mTOR在电针治疗功能性消化不良中的一种调节机制

In the present study,significant effect of electroacupuncture(EA) was demonstrated in functional dyspepsia rats,which influenced the expression of ghrelin both in peripheral and central,as well as the level of p70S6K1 phosphorylation in gastrointestinal mucosal.The expression of ghrelin has the reciprocal relationship with the status of gastric mTOR activity.P70S6K1 is the key phosphorylated proteins from mTORC1 downstream playing an important role in initiating the synthesis and transcription.We maintain that there exists a mechanism that the expression of Ghrelin is regulated by mTOR activity in EA therapy for functional dyspepsia.Our project on the basis of previous research,further in-depth foucs on the influence of mTOR regulating the expression of ghrelin,which trigger the changes of related biological effects,especially the related translation initiation factor,involving the interaction between the downstream target protein of mTOR with the effect factors of intracellular phosphorylation process of AMPK-TSC1/2-mTORC1,when EA therapy for functional dyspepsia.By this study, we attempt to study based on Electroacupuncture treatment of functional dyspepsia,to find a new mechanism that mTOR activity regulates the expression of ghrelin which would provide novel information and singnificant clue to the study of acupuncture therapy for functional dyspepsia,obtaining better economic and social profit.

前期研究发现，电针对功能性消化不良有显著疗效，且影响着外周和中枢ghrelin的表达，以及胃肠粘膜的p70S6K1磷酸化程度。由于mTOR活性变化与ghrelin的表达存在密切的关联性，P70S6K1又是mTORC1下游重要的磷酸化蛋白调节因子。我们认为，在针刺治疗功能性消化不良的过程中，存在着基于mTOR活性的变化而调节Ghrelin表达的机制。本项目在前期工作基础上，进一步深入研究在电针治疗功能性消化不良过程中，mTOR 对ghrelin表达的影响而引发相关的生物效应变化，尤其是相关效应部位- - 胞内磷酸化AMPK-TSC1/2-mTORC1效应分子，与mTOR下游蛋白调节因子相互作用的过程。藉此项研究，我们试图基于电针治疗功能性消化不良的治疗学基础，发现一种mTOR调节ghrelin表达的机制。为针刺治疗功能性消化不良提供全新的研究资料和重要线索，具有较好的经济和社会效益。

胃肠动力障碍是功能性消化不良（FD）发生的重要病理生理基础，Ghrelin是一种重要的胃肠激素，在控制食欲、调节胃肠运动等方面发挥重要作用。本项目以多因素刺激法复制出的FD大鼠为实验对象，采用电针干预，综合利用行为学检测、神经电生理、分子生物学等技术，从电针对FD的治疗效果与Ghrelin的关系入手，研究Ghrelin与mTOR在电针治疗FD大鼠中的作用机制。结果发现，电针对FD大鼠的治疗效果与Ghrelin的表达变化存在明确关联性；其次，电针通过调节mTOR信号通路影响Ghrelin的合成与分泌；并且电针可通过磷酸化AMPK-TSC2-Rheb相关效应分子，与mTOR下游蛋白调节因子相互作用进而治疗FD。该研究结果为该病的预防和治疗提供了提供了新的思路和实验依据，具有较高的临床应用价值，产业化前景较好。