摘要
目的观察三黄茵赤汤防治D-氨基半乳糖(D-GalN)联合内毒素(LPS)诱导的大鼠急性肝衰竭氧化应激及肝细胞凋亡的作用。方法 48只SD大鼠随机分为正常对照组、模型组、三黄茵赤汤高、中、低剂量组、双环醇组,每组8只。各组对应给药5 d,建立急性肝衰竭模型48 h后处死动物,检测血清中丙氨酸转氨酶、天门冬氨酸氨基转移酶、总胆红素,检测全血中凝血酶原时间、国际标准比率、血浆纤维蛋白原;HE染色观察肝脏病理的变化,检测肝脏组织匀浆液SOD、MDA的含量;免疫组化、免疫印迹检测肝组织caspase-3蛋白表达。结果与模型组比较,三黄茵赤汤高、中、低剂量组、双环醇组均能减少血清中丙氨酸转氨酶、天门冬氨酸氨基转移酶、总胆红素的含量、缩短全血中凝血酶原时间、国际标准比率时间,增加血浆纤维蛋白原的含量(P<0.05);明显改善肝脏组织病理变化,提高肝脏组织匀浆液SOD活性,减少MDA含量(P<0.05);下调caspase-3蛋白表达(P<0.05);三黄茵赤汤中剂量组与双环醇组无统计学差异(P>0.05),高剂量组优于双环醇组(P<0.05)。结论三黄茵赤汤防治DGalN联合LPS诱导的急性肝衰竭大鼠成量效关系,具有抗氧化的作用;三黄茵赤汤可能通过抗氧化应激抑制caspase3表达从而减少肝细胞凋亡,以达到防治大鼠急性肝衰竭的作用。
Objective To observe the effects of Sanhuangyinchi decoction （SHYCD） pretreatment on acute hepatic failure （AHF） induced by D-galactosamine and lipopolysaccharide （LPS） in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression. Methods Forty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine （700 mg/kg） plus LPS （10 μg/kg） injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase （SOD） and malondialdehyde （MDA） contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liven Results The levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased （P〈0.05） while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity （P〈0.05）, and decreased MDA levels （P〈0.05） and caspase-3 expression （P〈0.05） in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol （P〉0.05） and showed better effects at the high dose than Bicyclol （P〈0.05）. Conclusion SHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2014年第4期482-486,共5页
Journal of Southern Medical University
基金
国家自然科学基金(81173262)~~
关键词
三黄茵赤汤
急性肝衰竭
SOD
MDA
氧化应激
CASPASE-3
Sanhuangyinchi decoction
acute hepatic failure
superoxide dismutase
malondialdehyde
oxidative stress
caspase-3
