绞股蓝皂苷抑制Bcl2L12凋亡通路改善Apo E^(-/-)动脉粥样硬化小鼠肝脏脂质沉积  

Gypenosides Improve Liver Lipid Deposition in Apo E^(-/-)AS Mice by Inhibiting the Bcl2L12 Apoptosis Pathway

作　　者：赵卓 高浩 杨莹 王莹[2] 王群[2] 裴宇鹏[3] 宋囡[4] 韩晓伟[5] ZHAO Zhuo;GAO Hao;YANG Ying;WANG Ying;WANG Qun;PEI Yu-peng;SONG Nan;HAN Xiao-wei(Graduate School,Liaoning University of Traditional Chinese Medicine,Shenyang,110847;Engineering Technology Center of Traditional Chinese Medicine Innovation,Liaoning University of Traditional Chinese Medicine,Shenyang,110847;Liaoning Academy of Chinese Medical Sciences,Liaoning University of Traditional Chinese Medicine,Shenyang,110847;College of Medical Laboratory,Liaoning University of Traditional Chinese Medicine,Shenyang,110847;Department of Immunology and Pathogenic Biology,Liaoning University of Traditional Chinese Medicine,Shenyang,110847)

机构地区：[1]辽宁中医药大学研究生学院,沈阳110847 [2]辽宁中医药大学中药创新工程技术中心,沈阳110847 [3]辽宁中医药大学辽宁省中医药科学院,沈阳110847 [4]辽宁中医药大学医学检验学院,沈阳110847 [5]辽宁中医药大学免疫学与病原生物学教研室,沈阳110847

出　　处：《中国中西医结合杂志》2023年第10期1221-1227,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：辽宁省自然科学基金资助项目(No.2019-ZD-0966);辽宁省“百千万人才工程”资助项目(No.2021921104)。

摘　　要：目的探讨绞股蓝皂苷(GPs)通过Bcl2L12介导的凋亡通路防治动脉粥样硬化(AS)的作用机制。方法将Apo E^(-/-)小鼠随机分为模型组和GPs组(高脂喂养12周),C57BL/6J小鼠为正常组,每组各8只。GPs组灌胃GPs 2.973 g/kg4周。全自动生化分析仪检测血清血脂水平;HE染色及油红O染色观察肝脏病理改变及肝脏脂质沉积情况;q-RT PCR、Western Blot法及免疫组化染色检测Bcl2L12-Caspase-7/3通路相关基因及蛋白表达情况。结果与正常组比较,小鼠血清中TG、TC、LDL-C水平升高,HDL-C水平降低(P<0.01);肝脏组织出现病理改变及脂质沉积现象;凋亡蛋白酶活化因子(Apaf-1)、细胞色素C(Cyt C)、胱天蛋白酶(Caspase)-9、Caspase-7、Caspase-3 mRNA水平升高,Bcl2样蛋白12(Bcl2L12)m RNA水平降低(P<0.01);Apaf-1、Cyt C、Cleaved-Caspase-9、CleavedCaspase-7、Cleaved-Caspase-3蛋白水平升高,Bcl2L12蛋白水平降低(P<0.01);Caspase-3在肝脏组织表达升高,Bcl2L12在肝脏组织表达降低。与模型组比较,GPs组小鼠血清中血脂、肝脏病理改变及脂质沉积现象缓解,Bcl2L12基因及蛋白水平升高,CytC、Caspase-9、Caspase-7、Caspase-3基因及蛋白水平降低(P<0.01,P<0.05)。结论GPs可通过抑制Bcl2L12凋亡通路改善Apo E^(-/-)AS小鼠肝脏脂质沉积。Objective To explore the mechanism of gypenosides(GPs)preventing and treating atherosclerosis(AS)through Bcl2L12-mediated apoptosis pathway.Methods Apo E^(-/-)mice were selected as randomly divided into model group and GPs group(high-fat feeding for 12 weeks),and C57BL/6J mice were the normal group,with 8 mice in each group.In GPs group,GPs(2.973 g·kg^(-1))was given intragastrically for 4 weeks.Serum lipid levels were observed by automatic biochemical analyzer.Pathological changes and lipid deposition of liver tissue were observed by HE staining and oil red O staining.The expression of genes and proteins related to Bcl2L12-Caspase-7/3 pathway were detected by q-RT PCR,Western Blot and immunohistochemical staining.Results Compared with the normal group,the serum levels of TG,TC and LDL-C were increased,and the levels of HDL-C were reduced in model group(P<0.01),pathological changes and lipid deposition were in the liver,the levels of apoptotic protease activating factor(Apaf-1),cytochrome C(CytC),Caspase-9,Caspase-7 and Caspase-3 mRNA were significantly increased,while the mRNA level of Bcl2-like protein 12(Bcl2L12)were decreased(P<0.01),the protein levels of Apaf-1,Cyt C,Cleaved-Caspase-9,Cleaved-Caspase-7 and Cleaved-Caspase-3 were increased,while the level of Bcl2L12 protein were decreased(P<0.01).The expression of Caspase-3 in liver tissues was elevated and the expression of Bcl2L12 in liver tissues was reduced.Compared with the model group,the serum lipids,pathological liver changes and liver lipid deposition were relieved in GPs group,and the mRNA and the protein expression of Bcl2L12 increased while CytC,Caspase-9,Caspase-7,and Caspase-3 decreased(P<0.01,P<0.05).Conclusion GPs can inhibit lipid deposition in the liver of Apo E^(-/-)AS mice,and its mechanism may be related to Bcl2L12-mediated apoptosis.

关 键 词：绞股蓝皂苷 动脉粥样硬化 细胞凋亡 Bcl2样蛋白12 中药 

分 类 号：R285.5[医药卫生—中药学]