温胆汤对代谢相关脂肪性肝病小鼠脂质代谢的影响

Effects of Wendan Decoction on lipid metabolism in mice with metabolism-related fatty liver disease

关键词:  温胆汤  代谢相关脂肪性肝病  脂质代谢  脂质过氧化  吡咯列酮

Key words:  Wendan Decoction  metabolically associated fatty liver disease  lipid metabolism  lipid peroxidation  pioglitazone

摘要:

[目的] 探讨温胆汤对代谢相关脂肪性肝病（MAFLD）模型小鼠药物干预的作用及潜在的分子机制。[方法] 将44只C57BL/6J雄性无菌小鼠适应性饲养1周后随机分为6组，分别为空白组、模型组、温胆汤低剂量组（低剂量组）、温胆汤中剂量组（中剂量组）、温胆汤高剂量组（高剂量组）、吡咯列酮治疗组（吡咯列酮组）；实验小鼠给予高脂饲料进行MAFLD造模，每天分别灌胃给予低、中、高剂量组（1.3，2.6和5.2 g/kg），吡格列酮组每天给予2.6 mg/kg。各干预治疗组小鼠均灌胃给药处理6周，每日1次。实验第14周末处死小鼠，比较6组小鼠肝指数、肝组织病理变化及脂肪含量，血清转氨酶、肝脏脂肪水平以及肝组织的氧化损伤指标丙二醛（MDA），超氧化物歧化酶（SOD）水平和脂质代谢重要基因和蛋白，固醇调节元件结合蛋白-1c（SREBP-1c）、脂肪酸合成酶（FAS）、二酰基甘油酰基转移酶2（DGAT-2）、硬脂酰辅酶A去饱和酶1（SCD-1）、脂酰辅酶A氧化酶（ACO）的表达水平。[结果] 模型组与空白组比较，小鼠的整体状态差，肝脏组织大面积脂肪变性及脂质浸润，血清转氨酶、肝脏脂肪水平明显升高，证实了高脂饲料饮食喂养8周成功构建了小鼠MAFLD模型；各药物干预治疗组小鼠肝指数、肝脏病理变化和肝脏脂肪水平，血清转氨酶、脂质过氧化水平和脂质代谢重要基因和蛋白表达均较模型组显著降低，其中，高剂量组和吡咯列酮组下降最为明显，各组结果比较差异具有统计学意义（P<0.05）。[结论] 不同剂量温胆汤均能明显改善MAFLD小鼠肝脏脂质沉积、肝功能，降低肝指数，可能与调节脂质代谢，降低肝组织中脂质过氧化水平和脂质代谢重要基因的表达有关。

Abstract:

[Objective] To investigate the effect of Wendan Decoction on drug treatment in metabolically related fatty liver disease (MAFLD) mice and the potential molecular mechanism. [Methods] After 1 week of adaptive feeding,44 C57BL/6J male mice were randomly divided into control group,model group,Wendan Decoction low-dose group (low-dose group),Wendan Decoction medium-dose group (medium-dose group),Wendan Decoction high-dose group (high-dose group) and pioglitazone group. The mice were given high-fat diet for MAFLD modeling. The low,medium and high dose groups were treated at 1.3,2.6 and 5.2 g/kg every day,respectively,and pioglitazone group was treated at 2.6 mg/kg every day. All mice in treatment groups were given intragastric administration for 6 weeks,once a day. The mice were killed at the end of the 14th week. The liver index,pathological changes of liver tissue and fat content of the 6 groups of mice were compared. The levels of serum transaminase and liver fat,malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue and the expression levels of the important genes and proteins of lipid metabolism,including SREBP-1c,FAS,DGAT-2,SCD-1 and ACO were detected. [Results] Compared with blank group,the overall state of mice was poor,the liver tissue was large area steatosis and lipid infiltration,serum transaminase and liver fat levels were significantly increased in model group,which confirmed that the MAFLD model of mice were successfully constructed after 8 weeks of high fat diet. Compared with model group,the liver index,liver pathological changes,liver fat level,serum transaminase,lipid peroxidation level and the expression of important genes and proteins in lipid metabolism of mice in all treatment groups were significantly decreased,the most significant decrease were in high-dose and pioglitazone groups,the differentiation of each group results were statistically significant (P<0.05). [Conclusions] Different doses of Wendan Decoction can significantly improve the liver lipid deposition,liver function and lower the liver index of MAFLD mice,which may be related to the regulation of lipid metabolism,the reduction of lipid peroxidation level in liver tissue and the expression of important genes and proteins in lipid metabolism.