic acid and matrine against experimental acute vanishing bile duct syndrome

AIM To explore the effects of glycyrrhetinic acid (GA) and matrine (MT) on acute vanishing bile duct syndrome (AVBDS) and provide information for AVBDS treatment. METHODS AVBDS rat model was induced by α-naphthylisothiocyanate (ANIT). For pretreatment: the rats were treated (ip) with GA (10 mg·kg^-1), MT (10 mg·kg^-1) and dexamethasone (DEX, 10 mg·kg^-1), respectively, once per 12 h for 4 times. ANIT was given 30 min after the 2nd administration of GA, MT or DEX. For remedial treatment: the rats were administered with ANIT 3 or 12 h before the 1st treatment of GA, MT or DEX, once per 12 h, twice. Normal control and ANIT model control groups were designed. The bile flow and accumulative bile excretion of ketoprofen glucuronide of all the rats were measured 36 h after ANIT administration. The level of serum total bilirubin (Tbil) and activities of serum glutamic-pyruvic transaminase (GPT), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) were detected, and histopathological changes of rat livers were also observed. RESULTS DEX pretreatment protected cholangiocytes rather than hepatocytes from damages. Remedial treatment with DEX 3 h after ig ANIT had no influence on ANIT toxicity. Notably, remedial treatment with DEX 12 h after ANIT enhanced ANIT toxicity as demonstrated by the elevated GPT activity and a severe loss of majority interlobular ducts, accompanied with focus hepatocytes necrosis. However, pretreatment and remedial treatment with GA or MT 3 h after ANIT attenuated both bile duct and hepatocyte damages induced by ANIT. The serology and morphological parameters of liver injury were significantly reduced, and the bile excretion inhibited by ANIT was significantly ameliorated. Remedial treatment with GA or MT 12 h after ANIT exhibited few protective effects against ANIT-induced liver damages. CONCLUSION GA and MT exhibit protection against ANIT-induced AVBDS in the initial phase of the impairment, and this effect might be better than DEX.