山莨菪碱对实验性肝损伤的保护及其机制的研究

Protective Effects and Mechanisms of Anisodamine on Experimental Liver Injury

目的 探讨山莨菪碱对实验性肝损伤的疗效及其作用机制。方法 应用ANIT和CCl4分别诱发大鼠肝内胆汁淤积及小鼠肝损伤的模型 ,使用山莨菪碱治疗后观察、测定给药组与对照组的肝组织病理切片和生化指标、肝组织中的Ca2 + 含量、总抗氧化能力、丙二醛的含量及山莨菪碱对CCl4中毒小鼠戊巴比妥钠睡眠时间的影响。结果 山莨菪碱能明显对抗ANIT和CCl4所致的ALT、ALP、Bil升高和血清Tp下降 (P <0 0 1) ,并且使肝细胞和胆管上皮细胞变性、坏死显著减轻。检测山莨菪碱治疗组肝匀浆Ca2 + 含量为( 15 6 9± 3 2 8) μg/g、丙二醛为 ( 62 9± 17 4)nmol/ml及总抗氧化能力为 ( 3 1 9± 8 5 )U/ml ,CCl4中毒小鼠腹腔注射戊巴比妥钠后的睡眠时间为 ( 13 0 9± 3 5 9)min。提示山莨菪碱能明显减低肝匀浆含量 (P <0 0 5 )、脂质过氧化产物丙二醛含量 ,提高机体总抗氧化能力 (P<0 0 1)且可缩短CCl4中毒小鼠腹腔注射戊巴比妥钠后的睡眠时间 ( P <0 0 1)。结论 山莨菪碱对实验性肝损伤具有保护作用 ,其疗效与茵栀黄注射液和肝炎灵相似 ( P >0 0 5 ) ,其作用机制可能与M受体阻断、Ca2 +

Objective To investigate the protective effects and the mechanisms of anisodamine on experimental liver damage. Methods The experimental liver injury model was established by ANIT and CCl 4.Studies were made after ANIT or CCl 4 administration,and the control group compared with the experimental groups which were treated by anisodamine on the pathologic morphology, biochemical indices and the contents of Ca 2+ ,MDA and the ability of total antioxidation in the liver.Effects of anisodamine on sleeping time of the mice toxicated by given sodium phenobarbital were also determined.Results The elevation of ALT, ALP, BiL, CHE and the decrease of serum protein in ANIT or CCl 4 liver damage were significantly improved by treatment with anisodamine .It also remarkably diminished the hepato-cellular and chole-epthelial-cellular degeneration and necrosis induced by ANIT or CCl 4.The contents of Ca 2+ ,MDA and the ability of total antioxidation in the liver were all decreased by treatment with anisodamine. The sleeping time induced by sodium phenobarbital in the toxicated mice was reduced by anisodamine. Conclusion Anisodamine have significant protective effects on liver injury of intrahepatic cholestasis and chemical hepatitis and the mechanism may be associated with blocking M-receptor and enhancing antioxidation and antitoxic activity in liver.