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目的:建立非酒精性脂肪肝(NAFL)大鼠模型,观察非酒精性脂肪肝大鼠肝组织细胞凋亡程度,探讨祛痰活血汤治疗NAFL的作用机制。方法:取SD雄性大鼠60只,在实验条件下饲养1周后,随机分为2组:正常对照组(10只),给予普通饲料;造模组(50只),给予高脂饮食。在给予高脂饮食后的第2周开始,将造模组50只大鼠又分为模型对照组、祛痰活血汤低、中、高剂量治疗组(ig,4.5,9,13 g.kg-1)、凯西莱治疗组(ig,0.03 g.kg-1)。模型对照组、正常对照组不用任何药物,代之以同等剂量的生理盐水。实验动物自由进水和进食,每2周称重1次,并相应调整用药剂量。按照以上分组给药方案,第8,9,10周末,从造模组随机各抽取1～2只大鼠处死,观察肝组织病理变化以及血液生化指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)等]。第10周处死所有大鼠,测定肝功能、血脂,取肝脏组织用10%甲醛溶液固定,石蜡包埋,连续切片,切片厚度为5μm,进行HE染色和TUNEL法检测细胞凋亡。结果:与正常对照组比较,模型对照组大鼠血清肝功能和血脂指标,肝组织病理炎症活动度、肝细胞凋亡表达指数均有明显的升高、加重(P<0.01);祛痰活血汤低、中、高剂量组、凯西莱组与模型对照组比,各项指标均能降低或减轻(P<0.05)。结论:祛痰活血汤可显著减轻NAFL大鼠肝组织脂肪变性程度,调节脂质代谢紊乱,一定程度上改善肝功能,降低组织细胞凋亡指数,这可能是其防治非酒精性脂肪肝病(NAFLD)的作用机制之一。
Objective: To establish a rat model of non-alcoholic fatty liver disease (NAFL) and observe the degree of hepatic apoptosis in rats with non-alcoholic fatty liver and explore the mechanism of Qutan Huoxue Decoction in treating NAFL. Methods: Sixty male Sprague Dawley rats were randomly divided into two groups: normal control group (n = 10), normal control group (n = 50) and high fat diet group. At the beginning of the second week after giving high-fat diet, 50 rats in model group were further divided into model control group, low, medium and high dosage expectorant group (ig, 4.5, 9, 13 g.kg -1), Kesilai treatment group (ig, 0.03 g.kg-1). Model control group, normal control group without any drug, replaced by the same dose of normal saline. Animals were allowed to enter water and eat freely, weighed once every two weeks, and the dose was adjusted accordingly. At the end of the 8th, 9th and 10th weeks, 1-2 rats randomly selected from the model group were sacrificed to observe the pathological changes of liver tissue and the blood biochemical indicators (ALT, Aspergillus oryzae) Aminotransferase (AST), triglyceride (TG), total cholesterol (TC), etc.]. All the rats were sacrificed on the 10th week. The liver function and blood lipids were determined. The liver tissues were fixed in 10% formaldehyde solution and embedded in paraffin. The sections were sliced to a thickness of 5 μm. HE staining and TUNEL were used to detect the apoptosis. Results: Compared with the normal control group, the serum liver function, blood lipid index, hepatic pathological inflammatory activity and hepatocyte apoptosis index in model control group were significantly increased (P <0.01); expectorant and activating blood Compared with the model control group, the indexes in the low, medium and high dose Tangxia group were lower or relieved (P <0.05). Conclusion: Expectorant Huoxue Decoction can significantly reduce the degree of hepatic steatosis, regulate lipid metabolism disorders, improve liver function and reduce apoptotic index in NAFL rats, which may be due to its prevention and treatment of NAFLD ) One of the mechanisms of action.