2020 年第 7 期 第 15 卷

姜黄素脂质体对高脂诱导的非酒精性脂肪性肝病小鼠的降脂保肝作用

Effect of curcumin liposomes on lipid-lowering and hepatoprotective effects of hyperlipidemia-induced nonalcoholic fatty liver disease mice

作者：李辉1刘志虎1李华2卿笃信3

英文作者：Li Hui1 Liu Zhihu1 Li Hua2 Qing Duxin3 

单位：1河北省邢台市人民医院肝胆外科054000；2河北省邢台市人民医院胃肠肿瘤外科054000；3中南大学湘雅二医院消化内科，长沙410083

英文单位：1Department of Hepatobiliary Surgery Xingtai People′s Hospital Hebei Province Xingtai 054000 China； 2Department of Gastrointestinal Oncology Surgery Xingtai People′s Hospital Hebei Province Xingtai 054000 China； 3Department of Gastroenterology the Second Xiangya Hospital of Central South University Changsha 410083 China

关键词：非酒精性脂肪性肝病；姜黄素；脂质体；脂肪；三酰甘油

英文关键词：Non-alcoholicfattyliverdisease；Curcumin；Liposome；Fat；Triglyceride

• 摘要：

• 目的研究姜黄素脂质体对高脂诱导的非酒精性脂肪性肝病（NAFLD）小鼠的降脂保肝作用。方法通过体外脂肪乳诱导LO2人正常肝细胞建立NAFLD细胞模型，测定细胞内三酰甘油水平变化。选取C57BL/6小鼠32只，随机分为空白对照组、模型对照组、姜黄素混悬液组（30 mg/kg）和姜黄素脂质体组（30 mg/kg），每组8只。空白对照组喂食普通饲料和纯净水，其余3组喂食高脂饲料，诱导建立NAFLD小鼠模型，12周后进行给药处理，给药方式为灌胃给药，每2天给药1次。持续给药8周后测定小鼠血清中总胆固醇、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的含量，同时测定小鼠肝脏系数并对其肝脏和腹部脂肪组织做苏木精-伊红染色观察其病理学变化。结果通过检测LO2人正常肝细胞内的三酰甘油含量发现，经过姜黄素脂质体干预的高剂量观察组、低剂量观察组细胞内三酰甘油含量均低于姜黄素混悬液组（均P<0.05）。动物模型实验中，模型对照组小鼠血清总胆固醇、LDL和肝脏系数高于空白对照组，HDL低于空白对照组；姜黄素混悬液组总胆固醇、肝脏系数低于模型对照组；姜黄素脂质体组总胆固醇、LDL、肝脏系数低于姜黄素混悬液组，HDL高于姜黄素混悬液组［（2.57±0.19）mmol/L比（3.24±0.21）mmol/L、（1.05±0.31）mmol/L比（1.58±0.14）mmol/L、（2.58±0.17）比（3.14±0.23）、（3.14±0.27）mmol/L比（2.58±0.35）mmol/L］，差异均有统计学意义（P<0.01或P<0.05）。组织病理学切片显示，通过姜黄素干预治疗后，腹部脂肪细胞不同程度减小；与姜黄素混悬液组相比，姜黄素脂质体组小鼠的腹部脂肪细胞更小，相同视野面积下能观测到更多的细胞。模型对照组小鼠肝脏组织与空白对照组相比出现脂肪变性，细胞质模糊，有脂质空泡出现，而空白对照组则肝脏组织结构完整，肝细胞排列规则，细胞核形态正常，通过药物干预后，姜黄素混悬液组和姜黄素脂质体组肝细胞内脂滴空泡样减少，细胞形态结构趋于完善，脂肪样病变减少。结论姜黄素脂质体对NAFLD小鼠有较好的降脂保肝作用。

• ObjectiveTo study the Lipid-lowering and liver-protective effects of curcumin liposome on high fat-induced non-alcoholic fatty liver disease(NAFLD) mice. Methods The normal human hepatocytes LO2 of NAFLD cell model was established by in vitro fat milk induction, and the intracellular triglyceride level was measured. Thirty-two C57BL/6 mice were randomly divided into blank control group, model control group, curcumin suspension group(30 mg/kg) and curcumin liposome group(30 mg/kg). The blank control group was fed with ordinary feed and purified water, and the other three groups were fed with high-fat feed, established the NAFLD mouse model, which was administered after 12 weeks. The model of administration was intragastric administration and was administered once every two days. After 8 weeks of continuous administration, the contents of total cholesterol(TC), low density lipoprotein (LDL) and high density lipoprotein(HDL) in the serum of the mice were determined, and the liver coefficient of the mice was measured and hematoxylin eosin staining was performed on the liver and abdominal fat. The pathological changes were examined by staining. Results  By detecting the content of triacylglycerol in normal human hepatocytes LO2, it was found that the content of triacylglycerol in high-dose and low-dose observation groups was lower than that in curcumin suspension group(both P<0.05). In the animal model experiment, the TC, LDL and liver coefficient in the model group were higher and HDL was lower than those in the blank control group； the TC and liver coefficient of curcumin suspension group were lower than those of model control group； the TC, LDL and liver coefficient of curcumin liposome group were lower and HDL was higher than that of curcumin suspension group［（2.57±0.19）mmol/L vs （3.24±0.21）mmol/L, （1.05±0.31）mmol/L vs （1.58±0.14）mmol/L, （2.58±0.17） vs （3.14±0.23）, （3.14±0.27）mmol/L vs （2.58±0.35）mmol/L］（P<0.01 or P<0.05）. Histopathological sections showed that, after curcumin intervention, the size of abdominal fat cells decreased in varying degrees； compared with curcumin suspension group, the abdominal fat of mice in curcumin liposome group was smaller, and more cells could be observed under the same visual field area. The liver tissue of the model control group mice showed fatty degeneration compared with the blank control group, the cytoplasm was blurred, and lipid vacuoles appeared. In the blank group, the liver tissue structure was intact, the liver cells were arranged regularly, and the nucleus morphology was normal. After drug intervention, the number of lipid droplets and vacuoles in hepatocytes of curcumin suspension group and curcumin liposome group decreased, the morphological structure of hepatocytes tended to be improved, and the number of fatty lesions decreased. Conclusion Curcumin liposome has good lipid-lowering and liver-protective effect on NAFLD mice.