水蛭对非酒精性脂肪肝病小鼠的保护作用及其机制
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篇名: 水蛭对非酒精性脂肪肝病小鼠的保护作用及其机制
TITLE: Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease
摘要: 目的 探讨水蛭对非酒精性脂肪肝病(NAFLD)小鼠的保护作用及潜在机制。方法将雄性载脂蛋白E基因敲除(ApoE-/-)小鼠随机分为模型组和水蛭低、高剂量组(0.45、0.9g/kg),每组10只;另取同周龄野生型雄性C57BL/6J小鼠10只,作为对照组。对照组小鼠以基础维持饲料喂养,其余各组小鼠以高脂饲料喂养12周以建立NAFLD模型。第13周,各药物组小鼠灌胃相应药液,每天1次,连续8周。末次给药后,测定各组小鼠的体重、肝脏质量,并计算肝脏指数;检测其血清核因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平;观察其肝组织病理形态学变化,并检测肝组织中过氧化物酶体增殖物激活受体γ(PPARγ)、沉默信息调节因子1(SIRT1)蛋白的表达情况。结果与对照组比较,模型组小鼠肝组织可见较多的脂肪空泡和炎症细胞浸润,并有明显的脂质堆积;其体重、肝脏质量及肝脏指数和血清NF-κB、TNF-α、IL-1β、IL-6、TC、TG、LDL-C水平均显著升高,血清HDL-C水平和肝组织中PPARγ、SIRT1蛋白的表达水平均显著降低(P<0.01)。与模型组比较,水蛭低、高剂量组小鼠肝组织病理改变均有所缓解;其体重、肝脏质量及肝脏指数和血清NF-κB、TNF-α、IL-1β、IL-6、TC、TG、LDL-C水平均显著降低,血清HDL-C水平和肝组织中PPARγ、SIRT1蛋白的表达水平均显著升高(P<0.05或P<0.01)。结论水蛭可能通过激活PPARγ、SIRT1蛋白的表达来调节肝脏脂质代谢、抑制炎症反应,从而发挥对NAFLD的改善作用。
ABSTRACT: OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease (NAFLD) in mice. METHODS The male ApoE-/- mice were randomly divided into the model group and Hirudo low- dose and high-dose groups (0.45, 0.9 g/kg), with 10 mice in each group; another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically, once a day, for 8 consecutive weeks. In the 13th week, the body weight and liver weight of mice in each group were measured after the last medication, and the liver index was calculated; the serum levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected; the liver pathomorphological changes were observed; the protein expressions of peroxisome proliferator-activated receptor γ(PPARγ) and silence information regulator type 1 (SIRT1) were detected. RESULTS Compared with the control group, the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells, with significant lipid accumulation; the body weight, liver weight and liver index of the mice, and serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C significantly increased, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased (P<0.01). Compared with the model group, the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups; the body weight, liver weight and liver index, the serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C decreased significantly, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly (P<0.05 or P<0.01). CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1, thus having a significant ameliorative effect on NAFLD.
期刊: 2024年第35卷第10期
作者: 温紫云;韩倩倩;吕晴;魏亮;聂文强;洪敏;潘芸芸
AUTHORS: WEN Ziyun,HAN Qianqian,LYU Qing,WEI Liang,NIE Wenqiang,HONG Min,PAN Yunyun
关键字: 水蛭;非酒精性脂肪肝病;ApoE-/-小鼠;脂质堆积;炎症反应;SIRT1;PPARγ
KEYWORDS: Hirudo; non-alcoholic fatty liver disease; ApoE-/- mice; lipid accumulation; inflammatory response; SIRT1;
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