目的 研究巖黃連總堿對(duì)高糖高脂飲食誘導(dǎo)的代謝相關(guān)脂肪性肝病（MAFLD）小鼠的治療作用。方法 隨機(jī)取C57BL/6小鼠7只設(shè)置為對(duì)照組，喂以正常飼料；造模小鼠給予高脂飲食和高糖飲水（含20%果糖水），連續(xù)喂養(yǎng)10周；將造模小鼠按體質(zhì)量隨機(jī)分為模型組、鹽酸二甲雙胍（陽性藥，200 mg/kg）組和巖黃連總堿低、高劑量（25、100 mg/kg）組，繼續(xù)飼以高脂高糖飲食，連續(xù)ig給藥5周。記錄小鼠體質(zhì)量，取肝臟并拍照，測(cè)定小鼠肝臟質(zhì)量，計(jì)算肝臟指數(shù)；應(yīng)用血糖儀測(cè)定小鼠空腹血糖（FBG）及口服糖耐量（OGTT）；試劑盒法測(cè)定血清總膽固醇（TC）、三酰甘油（TG）、低密度脂蛋白膽固醇（LDL-C）、高密度脂蛋白膽固醇（HDL-C）及游離脂肪酸（NEFA）的水平；取肝組織進(jìn)行HE染色、油紅O染色和Masson染色；Western blotting檢測(cè)肝組織中AMP依賴的蛋白激酶（AMPK）、p-AMPK、磷脂酰肌醇3-激酶（PI3K）、p-PI3K、蛋白激酶B （Akt）、p-Akt蛋白表達(dá)情況。結(jié)果 與對(duì)照組比較，模型組小鼠體質(zhì)量、肝臟指數(shù)顯著升高；給藥后小鼠體質(zhì)量及肝臟指數(shù)顯著下降（P<0.05、0.01）。與模型組比較，巖黃連總堿顯著降低小鼠的FBG及OGTT水平（P<0.01）；顯著降低血清TC、TG、LDL-C及NEFA水平（P<0.01）；顯著改善小鼠肝組織脂肪變及纖維化；顯著上調(diào)MAFLD小鼠肝組織p-AMPK、p-PI3K、p-Akt蛋白水平（P<0.01）。結(jié)論 巖黃連總堿對(duì)MAFLD發(fā)揮顯著治療作用，其作用機(jī)制可能與通過激活A(yù)MPK/PI3K/Akt信號(hào)通路，減輕肝臟脂質(zhì)沉積有關(guān)。

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

“重大新藥創(chuàng)制”科技重大專項(xiàng)（2017ZX09301026）