己酮可可碱预处理对硫代乙酰胺致大鼠急性肝损伤的影响

Effect of pentoxifylline pretreatment on thioacetamide-induced acute liver injury in rats

目的观察己酮可可碱预处理(pentoxifylline,PTX)对硫代乙酰胺(thioacetamide,TAA)致大鼠急性肝损伤的影响,并探讨其可能的作用机制。方法将60只SD大鼠随机分为6组:正常对照组(N),急性肝损伤模型组(M),联苯双酯[100mg/(kg·d)]阳性对照组(C),己酮可可碱低[50 mg/(kg·d)]、中[100 mg/(kg·d)]、高[200 mg/(kg·d)]剂量干预组。采取腹腔注射TAA(300 mg/kg)复制大鼠急性肝损伤模型。生化法检测血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)及肝组织内丙二醛(MDA)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)的含量变化。肝组织石蜡切片HE染色,并在光镜下观察肝脏病理改变。结果与正常组比较,模型组AST、ALT、MDA明显升高(P<0.01),SOD、GSH显著降低(P<0.01)。与模型组比较,阳性对照组及中、高剂量干预组AST、ALT、MDA显著下降(P<0.01),SOD、GSH活性提高(P<0.05);低剂量干预组AST、ALT、MDA下降,SOD、GSH升高,但差异无统计学意义(P>0.05)。HE染色结果显示阳性对照组及中、高剂量干预组大鼠肝组织病变范围与程度明显改善。结论己酮可可碱能改善硫代乙酰胺诱导的大鼠急性肝损伤,其机制可能为通过减少自由基和减轻脂质过氧化损伤,对急性肝损伤发挥保护作用。

Objective To investigate the effect and possible mechanism of pentoxifylline（ PTX） pretreatment on thioacetamide（ TAA）-induced acute liver injury in rats. Methods Sixty Sprague-Dawley rats were divided into six groups randomly： normal control group,acute liver injury model group,bifendate group,low dose [50 mg /（ kg·d） ]group,moderate dose [100 mg /（ kg·d）]group and high dose[200 mg /（ kg·d）] group. The acute liver injury model was duplicated through intraperitoneal injection of TAA（ 300 mg / kg）.The levels of alanine aminotransferase（ ALT）,aspartate transaminase（ AST） in serum and malondialdehyde（ MDA）,superoxide dismutase（ SOD）,glutathione（ GSH） in liver tissues were detected by biochemistry. The pathological changes of liver were observed under light microscope after HE staining. Results Compared with normal control group,levels of ALT,AST and MDA were significantly increased in model group（ P〈0. 01）,while contents of SOD and GSH were decreased（ P〈0. 01）. Compared with model group,levels of ALT,AST and MDA were decreased（ P〈0. 01）,while SOD and GSH were increased（ P〈0. 05） in bifendate group,moderate dose group and high dose group,but there was no significant difference from low dose group（ P〈0. 05）. HE staining showed that the range and degree of liver tissue lesions were improved obviously in bifendate group,moderate dose group and high dose group.Conclusion Pentoxifylline could improve thioacetamide-induced acute liver injury in rats possibly through reducing free radicals and lipid peroxidation damages on acute liver injury.