余甘子总酚对动脉粥样硬化ApoE^(-/-)小鼠肝脏保护作用机制的研究  

Total phenols from Phyllanthus emblica L. alleviate fatty deposition and inflammation in liver of atherosclerotic ApoE^(-/-)mice

作　　者：邓欣 孟达 吴静宜 姜丙通 张雅琼 赵毅 车彦云 DENG Xin;MENG Da;WU Jing-yi;JIANG Bing-tong;ZHANG Ya-qiong;ZHAO Yi;CHE Yan-yun(Engineering Laboratory for National Healthcare Theories and Products of Yunnan Province,Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南省高校药食同源养生产品工程研究中心,云南中医药大学,云南昆明650500

出　　处：《中国病理生理杂志》2022年第9期1608-1617,共10页Chinese Journal of Pathophysiology

基　　金：云南省科技厅-云南中医药大学应用基础联合研究专项项目重点项目(No.2019FF002-012);云南省科技厅-云南中医药大学应用基础联合研究专项项目面上项目(No.202101AZ070001-212)。

摘　　要：目的:研究余甘子总酚对载脂蛋白E基因敲除(ApoE^(-/-))动脉粥样硬化模型小鼠的肝脏保护作用,初步探讨其作用机制。方法:建立高脂饮食诱导的ApoE^(-/-)小鼠动脉粥样硬化模型,给予余甘子总酚灌胃8周后,酶联免疫法检测小鼠血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平;观察小鼠肝脏病理模型切片;酶联免疫法检测小鼠肝脏组织匀浆中的总胆固醇(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)、白细胞介素6(IL-6)、IL-1β和肿瘤坏死因子α(TNF-α)的水平;Western blot法检测小鼠肝脏组织相关蛋白的表达。结果:余甘子总酚干预可降低ApoE^(-/-)小鼠血清中AST和ALT水平(P<0.05),减缓小鼠肝脏脂肪性病变及炎症细胞浸润现象;同时,余甘子总酚可显著降低肝脏组织匀浆中TC、TG和LDL-C水平,提高HDL-C水平(P<0.05),显著降低炎症因子IL-6、IL-1β和TNF-α含量(P<0.05);此外,余甘子总酚还可显著升高模型小鼠肝脏组织ATP结合盒转运体A1(ABCA1)蛋白水平(P<0.05),降低小鼠肝脏组织清道夫受体CD36和类固醇受体RNA激活物1(SRA1),以及Toll样受体4(TLR4)和核因子κB(NF-κB)P65蛋白表达水平(P<0.05)。结论:余甘子总酚可减少肝脏内胆固醇蓄积和炎症因子的释放,从而减轻动脉粥样硬化小鼠肝脏脂肪性病变和炎症反应。AIM:To study the liver protective effect and mechanism of total phenols from Phyllanthus emblica L.(PE)in ApoE^(-/-)atherosclerosis mice.METHODS:The atherosclerosis ApoE^(-/-)mice were induced by a high-fat diet for 8 weeks. The levels of aspartate transaminase(AST)and alanine aminotransferase(ALT)in serum of mice were detected by ELISA. Meanwhile,the pathological sections of liver of mice were observed. The levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in mouse liver tissue homogenate were measured by enzyme-linked immunoassay. The expression of related proteins in liver tissues of mice was detected by Western blot.RESULTS:Serum AST and ALT levels in ApoE^(-/-)mice were decreased by PE intervention(P<0. 05). Lipid deposition and inflammatory factors were alleviated. The contents of TC,TG and LDL-C in liver homogenate were significantly decreased(P<0. 05),while the content of HDL-C was increased(P<0. 05). Meanwhile,the levels of IL-6,IL-1β and TNF-α were obviously suppressed by PE(P<0. 05). In addition,the protein level of ATP binding cassette transporter A1(ABCA1)in liver tissue of mice was significantly increased(P<0. 05),while the levels of CD36 and steroid receptor RNA activator 1(SRA1)in liver tissues were reduced. Moreover,the protein expression of Toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)P65 were decreased(P<0. 05).CONCLUSION:Treatment with PE reduces the accumulation of cholesterol and the release of inflammatory factors in the liver,thus attenuating the fatty deposition and inflammation in the liver of atherosclerotic mice.

关 键 词：余甘子总酚 动脉粥样硬化 肝 脂质代谢 炎症 

分 类 号：R543.5[医药卫生—心血管疾病] R363.2[医药卫生—内科学]