摘要
探讨蝙蝠蛾被毛孢菌丝体(Mycelium of Hirsutella hepiali Chen et Shen,MHCS)对代谢综合征的影响及作用机制。首先采用游离脂肪酸与MHCS处理肝细胞,检测自噬相关的LC3、p62水平与脂滴堆积。其次高脂喂养小鼠建立代谢综合征模型,将50周龄小鼠随机分为:对照组、模型组、给药组。干预至80周龄后每组随机抽取15只小鼠,测量口服葡萄糖耐量、空腹血糖、胰岛素、胰岛素样生长因子(IGF-1)水平,计算胰岛素抵抗指数(IRI);检测肝脏组织中LC3、p62与炎症相关p-NF-κB p65、NF-κB p65、IL-6与CXCL-8水平;观察肝脏内空泡面积、脂滴堆积与纤维化病理改变;其余小鼠继续饲养至110周龄,统计死亡率。结果表明,MHCS显著上调游离脂肪酸处理的肝细胞自噬水平,给药组小鼠口服葡萄糖耐量、胰岛素抵抗显著改善,自噬水平显著增加,炎症显著缓解,肝脏病理改善且生存率显著增高。提示MHCS可能通过激活肝脏自噬,改善小鼠代谢综合征。
To investigate the protective effects and possible mechanism of Mycelium of Hirsutella hepiali Chen et Shen （MHCS） on metabolic syndromes, free fatty acid and MHCS-treated hepatocytes were used for detecting autophagy-related LC3, p62 and lipid accumulation. Moreover, high fat diet fed mice were used to establish metabolic syndromes model. 50-weeks age mice were randomly divided into： control group, model group and MHCS group. At 80-weeks age, 15 mice were randomly chosen from each group separately for examining oral glucose tolerance, serum insulin, insulin-like growth factor 1 （IGF-1）, hepatic LC3, p62, p-NF- rB p65, NF-KB p65, IL-6 and CXCL-8. Moreover, insulin resistance index （IRI） was calculated. Hepatic pathological changes, including vacuoles, lipids accumulation and fibrosis were observed. Remaining mice were fed with diet separately to 110 weeks-age for statistics of mortality. MHCS promoted autophagy of free fatty acid treated hepatocytes. Mice fed with high fat plus MHCS diet exhibited improved oral glucose tolerance, insulin resistance, hepatic pathology, inflammation, mortality and activated autophagy. The protective effects of MHCS against metabolic syndroms might be through the activation of hepatic autophagy.
出处
《药学学报》
CAS
CSCD
北大核心
2014年第5期615-621,共7页
Acta Pharmaceutica Sinica
基金
国家自然科学基金面上项目(81273529)
国家自然科学基金青年科学基金项目(81302805)
教育部长江学者和创新团队发展计划(IRT1007)
关键词
蝙蝠蛾被毛孢菌丝体
代谢综合征
自噬
胰岛素抵抗
脂肪肝
Mycelium of Hirsutella hepiali Chen et Shen
metabolic syndrome
autophagy
insulinresistance
fatty liver
