O'Keefe S J
Gastrointestinal Clinic, Groote Schuur Hospital, Cape Town, South Africa.
Dig Dis Sci. 1995 Nov;40(11):2465-8. doi: 10.1007/BF02063256.
Conventional measurement of mucosal turnover is based on labeling cellular DNA with [3H]thymidine, but because of the risk of genetic damage, this technique is not suitable for studies in normal human subjects. Consequently, we have measured mucosal protein turnover by a primed/continuous intravenous infusion of tracer quantities of [1-14C]leucine and measured its incorporation into mucosal protein at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by standard endoscopic techniques from the distal duodenum and gastric antrum. In addition, duodenal villous height and width were measured by microscopic micrometric techniques in order to calculate villous growth rate. Results demonstrated a mucosal protein turnover of 57 +/- 5% day in gastric antrum and 39 +/- 2% day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6 days, respectively. Average duodenal villous height was 433 +/- 77 micron, suggesting a villous growth rate of approximately 160 microns/day. As our mucosal protein turnover rates are similar to epithelial turnover rates measured by cellular labeling techniques, our results support the "intestinal proliferation" theory that suggests all mucosal elements follow similar turnover characteristics. In conclusion, the technique should provide a practical alternative method of studying the effect of disease upon mucosal regeneration and repair.
传统的黏膜更新测量方法是基于用[3H]胸腺嘧啶标记细胞DNA,但由于存在基因损伤风险,该技术不适用于正常人类受试者的研究。因此,我们通过向9名健康成年志愿者静脉内一次性/持续输注微量示踪剂[1-14C]亮氨酸来测量黏膜蛋白更新,并在4小时后测量其掺入黏膜蛋白的情况。通过标准内镜技术从十二指肠远端和胃窦获取黏膜样本。此外,用显微镜测微技术测量十二指肠绒毛高度和宽度,以计算绒毛生长速率。结果显示,胃窦黏膜蛋白更新率为57±5%/天,十二指肠为39±2%/天,提示黏膜更新率分别为1.8天和2.6天。十二指肠绒毛平均高度为433±77微米,提示绒毛生长速率约为160微米/天。由于我们的黏膜蛋白更新率与通过细胞标记技术测得的上皮更新率相似,我们的结果支持“肠道增殖”理论,即所有黏膜成分都具有相似的更新特征。总之,该技术应为研究疾病对黏膜再生和修复的影响提供一种实用的替代方法。