基于“湿热胶着”从NLRP3激活调控“炎微环境”探讨Hp相关胃病发生及演变机制

Hp is the major cause of HPGD. Our studies have found that patients with spleen and stomach damp-heat syndrome have higher rate of Hp infection and more acute inflammation on gastric mucosal and higher expression of IL-1β.Besides, the quantity of Hp and lactobacillus on gastric mucosa and tongue coating changed, which lead to the imbalance of microenvironment. We speculate that change of "inflammatory microenvironment" lead by inflammation is a significant factor of the occurrence and evolution of HPGD. The Next-generation sequencing discovered that HPGD differentially expressed genes were closely related to the pathway of NLRP3. Based on previous studies, we proposed that the change of "inflammatory microenvironment" regulated by the activation of NLRP3 inflammasome is an critical factor for occurrence and evolution of HPGD. The damp-heat syndrome of spleen and stomach is the internal pathological factor of the occurrence and evolution of HPGD and abnormal expression of inflammation, which leads to HPGD from benign to malignant. From a holistic perspective to verify this hypothesis, the study will use modern technologies such as Quantitative Fluorescence PCR, Immunohistochemistry, Fluorescence In Situ Hybridization, high-throughput 16s amplicons sequencing, which provides theoretical and scientific basis for eradication of Hp and the prevention and treatment of gastric cancer by TCM.

Hp是引发Hp相关胃病（HPGD）主要因素，前期研究发现脾胃湿热证患者Hp感染率较高，胃黏膜炎症较为剧烈，体内IL-1β处于高表达状态，且胃黏膜及舌苔的Hp及乳酸杆菌数量发生改变，引起微生态的失衡，我们推测炎症后引起“炎微环境”的改变是HPGD发生及演变的重要因素；二代测序结果发现HPGD差异基因涉及NLRP3通路，在前期研究基础上我们提出： NLRP3炎症体家族激活调控“炎微环境”改变是HPGD发生及演变的重要关键，而脾胃湿热证是HPGD发生及演变炎症异常表达的内在病理因素引发HPGD由良性→恶性发展。本研究将运用荧光定量PCR、免疫组化、荧光原位杂交、高通量16s扩增测序等现代技术，从整体角度验证这一假说，为根除Hp中成药的研发，中医药防治胃癌提供理论基础及科学依据。

Hp感染是引发Hp相关胃病（HPGD）的主要因素。前期研究发现脾胃湿热证患者Hp感染率及胃黏膜的炎症均升高，体内IL-1β处于高表达状态，且胃黏膜、舌苔的Hp及乳酸杆菌数量发生改变，引起微生态的失衡；“外邪Hp”与“内生湿热”合并加重了胃黏膜的炎症反应，一定程度上提示着中医证型、炎症、菌群可能一定程度上决定Hp感染后的结局；通过高通量测序结果发现Hp相关差异基因涉及NLRP3通路。在前期研究基础，我们从NLRP3激活体胃内微生态改变着手，发现脾胃湿热组胃黏膜病理炎症程度呈现出重于脾气虚证组的趋势，脾胃湿热证组胃黏膜NLRP3、IL-1β mRNA、蛋白水平表达呈现出脾气虚证的趋势，且胃黏膜炎症剧烈脾胃湿热证组胃黏膜菌群的丰度明显低于脾气虚证组及正常对照组。随着对Hp相关胃病不同病种胃黏膜菌群进行测序发现，胃内菌群峰值呈现出正常对照组＞慢性浅表性胃炎组＞慢性萎缩性胃炎组＞胃癌组，进一步证实炎症及胃内菌群的改变参与Hp相关胃病胃黏膜良恶性演变的过程中，而脾胃湿热证及脾气虚证作为疾病发展的内在病理因素，贯穿至Hp相关胃病胃黏膜良性→恶性演变过程之中，本研究的研究结果为根除Hp证候倾向辨识，根除Hp中成药的研发，中医药防治胃癌提供理论基础及科学依据。