自噬对腹泻型肠易激综合征内脏高敏感性形成的作用机制

Mechanism of autophagy on the formation of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome

腹泻型肠易激综合征(IBS-D)是临床常见的功能性肠病,内脏高敏感性是IBS-D的核心病理生理机制之一,脊髓后角中枢敏化是形成IBS-D内脏高敏感性的重要途径。近年来研究发现,自噬可能通过调控中枢敏化的诱导、形成和维持,参与了内脏高敏感性的形成,其机制可能与自噬调节分子哺乳动物雷帕霉素靶蛋白(mTOR)影响中枢敏化NMDAR-PKC-ERK1/2关键信号通路相关。具体表现为激活mTOR抑制自噬,蛋白激酶C(PKC)活性升高,导致痛阈降低并提高机体对疼痛的敏感性;阻断mTOR促进自噬,PKC活性降低,可提升痛阈并降低机体对疼痛的敏感性。

Diarrhea-predominant irritable bowel syndrome(IBS-D) is a commonly clinical functional bowel disease. The visceral hypersensitivity is one of the core pathophysiological mechanisms of IBS-D. Spinal sensitization is an important way to form visceral hypersensitivity of IBS-D. In recent years, some studies have found that autophagy may participate in the formation of visceral hypersensitivity by regulating the induction, formation and maintenance of central sensitization, the mechanism may be related to the NMDAR-PKC-ERK1/2 pathway that regulated by the autophagy. It is that activation of mTOR could inhibit autophagy and increases the activity of PKC, which leads to the decrease of pain threshold and the improvement of pain sensitivity;On the other hand, blocking mTOR to promote autophagy could reduce the activity of PKC, which can increase the pain threshold and reduce the pain sensitivity.