ANALYSIS OF GASTRIC MUCOSAL PROLIFERATION USING THE GROWTH FACTOR TRANSGENIC MICE

在胃溃疡等胃粘膜病变的恢复期，有多种生长因子参与其中。在本研究中，我们集中在肝细胞生长因子（HGF）和转化生长因子α（TGF α）。将金属硫蛋白基因启动子调控的HGF和TGF α转基因小鼠，在胃粘膜上皮广泛表达，通过北方杂交，发现HGF转基因在前胃、体胃和胃窦均有表达。用戊巴比妥麻醉小鼠并打开腹部。将金属探针用液氮冷却并附着在Serbium膜上。该方法被确立为实验性胃溃疡的冷却方法，但在本实验中实验性溃疡的大小不稳定。转基因和非转基因小鼠的溃疡大小没有差异，但在显微镜下观察，HGF小鼠的恢复期加快。HGF转基因小鼠溃疡周围血管内皮生长因子表达明显高于非转基因小鼠。这可能暗示了HGF和VEGF之间的血管生成协作参与了胃溃疡的恢复阶段。此外，TGF α小鼠通过鼻胃插管法摄入含有60%乙醇的150mM氯化氢。诱导小鼠急性胃粘膜病变，但TGF α小鼠和对照小鼠之间在溃疡形成方面没有差异。与非转基因小鼠相比，TGF α转基因小鼠的恢复倾向于加速。需要进一步的研究，包括时间过程，以澄清转基因小鼠和对照组中细胞增殖的差异。

Various growth factors are involved at recovery stage of gastric mucosal lesion such as gastric ulcer. In the present study, we focused on the hepatocyte growth factor (HGF) and transforming growth factor alpha (TGFa). Transgenic mice of HGF and TGFa whose promoter is under the control of metallothionein and the transgene is widely expressed in the epithelium including gastric mucosa.First, the expression of HGF transgene was universally expressed in forestomach, body and antrum by northern blot. Mice were anesthetized by Nembutal and opened the abdomen. Metal probe was cooled by liquid nitrogen and attached to the serosal membrane. This method is established as a cooling method for experimental gastric ulcer but the size of experimental ulcer was not stable in this experiment. The ulcers in transgenic and non-transgenic mice were not different in size but the recovery phase were accelerated in HGF mice under the microscopic examination. Vascular endothelial growth factor was more expressed around the ulcer formation in HGF mouse than in nontransgenic mice. This might implicate the involvement of angiogenic collaboration between HGF and VEGF in the recovery phase of gastric ulcer.Furthermore, TGFa mice ingested 150mM hydrogen chloride containing 60% ethanol by nasal to gastric intubation method. The mice were induced acute gastric mucosal lesions but there were no differences between TGFa mice and control mice in ulcer formation. The recovery tended to be accelerated in TGFa transgenic mice compared with non-transgenic mice. Additional study including time course is needed to clarify the difference of cell proliferation in transgenic mice and control.