GPER通过激活AMPK-PDHA1/CPT1B通路改善脓毒症肝细胞线粒体功能障碍的机制研究*

doi:10.3870/j.issn.1672-0741.25.08.013

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (1): 61-67.doi: 10.3870/j.issn.1672-0741.25.08.013

GPER通过激活AMPK-PDHA1/CPT1B通路改善脓毒症肝细胞线粒体功能障碍的机制研究^*

杨镭镭, 彭坚, 冯小静, 高珊, 陈真^△

武汉市第三医院, 武汉大学同仁医院麻醉科, 武汉 430060

收稿日期:2025-08-04 出版日期:2026-02-15 发布日期:2026-02-10
通讯作者: ^△E-mail:18062519550@189.cn
作者简介:杨镭镭,女,1981年生,副主任医师,医学硕士,E-mail:329428382@qq.com
基金资助:
^*湖北省自然科学基金资助项目(No.2023AFC030)

GPER Ameliorates Mitochondrial Dysfunction in Sepsis-induced Hepatocytes via Activating the AMPK-PDHA1/CPT1B Pathway

Yang Leilei, Peng Jian, Feng Xiaojing et al

Department of Anesthesiology, Wuhan No.3 Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China

Received:2025-08-04 Online:2026-02-15 Published:2026-02-10
Contact: ^△E-mail:18062519550@189.cn

摘要/Abstract

摘要： 目的探讨G蛋白偶联雌激素受体(GPER)改善脓毒症患者肝细胞线粒体功能障碍的可能作用机制。方法采用AML-12肝细胞构建内毒素(LPS)诱导的脓毒症模型,设空白对照组、LPS组、LPS+G1组(GPER激动剂)和LPS+G15组(GPER拮抗剂)。通过CCK-8、流式细胞术、ELISA等技术评估细胞活力、凋亡、炎症因子(TNF-α,IL-1β,IL-6)及能量代谢指标(ATP/AMP)。采用qRT-PCR和Western blot分别检测GPER的mRNA和蛋白表达水平。采用Western blot分析AMPK磷酸化(p-AMPK)及其下游代谢酶丙酮酸脱氢酶E1α亚基(PDHA1)和肉碱棕榈酰转移酶1B(CPT1B)的蛋白表达。通过激光共聚焦显微镜和流式细胞术分别检测线粒体活性氧(mtROS)和线粒体膜电位(ΔΨm),并利用透射电镜观察线粒体超微结构。结果在LPS诱导的肝细胞脓毒症模型中,GPER激动剂G1不仅能显著改善细胞活力、抑制凋亡并减轻炎症反应,还能有效逆转能量代谢障碍、降低氧化应激水平(均P<0.01),并修复线粒体超微结构损伤。相反,GPER拮抗剂G15不仅完全阻断了G1的保护作用,还进一步加剧了上述各项损伤指标(均P<0.01)。结论 GPER通过激活AMPK-PDHA1/CPT1B轴,优化糖脂代谢,恢复线粒体能量稳态并抑制氧化应激,从而减轻脓毒症肝细胞损伤,为脓毒症肝损伤的性别差异化治疗提供新靶点。

关键词: G蛋白偶联雌激素受体, AMP活化蛋白激酶, 丙酮酸脱氢酶E1α亚基, 肉碱棕榈酰转移酶1B, 脓毒症, 线粒体功能障碍

Abstract: Objective To investigate the possible mechanism by which G protein-coupled estrogen receptor(GPER)improves mitochondrial dysfunction in the hepatocytes of patients with sepsis. Methods An in vitro sepsis model was established by stimulating AML-12 hepatocytes with lipopolysaccharide(LPS).The cells were divided into four groups:control,LPS-treated,LPS + G1(a GPER agonist),and LPS + G15(a GPER antagonist)groups.Cell viability,apoptosis,the levels of inflammatory factors(TNF-α,IL-1β,and IL-6),and energy metabolism indicators(ATP/AMP)were assessed via techniques such as CCK-8,flow cytometry,and ELISA.The mRNA and protein expression levels of GPER were determined by RT-qPCR and Western blotting respectively.Western blot analysis was also employed to examine AMPK phosphorylation(p-AMPK)and the protein expression of pyruvate dehydrogenase E1 alpha subunit(PDHA1)and carnitine palmitoyltransferase 1B(CPT1B).Mitochondrial reactive oxygen species(mtROS)and mitochondrial membrane potential(ΔΨm)were measured via laser scanning confocal microscopy and flow cytometry,respectively.The ultrastructure of the mitochondria was observed via transmission electron microscopy. Results In the LPS-induced hepatocyte sepsis model,the GPER agonist G1 not only significantly improved cell viability,inhibited apoptosis,and reduced inflammatory responses but also effectively reversed energy metabolism disorders,decreased oxidative stress(all P<0.01),and repaired mitochondrial ultrastructural damage.In contrast,the GPER antagonist G15 not only completely abolished the protective effects of G1 but also further exacerbated these damage indicators(all P<0.01). Conclusion GPER protects against sepsis-induced hepatocyte injury via activating the AMPK-PDHA1/CPT1B axis,which enhances glucose and lipid metabolism,preserves mitochondrial energy homeostasis,and mitigates oxidative stress.These findings suggest that GPER is a potential novel target for sex-specific therapeutic strategies in sepsis.

Key words: G protein-coupled estrogen receptor, AMP-activated protein kinase, pyruvate dehydrogenase E1 alpha subunit, carnitine palmitoyltransferase 1B, sepsis, mitochondrial dysfunction

中图分类号:

R515.3

杨镭镭, 彭坚, 冯小静, 高珊, 陈真. GPER通过激活AMPK-PDHA1/CPT1B通路改善脓毒症肝细胞线粒体功能障碍的机制研究^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 61-67.

Yang Leilei, Peng Jian, Feng Xiaojing et al. GPER Ameliorates Mitochondrial Dysfunction in Sepsis-induced Hepatocytes via Activating the AMPK-PDHA1/CPT1B Pathway[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 61-67.

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GPER通过激活AMPK-PDHA1/CPT1B通路改善脓毒症肝细胞线粒体功能障碍的机制研究^*

GPER Ameliorates Mitochondrial Dysfunction in Sepsis-induced Hepatocytes via Activating the AMPK-PDHA1/CPT1B Pathway

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