大鼠酒精性肝损伤模型的建立

目的:建立大鼠酒精性肝损伤模型,为进一步研究药物对肝损伤的保护机制奠定实验基础。方法:将70只SD大鼠随机分为5组,分别为阴性对照组(生理盐水),1周白酒胃灌注模型组(1周组),2周白酒胃灌注模型组(2周组),4周白酒胃灌注模型组(3周组)和8周白酒胃灌注模型组(4周组)。阴性对照组胃灌注生理盐水3d,1周组、2周组、4周组和8周组分别给于白酒胃灌注1周、2周、4周和8周。实验结束后,收集肝脏标本进行病理组织学检查,检测血清中丙氨酸转氨酶ALT、AST、TG活性及肝组织中SOD活性、MDA含量。结果:与阴性对照组比较,2周组ALT活性(89.73±15.06)高于阴性对照组(78.59±11.62)升高(89.73±15.06 vs.78.59±11.62,P<0.05)外,模型1周和2周组ALT、AST和TG活性无明显差异;模型8周组AST和TG活性升高(166.49±15.73 vs.154.07±9.38;0.93±0.21 vs.0.71±0.19;均P<0.05),而ALT活性显著上升(112.36±9.84 vs.78.59±11.62,P<0.01)。与空白组比较,模型1周和2周组SOD活性和MDA含量无明显差异;模型4周组SOD活性显著下降(98.41±12.60 vs.127.52±13.09,P<0.01),而MDA含量升高(6.05±1.47 vs.4.62±1.24,P<0.05);模型8周组SOD活性降低(109.76±23.05 vs.127.52±13.09,P<0.05),而MDA含量无变化。显微镜下显示,4周组大鼠出现明显的脂肪变性,而8周组大鼠则出现典型的酒精性肝纤维化表现。结论:采用酒精浓度为45%的白酒灌胃,观察到大鼠不同时期酒精性肝损伤的改变,可将该模型运用于护肝药物对大鼠酒精性肝损伤保护作用的研究。

Establishment of alcohol-induced liver injury model in rats

Objective: To establish alcohol-induced liver injury model in rats and lay foundation for further study on mechanism of drug protecting alcoholic liver injury.Methods: Seventy Sprague-Dawley rats were randomly divided into one control group and four model groups.Model groups were given 45% diluted alcohol 10 mL/kg per day by gavage for 1(model group 1),2(model group 2),4(model group 3),and 8 weeks(model group 4),respectively.The control group was given distilled water by gavage for 3 days.Rats were sacrificed,livers extracted for pathological observation.The activity of alanine transarninase(ALT),aspartate transarninase(AST),triglyceride(TG) in serum and the activity or content of superoxide dismutase(SOD) and malondialdehyde(MDA) in liver were measured.Results: Compared with the control group,the serum ALT,AST and TG were not significantly changed in the model group 1 and 2,but the serum ALT was significant higher in model group 2 than that in the control group(89.73±15.06 vs.78.59±11.62,P<0.05).The serum AST and TG were increased(166.49±15.73 vs.154.07±9.38;0.93±0.21 vs.0.71±0.19,P all <0.05) ALT activity also significantly inreased(112.36±9.84 vs.78.59±11.62) in model group 4.Compared with the control group,the activity of SOD and the content of MDA were not significantly changed in model group 1 and 2;but the activity of SOD in model group 3 was significantly decreased(98.41 ±12.60 vs.127.52±13.09,P<0.01),content of MDA was increased(6.05±1.47 vs.4.62±1.24,P<0.05).The activity of SOD was decreased(109.76±23.05 vs.127.52±13.09,P<0.05),but the content of MDA was not changed in model group 4.Under microscope,obvious fatty degeneration was observed in model group 3 and typical alcoholic liver fibrosis was obvious in model group 4.Conclusion: The alcoholic liver injury of different stages were induced by 45% diluted alcohol by gavage,which could be applied in study of mechanism of drug protecting alcoholic liver injury in rats.