Wang Xiao, Sun Jiasen, Wang Peng, Zhang Yimin, Chang Jiuyang, Duan Zhijun
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Laboratory of Integrated Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Biomedicines. 2025 Mar 27;13(4):802. doi: 10.3390/biomedicines13040802.
Gut barrier integrity plays a crucial role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Electroacupuncture (EA) at ST-36 can ameliorate inflammatory responses via stimulating the α7 nicotinic acetylcholine receptor (α7nAChR), but whether EA is effective in preserving the intestinal barrier of MAFLD has not been exactly illustrated. This investigation explored potential protection mechanisms of EA at ST-36 targeting the dismantled gut barrier in MAFLD. C57BL/6 mice were randomly allocated into several subgroups: control (CON), high-fat diet (HFD), HFD with EA, HFD with EA and α7nAChR inhibitor α-BGT, and HFD with EA and intestinal HO-1 knockout (KO). Body weight, liver weight, visceral fat index, and histopathological examination of the liver and the intestine were determined. Serum biological indexes were evaluated through corresponding kits. Furthermore, the expressions of HO-1, α7nAChR, gut barrier-associated proteins, and the molecular mechanisms in intestinal tissues were assessed via Western blot, RT-qPCR, immunohistology, or immunofluorescence examination. EA treatment decreased body weight, liver weight, and visceral fat index gain and mitigated liver function injury and abnormal lipid indexes, exhibiting less severity of hepatic steatosis, fibrosis, and inflammation responses of MAFLD. Lower gut permeability, less intestinal epithelial disruption, and upregulation of tight junction proteins after EA suggested the protective effects in attenuating intestinal epithelial barrier dysfunction. These protective effects were abolished by α-BGT or intestinal HO-1 deletion. Mechanistically, EA markedly enriched α7nAChR and HO-1 expression and mitigated phosphorylated p38 MAPK/NF-κB activation, which was lost in α-BGT or HO-1 KO treatment. The protective effects of EA at ST-36 in the pathogenesis of MAFLD may be attributed to the preserved intestinal barrier, thereby alleviating systemic inflammatory responses and preventing subsequent liver hits, where the α7nAChR-mediated HO-1/p38 MAPK/NF-κB pathway was crucial to maintain homeostasis.
肠道屏障完整性在代谢功能障碍相关脂肪性肝病（MAFLD）的发病机制中起关键作用。针刺足三里穴可通过刺激α7烟碱型乙酰胆碱受体（α7nAChR）改善炎症反应，但电针是否能有效保护MAFLD的肠道屏障尚未明确。本研究探讨了针刺足三里穴对MAFLD中受损肠道屏障的潜在保护机制。将C57BL/6小鼠随机分为几个亚组：对照组（CON）、高脂饮食组（HFD）、电针高脂饮食组、电针高脂饮食加α7nAChR抑制剂α - BGT组以及电针高脂饮食加肠道HO - 1基因敲除（KO）组。测定体重、肝脏重量、内脏脂肪指数，并对肝脏和肠道进行组织病理学检查。通过相应试剂盒评估血清生物学指标。此外，通过蛋白质免疫印迹法、逆转录定量聚合酶链反应、免疫组织化学或免疫荧光检查评估肠道组织中HO - 1、α7nAChR、肠道屏障相关蛋白的表达及分子机制。电针治疗可降低体重、肝脏重量和内脏脂肪指数增加，减轻肝功能损伤和异常血脂指标，减轻MAFLD的肝脂肪变性、纤维化和炎症反应严重程度。电针后肠道通透性降低、肠上皮破坏减少以及紧密连接蛋白上调表明其对减轻肠上皮屏障功能障碍具有保护作用。这些保护作用被α - BGT或肠道HO - 1缺失所消除。机制上，电针显著富集α7nAChR和HO - 1表达，减轻磷酸化p38丝裂原活化蛋白激酶/核因子κB激活，而在α - BGT或HO - 1基因敲除治疗中这种作用消失。电针足三里穴对MAFLD发病机制的保护作用可能归因于维持了肠道屏障，从而减轻全身炎症反应并预防后续肝脏损伤，其中α7nAChR介导的HO - 1/p38丝裂原活化蛋白激酶/核因子κB途径对维持体内平衡至关重要。
