大鼠实验性腺胃粘膜癌变过程中Ha－ras基因第12位密码子点突变的研究

A study of the establishment of a rat-model of gastric mucosal precancerous lesion and its reverse therapy

大鼠实验性腺胃粘膜癌变过程中Ｈａ－ｒａｓ基因第１２位密码子点突变的研究李春启，刘为纹，吕有勇，张青云，邓国仁，房殿春（第三军医大学西南医院消化内科）６３００３８癌基因的激活和抗癌基因的失活是肿瘤发生、发展的分子基础。ｒａｓ基因家族是目前研究得较深入的...

Ranitidine 0.03% in the diet(R),N-methyl-N'-nitro-N-nitrosoguanidine 50μl/ml added to the drinking ad libitum(MNNG),or the combination of 2(R+MNNG)were administered to Wistar rats for 20 weeks. The rats subsequently were raisded without R or MNNG for additional 23 weeks. A group of rats without drug administration were under observation for 43 weeks and served as the control.It was found that the rate of intestinal metaplasia (IM)in the glandular stomach was 22.5% with R,86.5% with MNNG and 100% with R+MNNG while it was only 7.5% in the control. The rate of Imand the number of metaplastic glands were significantly different between the R+MNNG group and MNNG group and between the R+MNNG group and R group as well.The therapeutic effects of retinoic acid (RA ) and sodium butyrate(SB)on the induced precancerous lesion were assessed, It was found that the rate of IM, moderate and severe dysplasia and gastric cancer and the number of metaplastic glands in the pyloric and the fundic glandular mucosa were significantly lower in RA treated group (72.0%, 24.0%,0% and 130.2±93.9 and 51.5±39.1 respectively) and SB treated group (60.0%, 20.0%,0% and 70.3±29.6 respectively) than in the untreated groups.The mucosal flaps with a pedicle from the stomach wall were transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3rd, 6th.9th and 12th month after transplantation. IM was observed in all the gastric grafts to the intestines photomicroscopically.On the basis of the findings listed above, it is concluded that the administration of R+MNNG is the method of choice to induce IM of gaatric mucosa in Wistar rats; RA and SB are safe and efficacious therapeutic agents in the reverse therapy for the precancerous lesion of the gastric glandular mucosa in Wistar rats;and IM of gastric mucosa might be a pH-related change, A hypothesis for the mechanism of IM of gastric mucosa is proposed.