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S-腺苷甲硫氨酸对高脂高胆固醇饮食诱导的豚鼠肝和主动脉病变及氧化应激的保护作用。

Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

机构信息

Department of Medical Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Aziz Sancar Experimental and Medical Research Institute, Istanbul University, İstanbul, Turkey.

出版信息

Gen Physiol Biophys. 2024 Sep;43(5):411-421. doi: 10.4149/gpb_2024021.

Abstract

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-β1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

摘要

S-腺苷甲硫氨酸(SAM)是主要的甲基供体,具有抗氧化潜力。在这项研究中,研究了 SAM 在高脂肪/高胆固醇(HFHC)饮食诱导的非酒精性脂肪肝(NAFLD)中的预防和消退作用。它们被注射 SAM(50mg/kg,ip)6 周,同时给予 HFHC 饮食,或在 HFHC 饮食后 4 周。检测了血清转氨酶活性、总胆固醇(TC)、甘油三酯(TG)、细胞色素 p450-2E1(CYP2E1)和羟脯氨酸(Hyp)水平、氧化应激和抗氧化参数、α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β1(TGF-β1)的蛋白表达以及肝脏的组织病理学变化。SAM 治疗减轻了 HFHC 饮食引起的血清转氨酶活性和肝 TC、TG、CYP2E1、Hyp、α-SMA 和 TGF-β1 表达的增加,并改善了促氧化剂-抗氧化剂平衡。SAM 治疗降低了肝脂肪变性、炎症和纤维化的组织病理学评分。SAM 治疗还降低了 HFHC 喂养动物的 TC、二烯共轭物水平和主动脉中膜内的脂质空泡的增加。在 HFHC-豚鼠的回归期也检测到了这些保护作用。总之,SAM 治疗可有效预防和消退 HFHC 诱导的肝和主动脉病变,并降低 NAFLD 豚鼠的氧化应激。

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