首页|清肝活血方调控Caspase-4/Caspase-3/GSDME介导的细胞焦亡改善酒精性肝损伤

清肝活血方调控Caspase-4/Caspase-3/GSDME介导的细胞焦亡改善酒精性肝损伤

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
[目的]研究清肝活血方(QGHXR)通过调控半胱天冬酶(Caspase)-4/Caspase-3/GSDME细胞焦亡通路防治酒精性肝病(ALD)的作用机制.[方法]将 18 只C57BL/6 小鼠随机分为对照组、模型组和QGHXR组复制ALD小鼠模型.检测血清肝功能、血脂水平;苏木精-伊红(HE)染色及油红O染色观察肝脏病理改变及肝脏脂质沉积状况;实时荧光定量逆转录聚合酶链反应(qRT-PCR)、蛋白免疫印迹(Western Blot)法及免疫荧光染色检测Caspase-4/Caspase-3/GSDME通路相关基因及蛋白表达情况.[结果]与空白对照组比较,模型组小鼠肝组织三酰甘油(TG)水平明显升高(P<0.01),血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平升高(P<0.05),血清白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平升高(P<0.05);肝脏组织出现病理改变及脂质沉积现象;肝组织IL-1B、IL-6、TNF-α、NLRP3 mRNA表达水平升高.与模型组比较,QGHXR组小鼠肝组织TG水平明显降低(P<0.01),血清ALT、AST、总胆红素(TBIL)、总胆汁酸(TBA)水平降低(P<0.05),血清TG、IL-6、TNF-α水平降低(P<0.05)以及血清高密度脂蛋白(HDL)水平升高(P<0.01);血清中血脂、肝脏病理改变及脂质沉积现象缓解;GsdmeN、Caspase-4、Caspase-3 和C-Caspase-3 基因及蛋白水平降低(P<0.05).[结论]QGHXR可通过调节Caspase-4/Caspase-3/GSDME介导的细胞焦亡通路改善ALD小鼠肝损伤和脂质沉积.
Qinggan Huoxue Recipe regulates the cell pyroptosis mediated by Caspase-4/Caspase-3/GSDME to improve alcoholic liver injury
[Objective]To investigate the mechanism of Qinggan Huoxue Recipe(Qinggan Huoxue Recipe,QGHXR)in the prevention and treatment of alcoholic liver disease(ALD)by regulating Caspase-4/Caspase-3/GSDME pyroptosis pathway.[Methods]Eighteen C57BL/6 mice were randomly divided into control group,model group and QGHXR group to replicate the alcoholic liver disease model.Serum liver function and lipid levels were detected.Hematoxylin-eosin(HE)staining and oil red O staining were used to observe the pathological changes and lipid deposition in the liver.The expression of Caspase-4/Caspase-3/GSDME pathway related genes and proteins were detected by q-RT PCR,Western Blot and immunofluorescence staining.[Results]Compared with the control group,the liver TG level in model group was significantly increased(P<0.01),the serum ALT and AST levels were increased(P<0.05),and the serum IL-1β,IL-6 and TNF-α levels were increased(P<0.05).Liver tissue showed pathological changes and lipid deposition.The mRNA expression levels of IL-1β,IL-6,TNF-α and NLRP3 in liver tissue were increased.Compared with model group,the liver TG level in QGHXR group was significantly decreased(P<0.01),and the serum ALT,AST,TBIL and TBA levels were decreased(P<0.05).Serum TG,IL-6 and TNF-α levels were decreased(P<0.05)and serum HDL levels were increased(P<0.01).Serum lipid,liver pathological changes and lipid deposition were relieved.The levels of GsdmeN,Caspase-4,Caspase-3 and C-Caspase-3 genes and proteins were decreased(P<0.05).[Conclusion]QGHXR alleviates liver damage and lipid deposition in ALD mice by modulating the Caspase-4/Caspase-3/GSDME-mediated pyroptosis pathway.

Qinggan Huoxue Recipealcoholic liver diseasepyroptosisCaspase-4/Caspase-3/GSDME pathwaytraditional Chinese medicine compound

吴琰、圣炜、王立顺、张莉、计康、陈绘佳、陈珺明

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上海中医药大学研究生院,上海 200120

上海市闵行区中心医院,上海 201199

上海中医药大学附属龙华医院脾胃病研究所,上海 200032

清肝活血方 酒精性肝病 焦亡 Caspase-4/Caspase-3/GSDME通路 中药复方

上海市闵行区中医特色品牌专科项目上海市卫生健康委中医药科研项目

ZYPP-022022QN073

2024

10.11656/j.issn.1672-1519.2024.06.17

天津中医药
天津市中医药大学,天津中西医结合学会,天津中医药学会

天津中医药

CSTPCD
影响因子：0.998
ISSN：1672-1519
年,卷(期)：2024.41(6)