和厚朴酚对非酒精性脂肪肝模型大鼠的改善作用

Ameliorative effects of honokiol on non-alcoholic fatty liver disease of rat models

目的探讨和厚朴酚对高糖高脂乳剂诱导的非酒精性脂肪肝大鼠的影响。方法雄性SD大鼠灌服高糖高脂乳剂复制非酒精性脂肪肝模型,2周后按血清中总胆固醇(TC)水平随机分为模型对照组、辛伐他汀组及和厚朴酚高、低剂量组,正常对照组给予等量的生理盐水。分组后各组动物上午造模给药,下午治疗给药,正常对照组及模型对照组给予等量的0.5%羧甲基纤维素钠。药物干预6周后于末次给药前进行口服葡萄糖耐量试验(OGTT),末次给药后采集血清,测定血清中血脂及胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR),摘取肝脏、胰腺称质量并计算脏器系数,HE染色法观察肝脏病理形态学变化并进行非酒精性脂肪肝病活动度积分(NAS)评分。结果与正常对照组相比,模型对照组大鼠肝脏色泽黄腻、呈弥漫性肿大,脏器系数显著升高,呈典型脂肪肝病样变,NAS评分、血脂水平、FINS水平均显著升高,OGTT血糖曲线下面积(AUC)增大、HOMA-IR升高,NAFLD大鼠模型构建成功。与模型对照组相比,和厚朴酚各剂量组大鼠肝脏脂肪肝病样变减轻,血脂水平、AUC及HOMA-IR显著性降低。结论和厚朴酚能有效改善非酒精性脂肪肝模型大鼠的血脂代谢紊乱、肝细胞损伤及胰岛素抵抗。

Objective To investigate the effect of honokiol on nonalcoholic fatty liver disease in rats induced by high glucose and high fat emulsion. Methods Male SD rats were perfused with high glucose and high fat emulsion to generate the nonalcoholic fatty liver model. After 2 weeks, they were randomly divided into model control group, simvastatin positive group and honokiol high and low dose groups according to the level of serum total cholesterol(TC). At the same time, the normal control group was given the same amount of normal saline.The animals in each group were modeled in the morning and treated in the afternoon after grouping. The normal control group and the model group were given the same amount of 0.5% sodium carboxymethyl cellulose. After 6 weeks of drug intervention, oral glucose tolerance test(OGTT) was carried out before the last administration. After the last administration, serum was collected, serum lipid and insulin levels(FINS) were measured, insulin resistance index(HOMA-IR) was calculated, liver and pancreas were harvested and weighed, and organ coefficient was calculated. Hematoxylin & eosin(HE) staining was used to observe the pathomorphological changes of liver and the activity score(NAS) of nonalcoholic fatty liver disease was scored. Results Compared with the normal control group, the liver of the model control group was yellow and greasy, diffuse swelling, and the organ coefficient increased significantly, showing typical fatty liver disease features. The NAS score, blood lipid level and FINS level increased significantly.The area under OGTT blood glucose curve(AUC) and HOMAIR were increased. The NAFLD rat model was constructed successfully. Compared with the model control group, in each dose of honokiol groups, the features of fatty liver disease decreased, and the blood lipid level,AUC and HOMA-IR decreased significantly. Conclusion Honokiol can effectively improve the disorder of blood lipid metabolism, hepatocyte injury and insulin resistance in nonalcoholic fatty liver model rats.