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Azoramide ameliorates fructose-induced nonalcoholic fatty liver disease in mice.
Tissue & Cell ( IF 2.7 ) Pub Date : 2019-07-02 , DOI: 10.1016/j.tice.2019.07.001
Ridvan Bagci 1 , Varol Sahinturk 1 , Erhan Sahin 1
Affiliation  

Nonalcoholic fatty liver disease (NAFLD) is a frequent health problem. The insulin resistance and endoplasmic reticulum (ER) stress have been suggested to play important roles in the development and progression of NAFLD. However these processes and correlations have not fully been understood yet. Azoramide, an antidiabetic drug, has the potential for reducing insulin resistance and ER stress in obese mice. To date, there is no study on the effects of azoramide in NAFLD. The aim of this study was to investigate the potential role of azoramide on insulin resistance and ER stress in NAFLD induced mice. Forty Swiss Albino mice were assigned into control, azoramide, fructose and fructose + azoramide groups. Azoramide group received a single dose of azoramide at 150 mg/kg/day by gavage between 71-77th days. Fructose group was treated with 30% fructose solution for 70 days to generate NAFLD. Fructose + azoramide group was treated with 30% fructose for 70 days and then with a single dose of 150 mg/kg/day azoramide for 7 days. At the end of experiment, blood of mice was taken via cardiac puncture, and the livers were excised and weighted. GRP78 and XBP-1 levels were examined with immunohistochemistry in liver tissues. Liver steatosis was evaluated with H&E, Oil-Red O and Sudan-Black staining. ALT, AST, triglyceride, total cholesterol, VLDL, LDL, HDL, fasting glucose and insulin levels were measured in serum. The body and liver weights, insulin resistance, ER-stress markers, lipid profile, AST, ALT and histopathological changes increased by fructose treatment. Azoramide treatment was generally reversed all these changes. These data offer the first evidence to show that azoramide may serve as a potential treatment agent in NAFLD through decreasing the ER-stress and insulin resistance.

中文翻译:

Azoramide改善了果糖诱导的小鼠非酒精性脂肪肝疾病。

非酒精性脂肪肝疾病(NAFLD)是常见的健康问题。胰岛素抵抗和内质网应激被认为在NAFLD的发生和发展中起重要作用。然而,这些过程和相关性尚未完全被理解。Azoramide是一种抗糖尿病药,具有降低肥胖小鼠胰岛素抵抗和内质网应激的潜力。迄今为止,还没有关于氮杂酰胺在NAFLD中作用的研究。这项研究的目的是研究氮杂酰胺对NAFLD诱导的小鼠胰岛素抵抗和内质网应激的潜在作用。将40只瑞士白化病小鼠分为对照组,氮酰胺,果糖和果糖+氮酰胺组。Azoramide组在第71-77天之间通过管饲法接受了150 mg / kg /天的单剂量Azoramide。用30%果糖溶液处理果糖组70天以产生NAFLD。将果糖+氮杂酰胺组用30%果糖处理70天,然后用150mg / kg /天的单剂量氮杂酰胺处理7天。实验结束时,通过心脏穿刺采集小鼠血液,并切除肝脏并称重。用免疫组织化学方法检测肝组织中的GRP78和XBP-1水平。使用H&E,Oil-Red O和Sudan-Black染色评估肝脂肪变性。测定血清中的ALT,AST,甘油三酸酯,总胆固醇,VLDL,LDL,HDL,空腹血糖和胰岛素水平。果糖治疗可增加人体和肝脏的重量,胰岛素抵抗,内质网应激指标,脂质分布,AST,ALT和组织病理学变化。一般将所有的这些变化逆转为氮唑酰胺治疗。
更新日期:2019-11-01
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