大蒜素联合非诺贝特治疗混合性高脂血症大鼠的疗效及对肝功能的影响

Effect of combination therapy with allicin and fenofibrate on liver function in rats with combined hyperlipidemia

目的探讨长期服用大蒜素联合非诺贝特治疗混合性高脂血症的疗效及对肝功能的影响。方法将雄性Wistar大鼠60只,随机分为正常对照组、模型组、非诺贝特组[80 mg/(kg.d)]、大蒜素组[60 mg/(kg.d)]和联合用药组[大蒜素20 mg/(kg.d)+非诺贝特30 mg/(kg.d)]。复制模型4周,证实模型成功后用药干预8周。实验第12周末,腹主动脉取血分别检测血脂、血清ALT和AST水平,并做肝脏组织形态学检查。结果 (1)与正常对照组相比,其余各组血清TC、TG、LDL-C及HDL-C水平均明显增高(P<0.01);与模型组相比,各用药组血清TC、TG及LDL-C水平均明显降低(P<0.01),而非诺贝特组和联合用药组血清HDL-C水平明显增高(P<0.05)。(2)与正常对照组相比,其余各组血清ALT及AST水平均明显增高(P<0.01或P<0.05);与模型组相比,各用药组血清ALT及AST均明显降低(P<0.01);与非诺贝特组相比,大蒜素组和联合用药组血清ALT及AST均明显降低(P<0.01)。(3)肝脏组织形态学检查发现,模型组发生重度肝细胞脂肪变性,各用药组肝细胞脂肪变性均有不同程度减轻,但非诺贝特组可见肝细胞点状坏死,胆小管扩张。结论大蒜素联合非诺贝特治疗大鼠混合性高脂血症,其疗效与单纯应用加倍剂量的非诺贝特相当,但对肝脏损害较小。

Objective： To study the effect of combination therapy with allicin and fenofibrate on mixed hyperlipidemia and hepatic function.Methods： Sixty male Wistar rats were randomized into the five groups： the control group,the model group,the fenofibrate group[fenofibrate 80mg/（kg·d）],the allicin group[allicin 60mg/（kg·d） ]and the combination therapy group[allicin 20mg/（kg·d） ＋fenofibrate 30mg/（kg·d）].The experiment was conducted after 1 week of adaptive feeding.After the rat model of mixed hyperlipidemia was established by 4 weeks of high fat diet and 8 weeks of medicine treatment,the levels of TC,TG,LDL-C,HDL-C,ALT and AST in the serum were measured,and the morphologic changes of liver tissue were observed.Results：（1） Compared with the control group,the levels of TC,TG,LDL-C and HDL-C in all the other groups were significantly higher（P〈0.01）;Compared with the model group,the levels of TC,TG and LDL-C in all groups with medicine treatment showed a significant decrease（P〈0.01）,but the levels of HDL-C were remarkably higher in the fenofibrate group and the combination therapy group（P〈0.05）.（2） Compared with the control group,the levels of ALT and AST in all the other groups showed a significant increase（P〈0.01 or P〈0.05）;Compared with the model group,serum ALT and AST levels of rats in all groups with medicine treatment showed a significant decrease（P〈0.01）;Compared with the Fenofibrate group,the serum ALT and AST levels of rats in both the allicin group and the combination therapy group showed a significant decrease（P〈0.01）.（3） The liver histological examination revealed that severe fatty degeneration of liver cells occurred in the model group,the steatosis of liver cells in the medicine treated group were significantly ameliorated,but the fenofibrate group showed spotty necrosis of liver cells and bile duct expansion.Conclusion： The effect of long-term combination therapy with allicin and fenofibrate on mixed hyperlipidemia is similar to that of single chemotherapy of doubling dose of fenofibrate,but the former one has decreased side effects on liver.