目的 研究岩黄连总碱对高糖高脂饮食诱导的代谢相关脂肪性肝病（MAFLD）小鼠的治疗作用。方法 随机取C57BL/6小鼠7只设置为对照组，喂以正常饲料；造模小鼠给予高脂饮食和高糖饮水（含20%果糖水），连续喂养10周；将造模小鼠按体质量随机分为模型组、盐酸二甲双胍（阳性药，200 mg/kg）组和岩黄连总碱低、高剂量（25、100 mg/kg）组，继续饲以高脂高糖饮食，连续ig给药5周。记录小鼠体质量，取肝脏并拍照，测定小鼠肝脏质量，计算肝脏指数；应用血糖仪测定小鼠空腹血糖（FBG）及口服糖耐量（OGTT）；试剂盒法测定血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）及游离脂肪酸（NEFA）的水平；取肝组织进行HE染色、油红O染色和Masson染色；Western blotting检测肝组织中AMP依赖的蛋白激酶（AMPK）、p-AMPK、磷脂酰肌醇3-激酶（PI3K）、p-PI3K、蛋白激酶B （Akt）、p-Akt蛋白表达情况。结果 与对照组比较，模型组小鼠体质量、肝脏指数显著升高；给药后小鼠体质量及肝脏指数显著下降（P<0.05、0.01）。与模型组比较，岩黄连总碱显著降低小鼠的FBG及OGTT水平（P<0.01）；显著降低血清TC、TG、LDL-C及NEFA水平（P<0.01）；显著改善小鼠肝组织脂肪变及纤维化；显著上调MAFLD小鼠肝组织p-AMPK、p-PI3K、p-Akt蛋白水平（P<0.01）。结论 岩黄连总碱对MAFLD发挥显著治疗作用，其作用机制可能与通过激活AMPK/PI3K/Akt信号通路，减轻肝脏脂质沉积有关。

Objective To study the effect and mechanism of Corydalis saxicola total alkaloids (CSTA) on the high-fat and high-sugar (HFHC) diet induced metabolic associated fatty liver disease (MAFLD) mice. Methods Seven C57BL/6 mice were randomly selected as control group and fed with normal diet. Mice were fed high fat diet and high sugar drinking water (containing 20% fructose water) for 10 weeks. The model mice were randomly divided into model group, metformin hydrochloride (positive drug, 200 mg/kg) group and CSTA low and high-dose (25, 100 mg/kg) groups according to body weight. Record the body weight and liver coefficient, the fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) of the mice. The total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-esterified fatty acids (NEFA) were investigated to explore weather CSTA could alleviate dyslipidemia in MAFLD mice. HE staining, oil red O staining and Masson staining of liver sections were carried out according to the manufacture's protocol. The expression of AMPK, p-AMPK, PI3K, p-PI3K, AKT, p-AKT in mouse livers were detected by Western blotting. Results The body weight and liver index of MAFLD mice were significantly increased, which were ameliorated by CSTA (P<0.05 and 0.01). Meanwhile, abnormal FBG and impaired OGTT in MAFLD mice were also normalized by CSTA (P<0.01). CSTA dramatically decreased the serum levels of TC, TG, LDL-C and NEFA in MAFLD mice (P<0.01). HFHC diet could exacerbate lipid accumulation in hepatic cells and hepatic fibrosis in mice, while these entities were relieved by CSTA. Western bloting furtherly indicated that the level of p-AMPK, p-PI3K, and p-Akt protein in the liver tissue of MAFLD mice could be upregulated by CSTA (P<0.01). Conclusion These data clarified CSTA ameliorated hepatic steatosis and dyslipidemia of MAFLD mice via a novel mechanism involved AMPK/PI3K/Akt pathway.

R285.5

“重大新药创制”科技重大专项（2017ZX09301026）