首页|基于脂质代谢异常探讨黄蛭口服液对急性高脂血症小鼠肝细胞凋亡及铁死亡的调节作用

基于脂质代谢异常探讨黄蛭口服液对急性高脂血症小鼠肝细胞凋亡及铁死亡的调节作用

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目的 基于脂质代谢异常探讨黄蛭口服液对急性高脂血症小鼠肝细胞凋亡和铁死亡的影响。方法 选取40只SPF级的C57BL/6小鼠,随机分为正常对照组、模型组、黄蛭口服液低、高剂量组、非诺贝特组,每组8只。各给药组分别按相应剂量灌胃给与黄蛭口服液和非诺贝特,正常对照组和模型组给予等量蒸馏水,连续给药5 d。除正常对照组外,其余各组在给药第3天时,肌肉注射四丁酚醛(Triton WR-1339)构建高脂血症模型。给药结束后检测小鼠血清血脂水平和肝功能两项,采用HE染色法观察肝脏病理变化、油红O染色观察脂质累积情况,用组织铁试剂盒检测肝组织中的铁含量。通过Western Blot检测肝脏ATP结合盒转运蛋白A1(ABCA1)、三磷酸腺苷结合转运蛋白G超家族成员5抗体(ABCG5)、肝X受体α(LXRα)、去唾液酸糖蛋白受体1(ASGR1)、活化的聚腺苷二磷酸核糖聚合酶(cleaved-PARP)、活化的含半胱氨酸的天冬氨酸蛋白水解酶(cleaved-caspase 3)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、转铁蛋白受体1(TFR1)、溶质载体家族7成员11(SLC7A11)、谷氨酸半胱氨酸连接酶(GCLM)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)蛋白表达变化。结果 与模型组相比,黄蛭口服液组可减少肝组织脂质空泡,减轻脂肪变性程度;降低肝脏中二价铁含量及血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)含量,同时升高高密度脂蛋白胆固醇(HDL-C)含量;黄蛭口服液组小鼠肝组织 ABCA1、ABCG5、LXRα、Bcl-2、SLC7A11、GCLM、GPX4、FTH1 表达水平明显升高,ASGR1、cleaved-PARP、cleaved-caspase 3、Bax、TFR1 表达水平明显下降。结论 黄蛭口服液可减轻急性高脂血症小鼠脂质代谢异常,从而缓解肝细胞凋亡及铁死亡。
The regulatory effect of Huangzhi oral liquid on hepatocyte apoptosis and ferroptosis in acute hyperlipidemia mice based on abnormal lipid metabolism
Objective To investigate the effect of Huangzhi oral liquid on ferroptosis and apoptosis of hepatocytes in acute hyperlipidemia mice based on abnormal lipid metabolism.Methods Forty SPF grade C57BL/6 mice were randomly assigned to the normal control group,the model group,Huangzhi oral liquid low-dose and high-dose groups,and fenofibrate group,with 8 mice in each group.All administration groups were given Huangzhi oral liquid and fenofibrate by gavage at corresponding doses,while the normal control group and the model group were given the same dose of distilled water for a period of 5 days.on the third day of administration,in addition to the normal control group,other groups were injected intramuscularly with Triton WR-1339 to establish a hyperlipidemia model.After the administration,the serum lipid levels and liver function in mice were detected.The pathological changes of liver were observed by HE staining and lipid accumulation was observed by oil red O staining.The iron content in liver tissues was detected by tissue iron assay kit.The changes in protein expression of ABCA1,ABCG5,LXRα,ASGR1,cleaved-PARP,cleaved-caspase 3,Bcl2,Bax,TFR1,SLC7A11,GCLM,GPX4 and FTH1 in liver were detected by Western Blot.Results Compared with the model group,Huangzhi oral liquid could reduce the lipid vacuoles in liver tissues,alleviate the degree of lipid degeneration,reduce the content of TC,TG,LDL-C,AST and ALT in serum,increase the content of HDL-C,increase the protein expression levels of ABCA1,ABCG5,LXRα,Bcl-2,SLC7A11,GCLM,GPX4 and FTH1 in mice liver tissues,reduce the protein expression levels of ASGR1,cleaved-PARP,cleaved-caspase 3,Bax and TFR1.Conclusion Huangzhi oral liquid can alleviate the abnormal lipid metabolism in acute hyperlipidemia mice,thus alleviates hepatocyte apoptosis and ferroptosis.

Huangzhi oral liquidLipid metabolismFerroptosisApoptosisAcute hyperlipidemia

张哲、庞晓妍、牛梦园、戴卫波、曾聪彦

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广州中医药大学附属中山中医院(广东中山 528400)

黄蛭口服液 脂质代谢 铁死亡 凋亡 急性高脂血症

2024

中国药师
国家药品监督管理局高级研修学院,武汉医药(集团)股份有限公司

中国药师

CSTPCD
影响因子:0.944
ISSN:1008-049X
年,卷(期):2024.28(9)