摘要
目的探讨扶正化瘀方提取物对大鼠脂肪性肝炎与肝纤维化的作用。方法以CCl4皮下注射加高脂低蛋白饮食复合因素造模3￣6w,药物组自造模之日起,给与10ml/kg大鼠体重的扶正化瘀方提取液,相当于含生药扶正化瘀方1.5g/kg,每日1次,分别灌胃3w和6w。观察肝组织脂肪变性与炎症变化、胶原沉积;测定血清肝功能和血清甘油三酯(TG)、总胆固醇(TC)含量;肝组织匀浆测定TG、TC、丙二醛(MDA)、谷胱甘肽(GSH)含量与超氧化物歧化酶(SOD)、γ-谷氨酰转肽酶(GGT)活性、羟脯氨酸(Hyp)含量;免疫组织化学染色与western印迹法观察α-平滑肌肌动蛋白(α-SMA)的表达部位与水平。结果扶正化瘀方提取物用药3w可改善模型大鼠肝组织脂肪变性与炎症;血清TBil含量,模型大鼠为(33.8±14.5)μmol/L,药物组为(24.1±12.5)μmol/L(P<0.05);血清白蛋白含量模型大鼠为(25.9±0.7)g/L,药物组为(28.3±1.5)g/L(P<0.05)。降低模型肝组织Hyp、TG与MDA含量(P<0.05),提高SOD活性(P<0.05)。扶正化瘀方提取物用药6w可减轻模型大鼠肝纤维化;降低血清ALT、AST水平(P<0.05);降低肝组织Hyp、TG与MDA含量和GGT活性(P<0.05),提高SOD活性。扶正化瘀方提取物用药3w与6w均可明显减少模型大鼠肝组织的α-SMA高表达(P<0.05),且6w作用较3w更为明显。结论扶正化瘀方提取物可显著改善大鼠脂肪性肝炎、抑制脂肪性肝纤维化,其作用机制与抗肝组织脂质过氧化、抑制肝星状细胞活化有关。
Objective To explore the effects of Fuzheng Huayu Decoction on steatohepatitis and liver fibrosis in rats. Methods The rat models with steatohepatitis and liver fibrosis were induced by injection of carbon tetrachloride （CCl4） subcutaneously and fed with high lipid and low protein diet. For the drug treated groups,rats were administered with Fuzheng Huayu Decoction with a dosage of lOml/kg body weight （equal to Fuzheng Huayu Decoction 1.5g/kg body weight） by garage from the intoxication start,once a day,and last for 3w or 6w respectively. Hepatic inflammation and fatty degeneration were stained with HE and Oil red O stain,collagen deposition with Sirius red. The liver function parameters including serum ALT, AST activity, Alb and total bilirubin levels, and serum contents of TG and TC were determined. The hepatic lipid peroxidation parameters including TG, SOD, MDA, GGT and GSH were also measured. Hepatic hydroxyproline （Hyp） content was detected with Jamall＇ method. The expression of α-SMA was analyzed by Western blotting and immunehistopathological staining. Results While Fuzheng Huayu Decoction 3w treated group showed slighter hepatic inflammation and fatty degeneration, and lower total bilirubin levels and Hyp, TG and MDA content, and higher Alb content and SOD activity than those in 3w model group. The 6w treated group showed slighter fibrosis, lower Hyp, TG and MDA content and GGT activity and higher SOD activity than those in the 6w model. The 3w and 6w treated groups showed less α-SMA expression than that in the model, especially in the treated group 6w. Conclusion Fuzheng Huayu Decoction has a good effect against steatohepatitis and fatty hepatic fibrosis, which may be related to the prevention from lipid peroxidation in fibrotic livers and inhibition of hepatic stellate cells activation.
出处
《药品评价》
CAS
2007年第6期414-418,共5页
Drug Evaluation
基金
上海市科委重点基础项目(04JC14069)
教育部新世纪优秀人才资助计划(NCET-04-0437)
上海市教育委员会E-研究院建设计划(E03008)
上海市重点学科建设项目(Y0302)部分资助。
