不同剂量维生素C预防和治疗非酒精性脂肪性肝病小鼠的疗效分析  

The efficacy of different doses of vitamin C in prevention and treatment of non-alcoholic fatty liver disease in mice

作　　者：曾庆敏 赵黎莉[2] 智登科 王恺[3] 孔德领[3] 李嘉[2] Zeng Qingmin;Zhao Lili;Zhi Dengke;Wang Kai;Kong Deling;Li Jia

机构地区：[1]天津医科大学研究生院,300070 [2]天津市第二人民医院肝病科药物化学生物学国家重点实验室(南开大学)天津市肝病医学研究所,300192 [3]南开大学生命科学学院,天津300071

出　　处：《中华消化杂志》2020年第2期115-121,共7页Chinese Journal of Digestion

基　　金：药物化学生物学国家重点实验室(南开大学)2018年开放基金资助课题(2018116)。

摘　　要：目的探讨不同剂量维生素C预防和治疗非酒精性脂肪性肝病(NAFLD)小鼠的疗效。方法C57BL/6小鼠予高脂饮食建立NAFLD模型。实验分为早期预防和后期治疗,均分别设置对照组、高脂组、低剂量(15 mg·kg^-1·d^-1)维生素C(LD-VC)组、中剂量(30 mg·kg^-1·d^-1)维生素C(MD-VC)组和高剂量(90 mg·kg^-1·d^-1)维生素C(HD-VC)组5个亚组,每组6只。早期预防是在造模同时给予维生素C预防12周,后期治疗是在高脂饲养6周时通过肝脏病理确定NAFLD建模成功后再给予不同剂量维生素C治疗12周。观察各组间小鼠体质量、肾周脂肪重,血清ALT、AST、总胆固醇、三酰甘油水平的差异;同时采用非酒精性脂肪性肝病活动度积分(NAS)系统对各组小鼠肝组织病理学进行肝细胞脂肪变性、小叶内炎症和气球样变评分。统计学分析采用Tukey′s多重比较检验和Kruskat Wallis H检验。结果早期预防中,LD-VC组的体质量、肾周脂肪重、三酰甘油水平和肝细胞脂肪变性评分均低于高脂组[(30.27±0.94)g比(32.18±1.35)g、(0.25±0.05)g比(0.32±0.02)g、(0.25±0.02)mmol/L比(0.30±0.03)mmol/L、0分比1.0(1.0)分];MD-VC组的体质量、肾周脂肪重、血糖水平、三酰甘油水平和肝细胞脂肪变性评分均低于高脂组[(29.72±0.58)g比(32.18±1.35)g、(0.24±0.05)g比(0.32±0.02)g、(6.93±0.59)mmol/L比(8.33±1.02)mmol/L、(0.24±0.04)mmol/L比(0.30±0.03)mmol/L、0分比1.0(1.0)分];HD-VC组的血糖和三酰甘油水平均低于高脂组[(6.72±0.59)mmol/L比(8.33±1.02)mmol/L、(0.23±0.04)mmol/L比(0.30±0.03)mmol/L],差异均有统计学意义(P均<0.05)。后期治疗LD-VC组的三酰甘油水平低于高脂组[(0.25±0.07)mmol/L比(0.37±0.06)mmol/L];MD-VC组的体质量、肾周脂肪重、血糖水平、三酰甘油水平、肝细胞脂肪变性评分均低于高脂组[(29.93±1.28)g比(33.24±2.45)g、(0.29±0.08)g比(0.53±0.14)g、(7.63±0.57)mmol/L比(9.13±1.52)mmol/L、(0.23±0.03)mmol/L比(0.37±0.06)mmol/LObjective To investigate the efficacy of different doses of vitamin C(VC)in prevention and treatment of non-alcoholic fatty liver disease(NAFLD)in mice.Methods C57BL/6 mice were fed with high-fat diet to establish NAFLD models.The experimental animals were divided into early prevention and later treatment groups.Both of these two experimental processes had five subgroups,including control,high-fat diet(HFD),low-dose vitamin C(LD-VC,15 mg/kg per day),medium-dose vitamin C(MD-VC,30 mg/kg per day)and high-dose vitamin C(HD-VC,90 mg/kg per day)subgroup,with six mice in each subgroup.In the early prevention group,the mice were prophylactically received VC for 12 weeks.In the later treatment group,the mice were treated with different dose of VC for 12 weeks after fed with HFD for six weeks and confirmed NAFLD by liver pathology.The differences in body weight,perirenal adipose tissue mass and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),and triacylglycerol(TG)were observed among different groups.The scores of hepatocyte steatosis,lobular inflammation and ballooning in liver histopathology of mice in each group were evaluated by non-alcoholic fatty liver disease activity score(NAS)scoring system.Tukey′s multiple comparison test and Kruskal-Wallis H test were performed for statistical analysis.Results In the early prevention group,the body weight,perirenal adipose tissue mass,TG level and the score of liver steatosis of LD-VC subgroup were all lower than those of HFD subgroup((30.27±0.94)g vs.(32.18±1.35)g,(0.25±0.05)g vs.(0.32±0.02)g,(0.25±0.02)mmol/L vs.(0.30±0.03)mmol/L,0 vs.1.0(1.0)).The body weight,perirenal adipose tissue mass,blood glucose level,TG level and score of liver steatosis of MD-VC subgroup were all lower than those of HFD subgroup((29.72±0.58)g vs.(32.18±1.35)g,(0.24±0.05)g vs.(0.32±0.02)g,(6.93±0.59)mmol/L vs.(8.33±1.02)mmol/L,(0.24±0.04)mmol/L vs.(0.30±0.03)mmol/L,0 vs.1.0(1.0));meanwhile,the blood glucose level and TG level of HD-V

关 键 词：非酒精性脂肪性肝病 维生素C 预防 治疗 小鼠 

分 类 号：R575[医药卫生—消化系统]