咖啡酸苯乙酯对实验性肝损伤大鼠的保护作用

Protective effect of caffeic acid phenethyl ester on liver damage in rats

目的探讨不同给药途径及不同剂量咖啡酸苯乙酯(CAPE)对四氯化碳(CCl_4)等复合因素诱导大鼠肝损伤的保护作用。方法选取95只雄性SD大鼠,随机分为9组,A:正常对照组;B:溶剂对照组,皮下注射橄榄油,腹腔注射10%乙醇;C:单纯模型组,腹腔注射10%乙醇;D:维生素E组,腹腔注射维生素E 10mg/kg,1次/d;E～I:CAPE(10%乙醇溶液)干预组:腹腔注射3 mg/kg、6 mg/kg和1 2 mg/kg,1次/d;灌胃12 mg/kg和24 mg/kg,1次/d。C～I组均予以40%CCl_4橄榄油溶液皮下注射、30%乙醇灌胃以及高脂饲料作为单一饲料,同时给予对应药物干预。共10周。末次染毒48 h后处死大鼠,采血并计算肝、脾和双肾系数。检测血清TBil、ALT、AST等肝功能指标。肝组织行常规HE染色。结果 CAPE各剂量组与单纯模型组相比,大鼠血清TBil、ALT和AST水平均有不同程度降低,且随CAPE剂量增大,TBil水平降低越明显;其中CAPE(12 mg/kg腹腔注射和24 mg/kg灌胃)两个组效果最好,其TBil水平与正常对照组对比,差异无统计学意义(P>0.05)。CAPE不同给药方式比较显示,在本课题选择的剂量范围内,CAPE腹腔注射组的ALT及AST水平下降明显,好于灌胃组,CAPE(12 mg/kg腹腔注射)组与灌胃两个剂量组分别比较,P值均小于0.05。结论 CAPE经腹腔注射或灌胃途径给药均可不同程度改善CCl_4复合因素所致肝损伤,且优于维生素E组。经比较不同给药方式的效果发现,在所观察的剂量范围内,CAPE经腹腔注射的保肝作用较灌胃给药好,同时在3～12 mg/kg剂量范围内呈剂量依赖性。

Objective To evaluate the protective effects of different doses of caffeic acid phenethyl ester （CAPE）, which was given by intraperitoneal injection and oral route respectively, in rats with liver damage. Methods Ninety-five Sprague-Dawley male rats were randomly divided into nine groups as follows： normal group, solvent control group, model group, the drug groups treated with VitE （10 mg/kg, i.p. once a day） and CAPE （3 mg/kg, 6 mg/kg, 12 rag/ kg, i.p. once a day; 12 mg/kg and 24 mg/kg, i.g. once a day） throughout 10 weeks. All groups received administration with CC14 （via s.c. injection）, alcohol and high-lipid forage, except normal group and solvent control group. At the end of the treatment, liver, kidneys and spleen were weighed, as well as total bilirubin （TBil）, aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels in serum were quantified. Liver tissue was taken out to undergo HE staining. Results Compared to model group, the rats treated with CAPE showed significant decrease in TBil, ALT and AST levels （P^0.05）. And TBil w＇as decreased by CAPE in a dose-dependent manner. Additionally, we compared the effects of CAPE by intraperitoneal injection with oral administration, and found that ALT and AST levels in the CAPE group by intraperitoneal injection at the dose of 12 mg/kg were markedly lower than that in both dose （12 mg/kg and 24 mg/kg, i. g. ） groups administrated orally（P〈0.05）. Conclusion The results demonstrated within the dose range used in this experiment, CAPE had protective effect on liver damage with the preference to intraperitoneal injection and in a dose-dependent manner.