大黄对幼鼠肝内胆汁淤积的作用机制

Mechanism of Action of Rhubarb on Intrahepatic Cholestasis in Infantile Rats

目的探讨中药大黄对幼鼠肝内胆汁淤积的作用机制。方法90只SD幼鼠随机分成大黄治疗组、未治疗组、熊去氧胆酸(UDCA)组、UDCA+D组(熊去氧胆酸联合泼尼松)、空白对照组;用α-萘异硫氰酸酯(ANIT)灌胃建立幼鼠胆汁淤积性黄疸模型,检测不同时间其血清总胆红素(TB)、结合胆红素(DB)、ALT、碱性磷酸酶(ALP)和总胆汁酸(TBA)水平;制作肝组织匀浆,检测肝组织一氧化氮(NO)、丙二醛(MDA)、总抗氧化能力(T-AOC)水平。结果实验结果表明成功构建幼鼠胆汁淤积性黄疸模型。大黄治疗组血清TB、DB、ALT、ALP及TBA明显低于未治疗组(Pa(0.05);中药大黄在退黄、降低ALP、TBA方面优于UDCA和UDCA+D组;未治疗组肝组织T-AOC明显低于空白对照组,而NO和MDA明显高于空白对照组,经大黄治疗后肝组织T-AOC明显高于未治疗组,NO和MDA明显低于未治疗组(P<0.05)。结论大黄能明显降低血清TB、DB、ALT、ALP及TBA水平,显著降低胆汁酸毒性作用,减轻肝损伤;大黄治疗肝内胆汁淤积作用机制可能与降低肝组织NO水平、减轻脂质过氧化反应、增强细胞保护作用和提高抗氧化损伤能力有关。

Objective To explore mechanism of action of rhubarb on intrahepatic eholestasis in infantile rats. Methods Ninety Sprague - Dawley （SD） infantile rats were randomly divided into 5 groups ： treatment group of rhubarb, untreated group, treatment eontrol group 1 of ursodeoxyehlie acid（ UDCA）, treatment eontrol group 2 of UDCA and dehasone, and eontrol group not treated with α-naphthyl isothioeyanate （ANIT） and any other treatments. Jaundiee model of intrabepatie eholestasis was established in infantile rats by ANIT. At the time of the 2^nd , 3^nd, and 4^th week, the eoneentrations of serum total bilirubin （ TB ）, direet bilirubin （ DB ）, ALT, alkaline phosphatase （ ALP ）, total bile aeid （TBA） and TBA were assessed by automatie biochemieal analyzer. The eoneentrations of nitrogen monoxide （ NO ）, maleie dialdehyde （MDA） and the ability of total antioxidation （ T - AOC ） in liver tissues were measured. Results It was demonstrated that the animal model of hepatie jaundiee with eholestasis was sueeessfully established. The levels of serum DB, TB, ALP, ALT and TBA were signifieantly lower in the treatment group of rhubarb eompared with those in the untreated group （ P〈0.05 ）. Meanwhile,better effects of relieving the jaundiee and decreasing the ALP and TBA levels eould be observed in rhubarb treatment group eompared with the UDCA group or treatment group of eombined use of UDCA and deltasone. The level of T - AOC in liver tissue was mueh lower in untreated group eompared with that in the untreated eontrol group,while NO and MDA were mueh higher. But after the rhubarb treatment,the levels of T - AOC in liver tissue inereased and beeame mueh higher than that of in the untreated group,while the NO and MDA became lower than that in the untreated group （ P 〈 0.05 ）. Conclusions Rhubarb remarkably reduees the eoneentrations of serum TB, DB, ALT, ALP and TBA, relieves the toxieity of bile aeid and inhibits the hepatie injury. Mechanisms of rhubarb aetion on intrahepatic eholestasis relate with may be related to deereasing the level of NO in liver tissue,proteeting eells as well as inereasing the ability of elearanee produets from oxygen - derived free radicals and antioxidant damage.