水牛乳外泌体对高脂饮食诱导的小鼠肝脏脂质代谢紊乱的影响

Effect of Buffalo Milk Exosomes on Lipid Metabolism Disorder in Liver of Mouse Induced by High-fat-diet

为探究水牛乳外泌体对高脂饮食引起的小鼠肝脏脂质代谢紊乱的影响。该试验通过超高速离心的方法获得水牛乳外泌体,选取32只雄性C57BL/J6小鼠,随机分成正常对照组(ND组)、高脂日粮组(HFD组)、外泌体低剂量组(HFD-L组)和外泌体高剂量组(HFD-H组)。正常对照组小鼠和其他组小鼠分别用10%kcal对照饲料和60%kcal高脂饲料喂养8周。之后按分组情况每48 h分别灌胃磷酸盐缓冲液(PBS)或水牛乳外泌体(5和20 mg/kg),持续28 d。测定小鼠体重,脂肪和肝脏质量;检测血清和肝脏甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及血清谷草转氨酶(AST)和谷丙转氨酶(ALT)水平,并对肝脏组织进行HE染色和油红O染色。结果显示,通过超高速离心的方法可以获得完整的水牛乳外泌体;水牛乳外泌体可一定程度缓解高脂饮食诱导的小鼠体重增加;同时能以剂量依赖的方式显著降低高脂小鼠肝脏和血清TG、TC、LDL-C(P<0.05),提高高脂小鼠肝脏和血清HDL-C及降低血清AST、ALT(P<0.05),减缓高脂小鼠肝损伤。此外,HE染色和油红O染色结果均显示水牛乳外泌体可显著改善小鼠肝脏空泡变性,减少肝脏脂质沉积(P<0.05)。综上,水牛乳外泌体减轻了高脂肪饮食引起的肝脏脂质紊乱,为乳源性外泌体作为天然纳米药物的应用与开发提供理论依据。

To investigate the effects of buffalo milk exosomes on lipid metabolism disorders in the liver of mice induced by high-fat diet.In the experiment,exosomes were obtained through ultra-high speed centrifugation from buffalo milk,and a total 32 male C57BL/J6 mice were selected and randomly divided into normal control group(ND group),high-fat diet group(HFD group),low-dose exosomes group(HFD-L group),and high-dose exosomes group(HFD-H group).The mice in normal control group and the other groups were respectively fed with a 10%kcal control feed and a 60%kcal high-fat diet for 8 weeks.Subsequently,the mice were gavaged with either PBS or buffalo milk exosomes(5 and 20 mg/kg)every 48 h for a duration of 28 d,based on their respective groupings.The following indexes were detected:body weight,total adipose,liver tissue masses,levels of serum,liver triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),as well as serum gluten transaminase(AST)and alanine transaminase(ALT).Furthermore,liver tissue was subjected to HE staining and oil red O staining.The results showed that the intact buffalo milk exosomes could be obtained through ultra-high speed centrifugation,and buffalo milk exosomes could alleviate the weight gain caused by a high-fat diet in mice to a certain degree.Additionally,the exosomes significantly reduced liver and serum levels of TG,TC and LDL-C in a dose-dependent manner in high-fat mice,conversely increased liver and serum levels of HDL-C,and increased the serum levels of AST and ALT(P<0.05),slowing down the liver damage in high-fat mice.In addition,the results from both HE staining and oil red O staining demonstrated that buffalo milk exosomes could improve liver vacuolar degeneration and reduce liver lipid deposition in mice(P<0.05).In summary,the buffalo milk exosomes would possess the potential to alleviate liver lipid disorders induced by a high-fat diet,thereby provide a theoretical basis for the application and advancement of milk-derived exosomes as natural nanomedicines.