甘草酸配伍蛇床子素对大鼠酒精性脂肪肝的治疗作用

Therapeutic Compatibility Effect of Glycyrrhizin and Osthole on the Treatment of Alcoholic Fatty Liver in Rats

  • 摘要: 目的 研究甘草酸配伍蛇床子素对大鼠酒精性脂肪肝的治疗影响,初步探讨组分配伍的作用机制。方法 建立大鼠酒精性脂肪肝模型后,随机分为正常组、模型组、阳性药(力平之)组、蛇床子素组(Ost)、甘草酸组(GL)、蛇床子素与甘草酸配伍高、中、低剂量组。治疗组从实验第5周起,分别给予药物灌胃:阳性药组ig力平之20 mg/(kg·d),蛇床子素组10 mg/(kg·d) ig,甘草酸组22.5 mg/(kg·d) ig,配伍低剂量组为ig蛇床子素5 mg/(kg·d)和甘草酸11.25 mg/(kg·d),配伍中剂量组为ig蛇床子素10 mg/(kg·d)和甘草酸22.5 mg/(kg·d),配伍高剂量组为ig蛇床子素20 mg/(kg·d)和甘草酸45 mg/(kg·d),正常组和模型组灌胃等体积的生理盐水连续灌胃6周。末次给药后,观察大鼠一般情况;光镜观察肝脏的病理变化,同时分别测定大鼠血清门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)、谷丙转氨酶(ALT)水平以及肝组织匀浆中总胆固醇(TC)、甘油三酯(TG)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量;Western blot法检测大鼠肝组织PPARα蛋白的表达情况。结果 各治疗组与模型组比较,肝组织病理变化有不同程度的改善;甘草酸配伍蛇床子素中剂量和高剂量组能显著降低血清ALT、AST和AKP水平(P<0.05);大鼠肝组织药理活性测试结果显示配伍中剂量和高剂量组能显著降低肝组织MDA含量,提高SOD的活性,差异具有统计学意义(P<0.01),配伍中剂量组能显著降低大鼠肝脏TG和TC含量(P<0.05);Western blot结果表明,各治疗组PPARα蛋白水平与模型组相比有不同程度上调,而配伍中剂量和高剂量组肝组织中PPARα蛋白水平表达量显著上调,具有统计学意义(P<0.01)。结论 甘草酸与蛇床子素合理的组分配伍能协同治疗酒精性脂肪肝,可能通过配伍改善肝脏功能、调节脂肪代谢、抗脂质氧化作用和增加PPARα蛋白的表达,促使损伤的肝组织得以修复。

     

    Abstract: OBJECTIVE To study the effect of glycyrrhizin acid and osthole on the treatment of alcoholic fatty liver in rats, and to explore the mechanism of compatibility of components. METHODS After the establishment of rat alcoholic fatty liver, the rats were randomly divided into normal group, model group, positive drug group (Lipingzhi), osthole (Ost) group, glycyrrhizic acid (GL) group, high dose group of osthole and glycyrrhizic acid, medium dose group of osthole and glycyrrhizic acid and low dose group of osthole and glycyrrhizic acid. The treatment groups were given by gastrogavage every day starting from the 5th week, the positive group ig. Lipingzhi 20 mg/(kg·d), the osthole group ig. Ost 10 mg/(kg·d), the glycyrrhizic acid group ig. GL 22.5 mg/( kg·d), the low dose group ig. the compatibility components of Ost 5 mg/(kg·d) and GL 11.25 mg/(kg·d), the medium dose group ig. Ost 10 mg/(kg·d) and GL 22.5 mg/(kg·d), the high dose group ig. Ost 20 mg/(kg·d) and GL 45 mg/(kg·d) and the normal and model group were given distilled water with equal volume for 6 weeks. We observed the sign of rats, the pathological changes of liver with the optical microscope. Then we measured AST, AKP and ALT changes in rat serum and TC, TG, SOD and MDA contents in liver homogenate. The expression of PPARα protein in liver tissue was examined using Western blot method. RESULTS Compared with the model group, the pathological changes of liver tissue were improved in different treatment groups and the ALT, AST and AKP levels in serum were significantly decreased in the groups of glycyrrhizin combined with osthole at medium and high doses(P<0.05). The liver tissue of rats test results showed the medium dose and high dose groups of glycyrrhizin combined with osthole could significantly reduce the content of MDA and improve the activity of SOD. There were significant differences among the model group and the treatment groups at medium and high doses (P<0.01). The TG and TC levels in the group of glycyrrhizin combined with osthole in medium dose were lower than the model group(P<0.05). Western blot results showed that the PPARα protein levels in treatment groups compared with the model group had a different degree of increase, and the compatibility of medium dose and high-dose groups in the liver tissue of PPARα protein expression was up-regulated with statistical significance (P<0.01). CONCLUSION The reasonable combination of glycyrrhizic acid and osthole had synergistic treatment on alcoholic fatty liver, and its main mechanism might be related to the improving of liver function, regulation of fat metabolism, anti-lipid oxidation and the increased protein expression of PPARα.

     

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