细胞焦亡与溃疡性结肠炎及中医药调控的研究进展

Advances in Research of Cell Pyroptosis, Ulcerative Colitis and Regulation with Traditional Chinese Medicine

细胞焦亡是不同于细胞坏死、凋亡、自噬的细胞程序性死亡的一种新形式,表现为细胞不断肿胀直至胞膜破裂,导致细胞内容物的释放进而激活强烈的炎症反应。细胞焦亡信号通路分为依赖于半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)的经典途径和依赖于半胱氨酸天冬氨酸蛋白酶-4,5,11(Caspase-4,5,11)的非经典途径,其中经典途径中Caspase-1的激活依赖于炎性小体发挥作用,非经典途径则是直接激活Caspase-4,5,11,最终导致gasdermin D(GSDMD)蛋白裂解,诱导膜孔隙的形成,白细胞介素-1β(IL-1β),IL-18成熟及释放,细胞膜破裂而发生焦亡。溃疡性结肠炎是一种消化系统常见的疑难病,具有病程长、易复发、难治愈等特点。目前其发病机制尚未完全清楚,但近年研究发现细胞焦亡对溃疡性结肠炎的发生发展有重要作用。中医药防治该病由来已久,临床疗效显著,研究发现中药防治该病的作用机制与炎症小体、焦亡产物IL-1β,IL-18等关系密切,中医药调控溃疡性结肠的分子机制与细胞焦亡存在一定相关性。故本文就细胞焦亡与溃疡性结肠炎之间关系及中医药的调控作用进行综述。

Pyroptosis,which is different from cell necrosis,apoptosis and autophagy,is a new type of programmed cell death. It is characterized by the swelling of cells until the cell membrane rupture,resulting in the release of cell contents and the activation of a strong inflammatory response. Pyroptosis signaling pathway is divided into the classical pathway dependent on Caspase-1 and the non-classical pathway dependent on Caspase-4,5 and 11. In classical pathway,activation Caspase-1 depends on inflammasome,whereas in non-classical pathway,Caspase-4,5,and 11 are activated directly. All of these result in the cleavage of gasdermin D(GSDMD)protein,the formation of membrane pores,the maturation and release of interleukin-1β(IL-1β)and IL-18,and the rupture of the cell membrane,and then leads to pyroptosis. Ulcerative colitis(UC)is a common disease of the digestive system. The UC course is long,easy to relapse,and difficult to cure. The pathogenesis of UC is not completely clear. In recent years,it has been found that pyroptosis plays an important role in the development of UC. Traditional Chinese medicine(TCM)has a long history of preventing and treating UC,with significant clinical effects. It is found that the mechanism of TCM in the prevention and treatment of UC is closely correlated with inflammasome,IL-1β and IL-18. The mechanism of TCM in preventing and treating UC is correlated with cell pyroptosis. Therefore,this paper reviews the relationship between cell pyroptosis and UC and the regulatory effect of TCM.