TRPV1在应激性急性胃粘膜损伤形成中的作用及其机制

Acute gastric mucosal injury (AGML) is one of serious complications after serious burn and trauma, major surgeries and in acute and critically ill patients, but its pathogenesis is still completely to be remained.Transient receptor potential channels 1(TRPV1) plays an important role in sensory neurons of the nociceptive information transmission.It is reported that there is the high expression of TRPV1 in spinal afferent nerve and gastric mucosal . The results of our preliminary study shown there is a high expression of TRPV1 in DRG of rats induced by water immersion restraint stress , so we proposed that TRPV1 is maybe a key signaling molecule of the regeneration of AGML induced by WIRS in rats. From cells and animals, from spinal cord afferent neural pathway and gastric mucosa, this project is to be explore the roles and mechanism of TRPV1 in AGML induced by WIRS in rats by using the techniques of over-expression, RNAi, the methods of Western blot and ELISA and so on; and then it is disproved by using sufentanil pretreatment from the run of stress control, so as to obtain the solid evidences that TRPV1 participates and regulates in the regeneration of AGML induced by WIRS in rats. This project will clarify the regulative role and mechanism of TRPV1 in AGML regeneration so as to provide more sufficient scientific evidence for the establishment of TRPV1 as a new target for prevention and treatment of stress induced AGMLand stress traumatic related complications.

急性胃粘膜损伤（AGML）是临床上严重烧创伤、重大手术及急危重患者的常见并发症，然而其发病机制仍不完全清楚。瞬时受体电位通道1（TRPV1）在感觉神经元的伤害性信息传递过程中发挥重要作用，已有文献证实TRPV1在胃脊髓传入神经通路（DRG）以及胃粘膜都有表达,且我们前期研究发现TRPV1在浸水束缚大鼠（WIRS）的DRG上表达增高，因此推测TRPV1可能是应激后AGML形成的关键信号分子。本项目拟采用过表达、RNAi技术和western blot、ELISA等方法，分别从细胞、动物两个水平，从脊髓传入神经通路和胃粘膜二个层面探讨TRPV1参与和调控应激性AGML形成的作用及其机制，并从应激控制的角度采用舒芬太尼预处理进行验证。本项目为确立TRPV1作为应激性AGML防治的新靶点提供更充分的科学依据，也为围术期采取应激控制防治AGML及应激性伤害相关并发症奠定坚实的理论基础。

急性胃粘膜损伤（AGML）是临床上严重烧创伤、重大手术及急危重患者的常见并发症，已有文献证实TRPV1、ASIC3在胃脊髓传入神经通路以及胃粘膜都高表达,且前期研究表明TRPV1、ASIC3在应激性AGML的发生中起重要作用。本项目采用Q-PCR、western blot、免疫组化等方法，分别从脊髓传入神经通路和胃粘膜二个层面探讨TRPV1、ASIC3在AGML发生中的作用及可能机制，并从应激控制的角度采用舒芬太尼预处理进行反证，旨在获得TRPV1、ASIC3参与和调控应激性AGML形成的可靠证据。本项目从WIRS不同时间的角度探索下丘脑、DRG、胃粘膜TRPV1、ASIC3 mRNA的动态变化过程，并计数胃粘膜损伤溃疡指数（UI）、测定胃液pH，同时检测应激不同时间时血清SOD、MDA的活力水平，观察大鼠应激状态下机体氧化和抗氧化能力，结果表明应激性溃疡发生过程中SOD、MDA可作为一个早期敏感指标进行检测，并为选择合适的时间对应激性溃疡进行干预提供依据。本项目亦初步探索TRPV1、ASIC3在AGML发生中的调控作用及其机制，为确立TRPV1作为应激性AGML防治的新靶点提供更充分的科学依据，也为围术期应激控制防治AGML的发生奠定坚实的基础。