丹皮酚对高脂血症大鼠肝脏脂质代谢及自噬的影响

Effect of Paeonol on Liver Lipid Metabolism and Autophagy in Rats with Hyperlipidemia

目的探讨丹皮酚(Paeonol,Pae)对高脂血症大鼠肝脏脂质代谢及自噬的影响,为揭示Pae抗动脉粥样硬化(atherosclerosis,AS)早期病变的作用机制提供依据。方法采用维生素D2及高脂饲料联合应用法复制大鼠高脂血症模型,将大鼠分成Pae高剂量(300mg/kg)、中剂量(150mg/kg)、低剂量(75mg/kg)组,雷帕霉素组(0.2mg/kg),阿托伐他汀组(5mg/kg),分别每天灌胃一次,连续6周,模型组和正常组给予等容量溶媒灌胃。采用全自动生化分析仪检测血脂和肝脂水平,光镜下对肝脏脂肪变性程度进行评分,电镜下观察自噬小体,免疫组织化学法观察肝脏中自噬相关因子微管相关蛋白1轻链3-Ⅱ型(microtubule-associated protein 1light 3,type 2,LC3Ⅱ)、p62及过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)的表达。结果 Pae可以降低血清和肝脏中甘油三酯、总胆固醇水平及肝系数,减轻肝脏脂肪变性程度,减少脂滴数量,促进自噬小体的产生,上调肝细胞中LC3Ⅱ、PPARγ表达,下调p62表达。结论 Pae可以促进脂质代谢并升高肝脏自噬小体形成及相关因子表达。

Objective To investigate the effect of Paeonol （Pae） on liver lipid metabolism and autophagy in rats with hyperlipidemia, and to provide a basis for the mechanism of action of Pae in the treatment of early lesions of atherosclerosis （AS）. Methods A rat model of hyperlipidemia was established by high-fat diet with vitamin D2, and the rats were divided into high-, middle-, and low-dose Pae groups （with doses of 300, 150, and 75 mg/kg, respectively）, Rapamycin group （0.2 mg/kg）, and atorvastatin group （5 mg/kg）. The drugs were given by gavage once a day for 6 consecutive weeks. The model group and the normal group were given an equal volume of solvent by gavage. An automatic biochemical analyzer was used to measure the levels of blood lipids and liver lipids; hepatic steatosis was scored under a light microscope; autophagosomes were observed under an electron microscope; immunohistochemistry was used to measure the expression of microtubule-associated protein 1 light 3, type Ⅱ （LC3Ⅱ）, p62, and peroxisome proliferator-activated receptor gamma （PPARγ） in the liver. Results Pae reduced the levels of triglyceride and total cholesterol in serum and the liver and liver index, alleviated the degree of hepatic steatosis, reduced the number of lipid drops, and promoted the production of autophagosomes. It also increased the expression of LC3Ⅱ and PPARγ and reduced the expression of p62 in hepatocytes. Conclusion Pae can promote lipid metabolism, increase the formation of liver autophagosomes, and upregulate the expression of related factors.