促红细胞生成素对蛋氨酸胆碱缺乏饮食致成年雄性大鼠脂肪肝的潜在作用

Mona A. Said, Hala Anwer, S. Mansour, H. Abdallah
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摘要

随着近年来肥胖的激增,非酒精性脂肪性肝病(NAFLD)的患病率在全球范围内不断上升。本研究的目的是探讨促红细胞生成素(EPO)治疗对NAFLD的影响以及转化生长因子β1 (tgf - β1)的作用。通过蛋氨酸胆碱缺乏(MCD)饮食诱导成年雄性白化Wistar大鼠NAFLD。测定各试验组血清谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、白蛋白、胆红素、甘油三酯(TG)、总胆固醇(TC)、体重、肝脏重量及肝重/体重比,以评价其对肝脏的影响。取肝标本测定TG、TC、丙二醛(MDA)、还原性谷胱甘肽(GSH)、肿瘤坏死因子α (TNF-α)的含量,进行肝组织损伤的组织病理学检测和tgf - β1的免疫组化评价。与对照组相比,MCD饮食显著提高了血清AST、ALT水平,显著提高了肝质量和肝质量/体重比,显著提高了肝组织MDA、TNF-α和TGF-β1免疫组化评分。然而,肝脏GSH水平明显降低。肝脏TG、TC显著升高,血清TG、TC显著降低,体重、血清白蛋白、胆红素变化不显著。这些结果得到了肝组织病理变化的支持,肝细胞脂肪变性和炎症细胞浸润。EPO治疗逆转了这些结果。EPO治疗对NAFLD的发展具有肝保护作用,并能显著保护肝脏功能和结构,这可以通过EPO治疗的抗氧化、抗炎和抗纤维化作用来解释。
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THE POTENTIAL ROLE OF ERYTHROPOIETIN ON FATTY LIVER INDUCED BY METHIONINE CHOLINE DEFICIENT DIET IN ADULT MALE RATS
With recent upsurge in obesity, the prevalence of nonalcoholic fatty liver disease (NAFLD) is growing globally. The objective of this study was to investigate the influence of erythropoietin (EPO) therapy on NAFLD and the role of transforming growth factor beta one (TGFβ1). NAFLD was induced in adult male albino Wistar rats by administration of methionine choline deficient (MCD) diet. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, bilirubin, triglycerides (TG), total cholesterol (TC), body weight, liver weight and liver weight /body weight ratio were measured in different experimental groups to assess the liver affection. Liver samples were taken for measurement of TG, TC, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor alpha (TNF-α) as well as histopathological detection of hepatic tissue injury and immuno-histochemical assessment of TGFβ1. As compared to the control group, MCD diet was found to produce a significant increase in serum level of AST, ALT, liver weight and liver weight/ body weight ratio, accompanied with a significant increase in liver tissue MDA, TNF-α and TGF-β1 immuno-histochemical scoring. However, there was a significant decrease in hepatic GSH level. It also resulted in significant elevation in hepatic TG and TC, significant decrease in serum TG and TC levels and non-significant change in body weight, serum albumin and bilirubin. These results were supported by histopathological changes in hepatic tissues in the form of steatosis of hepatocytes and inflammatory cells infiltration. These results were reversed by EPO treatment. EPO treatment showed a hepato-protective effects against the development of NAFLD with a significant preservation of liver functions and structure that could be explained by the anti-oxidant, anti-inflammatory and anti-fibrogenic effect of EPO treatment.
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