补骨脂对幼龄小鼠非酒精性脂肪性肝炎的影响及其机制  

Effect of psoralen corylifolia on nonalcoholic steatohepatitis in young mice and its possible mechanism

作　　者：张传香[1] 何苗 马丹凤[1] Zhang Chuanxiang;He Miao;Ma Danfeng(Department of Pharmacy,Hunan Children′s Hospital,Changsha 410007,China)

机构地区：[1]湖南省儿童医院药学部,长沙410007

出　　处：《中国医师杂志》2022年第1期90-95,共6页Journal of Chinese Physician

摘　　要：目的研究补骨脂对高脂饮食诱导小鼠非酒精性脂肪性肝炎(NASH)的保护作用及其机制。方法选取正常饲料喂养C57BL/6J小鼠后代中刚断奶的雌性小鼠,为对照组(灌胃蒸馏水);选取高脂饲料喂养小鼠的后代中雌性小鼠随机分为模型组(灌胃蒸馏水)、低剂量组[补骨脂1.125 mg/(g·d)]、高剂量组[补骨脂2.25 mg/(g·d)]和维生素E组[维生素E 0.01 mg/(g·d)],每组6只,连续喂养8周。采用全自动生化分析仪检测小鼠血清ALT、AST、TG、TC水平;HE及苦味酸-天狼猩红(SR)染色观察肝组织病理变化;二氢乙啶(DHE)荧光探针法检测肝组织活性氧(ROS)水平;试剂盒测定NADPH氧化酶的活性;Western blot检测肝组织核转录因子-κB(p65)、磷脂酰肌醇-3激酶(PI3K p85)、蛋白激酶B(Akt)及蛋白激酶C-α(PKC-α)等蛋白的表达。结果血清生化指标检测发现,模型组小鼠血清ALT、AST、TG、TC及HOMA-IR水平均高于对照组(均P<0.01)。治疗后,低、高剂量组及维生素E组血清ALT、AST、TG、TC及HOMA-IR水平均低于模型组(均P<0.05);HE及SR染色观察,模型组肝细胞肿胀,有大小不等的脂滴空泡,纤维化明显。低、高剂量组及维生素E组肝细胞脂肪变性减少,纤维化减少;且肝组织ROS和NADPH氧化酶含量均降低(均P<0.05);Western blot检测显示,模型组p-p65/p65、p-Akt/Akt、p-PKC-α/PKC-α及PI3K p85、P47phox蛋白水平较对照组升高(均P<0.01)。低、高剂量组及维生素E组p-p65/p65、p-Akt/Akt、p-PKC-α/PKC-α及PI3K p85、P47^(phox)蛋白水平下降(均P<0.01)。上述指标中,高剂量组对肝脏NASH的保护作用优于维生素E组和低剂量组(均P<0.05)。结论补骨脂能改善NASH模型小鼠肝功能,可能与抑制氧化应激、炎症反应及肝纤维化有关,这为防治儿童NASH提供了新思路。Objective To study the protective effect and possible mechanism of psoralen corylifolia on non-alcoholic steatohepatitis(NASH)induced by high-fat diet in mice.Methods The newly weaned female mice in the offspring of C57BL/6J mice fed with normal diet were selected as the control group(gavage of distilled water);the newly weaned female mice in the offspring of C57BL/6J mice fed with high-fat diet were randomly divided into model group(gavage distilled water),low-dose group[psoralen corylifolia 1.125 mg/(g·d)],high-dose group[psoralen corylifolia 2.25 mg/(g·d)]and vitamin E group[vitamin E 0.01 mg/(g·d)].Six mice in each group were fed continuously for 8 weeks.Automatic biochemical analyzer was used to detect serum alanine aminotransferase(ALT),aspartate transaminase(AST),triglyceride(TG),total cholesterol(TC)level in mice;The liver tissue pathological changes were observed by hematoxylin-eosin(HE)and Sirius-red(SR)staining;The level of reactive oxygen species(ROS)in liver tissue was detected by dihydroethidium(DHE)fluorescence probe;the activity of NADPH oxidase was detected by kit;The protein expressions of nuclear factor-κB(NF-κB),phosphatidylinositol 3 kinase(PI3K p85),protein kinase B(Akt),P47^(phox) and protein kinase C-α(PKC-α)were detected by Western blot.Western blot.Results The levels of serum ALT,AST,TG,TC and homeostasis model assessment of insulin resistance(HOMA-IR)index in the model group were higher than those in the control group(all P<0.01).After treatment,the levels of serum ALT,AST,TG,TC and HOMA-IR in low-dose group,high-dose group and vitamin E group were lower than those in model group(all P<0.05).HE and SR staining showed that hepatocytes in the model group were swollen,and there were lipid droplets of different sizes,vacuoles and obvious fibrosis.After treatment,hepatocyte steatosis and fibrosis decreased and the contents of ROS and NADPH oxidase in liver decreased(all P<0.05);Western blot showed that the p-p65/p65,p-Akt/Akt,p-PKC-α/PKC-α,PI3K,p85 and P47phox protein expression in

关 键 词：非酒精性脂肪性肝病 非酒精性脂肪性肝炎 补骨脂 肝纤维化 氧化性应激 

分 类 号：R285.5[医药卫生—中药学]