基于Cx43介导的Ca2+瞬变探讨ω-3多不饱和脂肪酸对术后肠麻痹的调控及机制研究

The prevention of postoperative ileus (POI) remains a tough task in major abdominal surgeries. The abnormal expression of gap junction connexin43 (Cx43) between intestinal Cajal cells (ICC) may be one of the main pathogenesis of POI. Previous studies suggest that omega-3 polyunsaturated fatty acids (omega-3 PUFAs) can up-regulate the expression of Cx43 effectively in POI mice, which promoted the recovery of intestinal movement. Nevertheless, the role of Cx43 playing in the mechanism of POI is yet to be explored. It is speculated that omega-3 PUFAs may affect Ca2 + transients by regulating the expression of Cx43 in ICC, thus the POI is prevented. In order to test this hypothesis, a Cx43-/- mice model of POI is used. With the help of laser scanning confocal microscope(LSCM) imaging, Western blot, and qRT-PCR, we could detect any possible relation between Cx43 and POI from the molecular level to the body level, On which the role of Cx43 mediated Ca2 + transient in the pathogenisis of POI might be discovered as well as the mechanism of omega-3 PUFAs in regulating it. The Cx43 mediated Ca2 + transient would possibly be the fundament of revealing the pathogenesis of POI. Since this new perspective is taken,the application of ω-3 PUFAs to POI might be feasible clinically in the future.

术后肠麻痹(POI)的防治是腹部外科学界的一个难点，Cajal细胞间的连接蛋白43（Cx43）表达异常可能是POI的重要发病机制之一。我们前期研究发现：ω-3多不饱和脂肪酸（ω-3 PUFAs）能有效上调POI小鼠Cx43的表达，促进肠运动功能的恢复，但其作用机制尚待探索。为此，我们提出假说：ω-3 PUFAs可能通过调控Cx43的表达，进而介导Cajal细胞内的Ca2+瞬变，从而减轻POI。为了验证这一假说，我们通过Cx43基因敲除小鼠POI模型，采用原位钙成像技术、Western blot、qPCR等手段，从分子、细胞、组织及动物整体水平等多方面探讨Cx43与POI的重要关系，明确Cx43介导的Ca2+瞬变在POI发病中的作用及ω-3 PUFAs的调控机制。本研究将从Cx43介导的Ca2+瞬变这个新视点为揭示POI的发生机制奠定基础，为ω-3 PUFAs应用于POI的防治提供新的思路。

术后肠麻痹(POI)的防治是腹部外科学界的一个难点，Cajal细胞间的连接蛋白43（Cx43）表达异常可能是POI的重要发病机制之一。我们通过Cx43基因敲除小鼠POI模型，采用原位钙成像技术、Western blot、qPCR等手段，从分子、细胞、组织及动物整体水平等多方面探讨Cx43与POI的重要关系，明确Cx43介导的Ca2+瞬变在POI发病中的作用及ω-3 PUFAs的调控机制。研究结果表明小鼠发生POI后，Cx43蛋白表达量降低，ICC内Ca2+瞬变强度降低；明确了小鼠ICC内Ca2+瞬变由Cx43介导，其强度和Cx43蛋白表达量呈正相关。Cx43表达量降低及其介导的Ca2+瞬变强度降低在小鼠POI发病中具有重要作用。ω-3 PUFAs对小鼠POI有治疗缓解作用，其机制是逆转了小鼠术后Cx43表达量降低及其介导的Ca2+瞬变强度减弱。本研究从Cx43介导的Ca2+瞬变这个新视点为揭示POI的发生机制奠定了基础，为ω-3 PUFAs应用于 POI 的防治提供新的思路。