桦木酸对酒精性肝损伤小鼠线粒体凋亡通路的影响

EFFECT OF BETULINIC ACID ON MITOCHONDRIAL APOPTOTIC PATHWAY IN MICE WITH LIVER INJURY INDUCED BY ETHANOL

目的研究桦木酸(betulinic acid,BA)对酒精性肝损伤小鼠线粒体信号通路的影响。方法 56只健康雄性小鼠随机分为8组,即正常对照组(NC),酒精模型组(MC),BA低、中、高剂量组(L-BA,M-BA, H-BA,按0.25、0.5、1 mg/kg bw给与),BA低、中、高剂量与酒精联合组(L-BAA, M-BAA, H-BAA)。NC、MC组灌胃1%的可溶性淀粉,其余各组灌胃混悬于可溶性淀粉中不同剂量的BA,1/d,连续14d后,除NC组,L-BA,M-BA,H-BA组灌胃生理盐水外,其余4组均按10 ml/kg灌胃50%酒精诱发酒精性肝损伤模型。检测血清细胞色素P450 2E1(CYP2E1)水平,采用Western blot检测肝脏线粒体信号通路中Bcl-2、Bax、Caspase-9和Caspase-3蛋白表达的变化。结果 BA预处理后,抑制由酒精引起的CYP2E1水平升高,显著降低酒精致肝损伤小鼠Bax/Bcl-2比值,明显减少Caspase-9和Caspase-3蛋白表达量,且呈量效关系。结论说明BA对酒精诱导肝损伤有预防性的保护作用,这种保护作用可能与调控线粒体凋亡通路有关。

Objective To investigate the effect of betulinic acid(BA) on mitochondrial apoptotic pathway in mice with liver injury induced by ethanol. Methods 56 healthy male mice were randomly divided into 8 groups: normal control group(NC), model control group(MC), low-dosage, medium-dosage and high-dosage BA groups(L-BA, M-BA and H-BA, 0.25, 0.5, 1.0 mg/kg bw), low-dosage, medium-dosage and high-dosage BA with alcohol groups(L-BAA, M-BAA and H-BAA). The mice in the NC and MC groups were administered orally with 1% starch and the those in other groups were administered orally with different doses of BA daily for 14 days. The model of liver injury was induced by orally administrating 50% ethanol at the dosage of 10 ml/kg bw in MC, L-BAA, M-BAA, and H-BAA groups, while other groups were treated with saline. The level of cytochrome P4502E1(CYP2E1) in serum was measured. The protein expressions of Bcl-2, Bax, Caspase-9 and Caspase-3 in mitochondrial signal pathway of the liver were detected by Western blot. ResultsPretreatment with BA significantly reduced the level of serum CYP2E1 in mice exposed to ethanol. The protein expressions of Caspase-9 and Caspase-3, and the ratio of Bax/Bcl-2 were decreased remarkably after BA pretreatment in ethanol treated groups in a dose-dependent manner. Conclusion These findings reveal a potential protective capability of BA against ethanol-induced liver injury through regulating mitochondrial apoptotic pathway.