基于VN-MP-ACh通路研究电针改善重症急性胰腺炎肠道功能障碍的迷走-肠神经作用机制
批准号:
82104591
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
文谦
依托单位:
学科分类:
中西医结合临床基础
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
文谦
中文摘要
尽早减轻肠道炎症、恢复肠道动力是改善重症急性胰腺炎(SAP)预后的关键。目前研究表明电针对肠道的调节主要通过神经途径实现,但同时将外源性自主神经和肠道内在神经丛结合考虑的研究甚少。我们团队前期研究发现电针足三里穴可增加SAP大鼠迷走神经(VN)放电,促进肠道蠕动;并可能激活胆碱能抗炎通路,减轻肠道及胰腺损伤。我们推断——电针足三里可能通过兴奋VN腹腔支激活肠肌间神经丛(MP),增加神经递质乙酰胆碱(ACh)的释放,ACh一方面与巨噬细胞上的α7nAChR结合减轻肠道炎症;另一方面激动肠道平滑肌上的M3受体促进肠道动力。本课题拟记录SAP大鼠VN-MP-ACh通路中的神经电活动,检测神经递质、炎症介质的表达及肠道动力的变化,比较胰腺病理损伤及死亡率等,探讨电针足三里对VN-MP-ACh通路的影响,揭示其改善SAP肠道功能障碍的迷走-肠神经机制,为SAP“从肠论治”提供新靶点和临床策略。
英文摘要
The key to improve the prognosis of severe acute pancreatitis(SAP) is alleviating intestinal inflammation and restoring intestinal motility as soon as early. Research has now shown that the regulating effect of electroacupuncture is mainly depending on neural pathway, but few studies have considered the combination of exogenous autonomic nerve and internal plexus of the gut. We have previously demonstrated that electroacupuncture ST-36 affect intestinal peristalsis via increasing vagus nerve(VN) discharge, and may activate the cholinergic anti-inflammatory pathway to alleviate intestinal and pancreatic damage. Thus, we hypothesize that electroacupuncture ST-36 activate myenteric plexus(MP) by stimulating VN, and then acetylcholine(ACh)-based neurotransmitters are released, which not only bind to α7nAChR of macrophages to ease the inflammation, but also bind to M3 receptor of intestinal smooth muscles to recover intestinal motility. Our subject intends to record the neural electrical activity in the VN-MP-ACh pathway in SAP rats, detect the expression of neurotransmitters, inflammatory factors and changes in intestinal dynamics, compare the histological score of the pancreas and mortality of SAP to explore the effect of electroacupuncture ST-36 on the VN-MP-ACh pathway, reveal the vagal-enteric nervous mechanism improving prognosis of SAP and provide a new target and clinical strategy for the "treatment from the intestine" of SAP.
肠道是重症急性胰腺炎(SAP)病理生理过程中最早也是最易受损的器官之一。尽早减轻肠道炎症反应、恢复肠道动力及黏膜屏障功能,是改善SAP预后的关键,但目前药物治疗策略有限、疗效欠佳。针灸作为具有中医特色的非药物疗法,在临床实践中被证实能有效缓解SAP肠道功能障碍的多种不适症状,降低病死率。本课题为研究其作用机制成功建立了SAP肠道功能障碍的大鼠模型,通过对胰腺及肠道的病理评分,血清淀粉酶、脂肪酶、TNF-α、IL-6、内毒素、MPO等炎性介质及抗菌肽LL-37、Occludin、ZO-1等肠道黏膜屏障相关蛋白表达的测定,结果发现电针足三里穴修复了SAP大鼠胰腺及肠道病理、黏膜屏障损伤,减轻了胰腺、肠道及全身炎症反应,进而降低了SAP的严重程度、提高了存活率;通过对肠道推进率、肠肌间神经丛的神经元密度、胆碱能神经元比例的检测,结果表明电针足三里穴可以通过调节肠神经系统中的胆碱能神经元比例改善SAP 大鼠肠动力;本次研究还发现电针足三里穴通过调节肠道菌群的组成及增加短链脂肪酸的浓度,修复了SAP肠道屏障损伤,减少细菌内毒素入血,进而减轻胰腺及全身炎症反应;运用多导电生理记录系统分析各组大鼠迷走神经腹腔支放电及空肠肠压的变化,结果显示电针足三里穴使SAP大鼠迷走神经腹腔支放电幅度加大,并使空肠内压增加。本次研究结果表明电针足三里穴可能通过兴奋迷走神经腹腔支激活肠肌间神经丛,增加胆碱能神经元比例,在减轻肠道炎症的同时促进了肠道动力、修复了肠道黏膜屏障,进而改善SAP预后。证实了电针足三里穴作为SAP补充替代治疗方案的科学性,有助于临床进一步推广应用,使更多患者受益。
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