基于交感神经活性调节探讨电针针刺合谷穴在重症急性胰腺炎中的抗炎作用及相关机制

Organ dysfunction brought by excessive inflammatory response is the leading cause of death in the early phase of severe acute pancreatitis (SAP). However, clinical effective therapy to control the inflammatory response is lacking. Autonomic nervous system is one of the key pathways in the neuroimmune crosstalk and recent studies suggested that it exerts anti-inflammatory effects in several diseases. Our previous study found that electroacupuncture at Hegu could reduce systemic cytokines in SAP rats then we hypothesize that the modulation of inflammation by electroacupuncture might be through sympathetic β-arrestin2/IkBα /NF-κB pathway. We will test our hypothesis in a rat model of SAP aiming to evaluate the effects of electroacupuncture on sympathetic tone, systemic inflammation and organ function. Specially, changes of β-arrestin2 /IkBα/NF-κB pathway after electroacupuncture will also be examined. In addition, chemical sympathectomy and β2-AR blockage are induced and small interfering RNAs are used to reduce levels of pancreas β-arrestin2 to assess the effects of electroacupuncture on inflammation and organ function. Our research will provide theoretical evidence for anti-inflammatory effects of electroacupuncture, and also, offer a new therapy in management of early SAP.

过度炎症反应引起的器官功能障碍是重症急性胰腺炎（SAP）患者急性期死亡主要原因，但目前并无确切有效治疗手段。免疫系统受自主神经调控，多种疾病中已证实调节自主神经活性发挥免疫调节作用。我们前期研究发现电针针刺合谷穴可减轻SAP大鼠炎症反应。由此推测，针刺抗炎效果可能与外周交感神经激活胰腺巨噬细胞β2-肾上腺素受体（β2-AR），调节β2-AR 信号调控蛋白β-arrestin2表达从而抑制NF-κB活化相关。本研究拟在SAP大鼠模型中行电针针刺合谷穴：①评估针刺对交感神经活性、炎症反应和器官功能的影响；②评估针刺对胰腺β-arrestin2表达，IkBα磷酸化和NF-κB活化作用；③阻断外周交感神经或β2-AR，针刺是否还能发挥抗炎作用；④siRNA技术沉默β-arresin2表达，针刺是否还能减轻炎症反应和器官功能损伤。本研究将为电针针刺抗炎提供理论依据，为SAP提供新的治疗方式。

过度炎症反应引起的器官功能障碍是重症急性胰腺炎患者急性期死亡主要原因，但目前并无确切有效治疗手段。免疫系统受自主神经调控，多种疾病中已证实调节自主神经活性发挥免疫调节作用。. 通过雨蛙素诱导轻型胰腺炎和胰管结扎诱导重症胰腺炎小鼠模型，我们发现：①电针针刺足三里穴位可以改善小鼠胰腺炎病情严重度，表现为血清淀粉酶和脂肪酶下降，以及胰腺损伤病理评分改善；②心率变异性评估小鼠自主神经活性，结果提示电针针刺足三里穴位平衡了自主神经功能，表现为交感的抑制和迷走的激活；③切断小鼠颈部迷走神经后，电针针刺足三里穴位的胰腺保护作用消失；④目前认为迷走神经通过激活胆碱能通路发挥抗炎作用。我们使用流式细胞技术分析胰腺炎症细胞比例，结果发现电针针刺足三里穴位对急性胰腺炎胰腺浸润的中性粒细胞和巨噬细胞比例并无影响。但电针针刺可明显提高巨噬细胞表面α7-胆碱能受体的表达。⑤在电针针刺之前给予α7-胆碱能受体抑制剂美卡拉明，电针针刺足三里穴位的胰腺保护作用消失。综上所述，电针针刺足三里穴位可减轻急性胰腺炎小鼠的病情严重度，这种保护作用通过激活迷走-胆碱能抗炎通路实现。本研究为电针在急性胰腺炎患者中的推广使用提供了理论依据。