GOAT/Ghrelin系统在断奶仔猪胃酸分泌中的作用及分子机制

The main factor that contributes to the segregated early weaning (SEW) synodrome is the lack of gastric acid secretion. How to effectively stimulate the piglet's endogenous gastric acid secretion is the key to prevent SEW synodrome. Ghrelin is one of the main factors regulating the development of gastric function, we found that ghrelin increased gastric H+ -K+ -ATPase activity. But, the regulating pathways and mechanisms remain unclear. GOAT is an acyl group transferase-like enzyme that catalyzes Ghrelin octanoylation,and both GOAT and acyl Ghrelin are expressed in gastric oxyntic mucosa X/A-like cells, which suggest that GOAT may play an important role in relationship between Ghrelin and gastric acid secretion, and is important to clarify the effect and mechanism of Ghrelin on gastric acid secretion. The present project focuses on GOAT for targets, to inhibit the enzyme activity and Ghrelin expression by GOAT inhibitor and RNAi technology respectively. Both in vivo and in vitro approaches will be used in order to unreval the effects of GOAT/Ghrelin system on gastric acid secretion and other-related gene expression, to investigate the effects and molecular regulating mechanisms in gastric acid secretion, which will has important values for digestive system disease prevention.

胃酸分泌不足是导致"仔猪早期断奶综合症"的主要原因。如何有效地激发仔猪内源性的胃酸分泌能力是预防该病的关键。Ghrelin是调节胃功能发育的主要因子之一，我们前期体外研究表明Ghrelin可以增加胃H+-K+-ATPase活性，具体作用途径和机制尚不清楚。GOAT是新发现的特异性催化Ghrelin的酰基化转移酶，与酰基化Ghrelin共表达于胃底泌酸腺X/A样细胞，提示GOAT在Ghrelin与胃酸分泌关系中扮演着重要角色，对阐明Ghrelin调节胃酸分泌的作用及机制具有重要意义。本研究拟以GOAT为靶点，采用GOAT抑制剂和RNAi技术分别抑制GOAT活性和Ghrelin的表达，体内外试验相结合深入探讨GOAT/Ghrelin系统对仔猪胃酸分泌和相关基因表达的影响，从分子水平上揭示GOAT/Ghrelin系统调节胃酸分泌的作用及机制，对消化系统疾病的防治有着重要价值。

胃酸分泌不足是导致"仔猪早期断奶综合症"的主要原因。如何有效地激发仔猪内源性的胃酸分泌能力是预防该病的关键。Ghrelin是调节胃功能发育的主要因子之一，但其具体作用途径和机制尚不清楚。GOAT是新发现的特异性催化Ghrelin的酰基化转移酶，与酰基化Ghrelin共表达于胃底泌酸腺X/A样细胞，提示GOAT在Ghrelin与胃酸分泌关系中扮演着重要角色，对阐明Ghrelin调节胃酸分泌的作用及机制具有重要意义。本研究以GOAT为靶点，采用GOAT抑制剂和RNAi技术分别抑制GOAT活性和Ghrelin的表达，体内外试验相结合研究探讨GOAT/Ghrelin系统对仔猪胃酸分泌和相关基因表达的影响，从分子水平上揭示GOAT/Ghrelin系统调节胃酸分泌的作用及机制。研究结果表明，Ghrlein基因沉默（shGhrelin）下调了Ghrelin mRNA的表达(P < 0.05) 。ELISA检测结果显示，shGhrelin降低了总Ghrelin和酰基化Ghrelin的合成水平(P < 0.05) 和分泌水平 (P < 0.05) 。并且shGhrelin降低了胃 H+-K+-ATPase和胃蛋白酶的活性。与酰基化Ghrelin水平相一致，shGhrelin降低了GOAT基因表达。研究还发现断奶时胃GOAT基因表达和蛋白质水平显著下降，GOAT mRNA表达与胃H+-K+-ATPase活性成显著正相关，这表明断奶前后胃可能通过自身调节GOAT水平来适应饮食的变化，表明GOAT可能参与对胃功能发育的调节。体外和体内GOAT抑制剂显著降低了酰基化Ghrelin的水平和H+-K+-ATPase的活性，这些结果提示GOAT可能通过降低酰基化Ghrelin的水平参与对胃酸的调控。