中医药调控PI3K/AKT信号通路干预溃疡性结肠炎研究进展

Research Progress of Intervention of TCM on PI3K/AKT Signaling Pathway in Ulcerative Colitis

通过干预磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路中的相关因子而发挥治疗作用的中医药疗法可分为清热解毒燥湿、活血化瘀止血、健脾温肾祛湿和攻补兼施等,能有效遏制UC的发生发展,其作用机制为:(1)通过抑制上游信号因子表皮生长因子受体,进而抑制PI3K/AKT通路,减少肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-6(interleukin-6,IL-6)在内的促炎细胞因子的表达,降低结肠炎症反应,减轻炎症所引起的结肠组织损伤;(2)直接作用于PI3K-AKT通路,进而抑制核转录因子-κB(nuclear transcription factor-κB,NF-κB)的表达,减少细胞凋亡和促炎因子的表达,缓解肠黏膜组织损伤,修复肠黏膜屏障功能的完整性;(3)通过PI3K/AKT途径下调辅助性T细胞17(T helper cell 17,Th17)和辅助性T细胞3(T helper cell 3,Th3)的分化,调节免疫反应及细胞凋亡,改善肠黏膜屏障,缓解UC结肠炎症反应。中医药具有成分复杂,有效成分作用靶点多,治疗途径多样等特点,但其具体分子生物学作用机制尚未完全明确,今后,需对分子生物学作用机制进行深入研究,为临床治疗溃疡性结肠炎等易反复发作的消化性疾病和新药的开发提供新策略。

TCM therapies that exert therapeutic effects by intervening related factors in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway can be divided into heat-clearing,detoxifying,and drying-dampness type,the tpye of activating blood circulation and removing blood stasis,the type of invigorating spleen and warming kidney to eliminate dampness,and the type of simultaneous elimination and reinforcement,etc.,which can effectively inhibit the occurrence and development of UC.The mechanism of action is as follows:(1) By inhibiting the upstream signaling factor EGFR,the PI3K/AKT pathway is inhibited,the expression of proinflammatory cytokines including TNF-α,IL-1β and IL-6 is reduced,the colon inflammatory response is lowered down,and the colon tissue injury caused by inflammation is reduced;(2) Directly acting on the PI3K-AKT pathway,the NF-κB expression is inhibited,the apoptosis and proinflammatory cytokine expression are reduced,the intestinal mucosal tissue injury is relieved,and the integrity of the intestinal mucosal barrier function is repaired;(3) The differentiation of Th17 and Th3 cells is down-regulated through the PI3K/AKT pathway,the immune response and apoptosis are regulated,the intestinal mucosal barrier is improved,and the inflammatory response of UC colon is relieved.TCM has the characteristics of complex components,multiple targets of effective components,and various treatment pathways,but its specific molecular biological mechanism has not been fully clarified.In the future,in-depth research on the molecular biological mechanism is needed to provide new strategies for the clinical treatment of recurrent digestive diseases such as ulcerative colitis and the development of new drugs.