芹菜素纳米乳对肝纤维化的治疗作用

目的 研究芹菜素纳米乳对肝纤维化大鼠的治疗作用,并对其作用机制进行初步研究.方法 采用四氯化碳(CCl4)复制大鼠肝纤维化模型,90只SD大鼠经适应性饲养1周后,随机分为6组,每组15只.正常组以2 mL/kg橄榄油皮下注射;模型组以25％CCl4橄榄油为造模剂,按2 mL/kg皮下注射;治疗组分3组,在皮下注射25％CCl4橄榄油的同时灌胃给予芹菜素纳米乳25、50、100 mg/kg,1次/d;阳性对照组给予造模剂的同时给予水飞蓟宾100 mg/kg.每周造模2次(间隔2d),连续8周.末次给药后24 h,取大鼠血清和肝脏,观察芹菜素纳米乳对大鼠血清肝功能指标ALT和AST,肝纤维化指标透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PCⅢ)和肝组织中丙二醛(MDA)、羟脯氨酸(Hyp)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px),转化因子-β1(TGF-β1)、金属蛋白酶抑制因子-1(TIMP-1)、α-平滑肌肌动蛋白(α-SMA)表达的影响.结果 芹菜素纳米乳能显著降低ALT、AST、LN、PCⅢ、Ⅳ-C水平(F=13.851、6.877、5.352、7.469、20.874,P均＜0.01),升高SOD和GSH-PX活性,降低Hyp含量(F=5.470、20.734、195.76,P均＜0.01),显著降低TIMP-1、TGF-β1和α-SMA的表达(F=82.281、72.359和91.226,P＜0.01).结论 芹菜素纳米乳对CC14致肝纤维化大鼠具有一定的治疗作用,其作用机制可能与抗脂质过氧化反应、影响TGF-β1、TIMP-1、α-SMA表达有关.

Therapeutic efficacy of apigenin nanoemulsion on hepatic fibrosis

Objective To observe the therapeutic effect of apigenin nanoemulsion on fibrosis of the liver in rats,and study the mechanisms.Methods Liver fibrosis was induced in rats by CCl4 administration.Ninety SD rats were adaptively fed for 1 week and then randomly divided into 6 groups.Rats in normal group were given olive oil 2 mL/kg by subcutaneous injection;rats in model group were given 25％ CCl4 olive oil (2 mL/kg) by the same way.Rats in three treatment groups were given 25％ CC14 olive oil and added apigenin nanoemulsion (25,50,100 mg/kg) by intragastric administration each day.Rats in positive control group were given both 25 ％ CCl4 olive oil (2 mL/kg) and silybin (100 mg/kg).The 25％ CCl4 olive oil was given twice weekly (interval of 2 days) for 8 weeks.The hepatic tissue and serum were detected within 24 hours after the last administration,and the effects of apigenin nanoemulsion on the levels of hepatic function indices (ALT and AST),hepatic fibrosis indices [hyaluronic acid (HA),laminin(LN),procollagenⅢ (PC Ⅲ) and Ⅳ collagen(Ⅳ-C)],malonaldehyde(MDA),hydroxyproline (Hyp),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),transforming growth factor-β1 (TGF-β1),tissue inhibitor of metalloproteinase-1 (TIMP-1) and smooth muscle actin-α(α-SMA) were analyzed.Results Apigenin nanoemulsion could significantly reduce the levels of ALT,AST,LN,PC Ⅲ and Ⅳ-C (F=13.851,6.877,5.352,7.469,20.874,P all ＜0.01).It could increase the activity of SOD and GSH-PX,while reduce the content of Hyp (F=5.470,20.734,195.76,P all＜0.01),and reduce the expressions of TIMP-1,TGF-β31 and α-SMA (F=82.281,72.359,91.226,P all＜0.01).Conclusions Apigenin nanoemulsion reduces CC14-induced hepatic fibrosis in rats.Its mechanism may relate to the inhibition of lipid peroxidation reaction and the regulation of TGF-β1,TIMP-1 and α-SMA expression.