山莨菪碱对大鼠急性肝损伤的保护作用及其机制

Protective effect of anisodamine on acute liver injury in rats and its potential mechanism

目的：探讨山莨菪碱对急性肝损伤的保护作用及其作用机制。方法：雄性Ｗｉｓｔａｒ大鼠１８只随机分为３组：正常对照组、模型组和山莨菪碱组。以Ｄ半乳糖胺加内毒素脂多糖制成大鼠急性肝损伤模型。用山莨菪碱（２０ｍｇ／ｋｇ）预处理模型鼠。观察３组大鼠肝酶含量，血清一氧化氮（ＮＯ）含量，肝组织中ＮＯ、丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）活性及肝组织病理学变化。结果：山莨菪碱组大鼠丙氨酸转氨酶〔ＡＬＴ（６６６±２６７）Ｕ〕、天冬氨酸转氨酶〔ＡＳＴ（１０５９±４０８）Ｕ〕及血清总胆红素〔ＴＢＩＬ（７．２２±５．６２）μｍｏｌ／Ｌ〕均明显低于模型组〔分别为（２３５２±６９８）Ｕ，（３５４９±７１７）Ｕ和（２０．７１±５．９２）μｍｏｌ／Ｌ〕，Ｐ均＜０．０１；伴随着山莨菪碱对血及肝组织中ＮＯ过量合成的抑制，肝组织中ＭＤＡ降低、ＳＯＤ增高（Ｐ均＜０．０１）。山莨菪碱组肝组织病理改变较模型组明显减轻。结论：山莨菪碱对大鼠急性肝损伤有保护作用，保护作用可能与山莨菪碱抑制ＮＯ的过量产生及清除自由基有关。

Objective:To study the protective effect of anisodamine on acute liver injury and its potential mechanism.Methods:Rats were injected intraperitoneally with DGalactosamine (DGalN, 0 6 g/kg ) plus lipopolysaccharide (LPS,0 1 mg/kg) to induce acute liver injury.Animals were randomly divided into normal control group,liver injury group and treatment group (pretreatment with anisodamine 20 mg/kg).Twelve hours later,serum and liver tissues were collected to measure liver function parameters,lipid peroxidation (malondialdehyde,MDA),nitric oxide (NO) levels and superoxide dismutase (SOD) activity,and pathology change of liver was also observed.Results:Serum alanine aminotransferase ALT(666±267)U ,aspartate aminotransferase AST(1 059±408)U and total bilirubin TBIL(7 22±5 62)μmol/L in anisodaminetreated group were significantly lower than those in animals without treatment (2 352±698)U,(3 549±717)U,(20 71±5 92)μmol/L respectively,all P <0 01 .Pretreatment with anisodamine,it obviously reduced the elevation of NO levels both in serum and tissue compared to liver injury group,and similar changes were also observed in tissue MDA levels,while tissue SOD activities were markedly increased in animals by treated with anisodamine (all P <0 01).Conclusions:Anisodamine has protective effect on acute liver injury by inhibition of NO production and scavenging free radical.