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、0.9 g/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。
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 lowdose 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 receptorγ(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 PPARγand 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 PPARγand SIRT1 in liver tissue all increased significan
作者
温紫云
韩倩倩
吕晴
魏亮
聂文强
洪敏
潘芸芸
WEN Ziyun;HAN Qianqian;LYU Qing;WEI Liang;NIE Wenqiang;HONG Min;PAN Yunyun(Dept.of traditional Chinese medicine,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080,China;Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)
出处
《中国药房》
CAS
北大核心
2024年第10期1193-1197,共5页
China Pharmacy
基金
国家自然科学基金项目(No.82074139)
广东省中医药局科研项目(No.20213013,No.20211232)。
