Nakshabendi I M, Downie S, Russell R I, Rennie M J
Department of Gastroenterology, Royal Infirmary, Glasgow.
Gut. 1996 Aug;39(2):176-9. doi: 10.1136/gut.39.2.176.
A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to investigate possible differences between the rate of duodenal mucosal protein synthesis in coeliac patients and normal control subjects.
Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received primed, continuous, intragastric (IG) and intravenous (i.v.) infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements.
Rates of duodenal protein synthesis were significantly greater in coeliac patients than in control subjects (i.v. tracer, coeliac v control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protein/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p < 0.05) suggesting smaller mucosal cell size in coeliac patients.
Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably increased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.
应用一种可靠、可重复的方法来测量胃肠道黏膜中的蛋白质合成，以研究乳糜泻患者与正常对照者十二指肠黏膜蛋白质合成速率之间可能存在的差异。
8例新诊断的未经治疗的乳糜泻患者（平均（标准差）年龄（51（10）岁，体重57（11）kg，身高160（6）cm）和7例对照者（年龄48（11）岁，体重71.5（12）kg，身高172（10）cm）在禁食过夜后接受L-[1-¹³C]亮氨酸和L-[1-¹³C]缬氨酸的初始、持续胃内（IG）和静脉内（i.v.）输注。在输注240分钟后进行内镜检查时获取十二指肠远端活检标本。在进行适当的质谱测量后，根据相对于细胞内游离氨基酸富集的蛋白质标记来计算蛋白质合成。
乳糜泻患者的十二指肠蛋白质合成速率显著高于对照者（静脉内示踪剂，乳糜泻患者与对照者相比，分别为3.58（0.45）%/小时对2.26（0.22）%/小时，p<0.05；胃内示踪剂，分别为6.25（0.97）%/小时对2.34（0.52）%/小时，p<0.01）。基于经胃内途径输注的示踪剂计算的黏膜蛋白质合成速率，乳糜泻患者高于对照者。乳糜泻患者的组织蛋白质/DNA比值显著降低（乳糜泻患者与对照者相比，分别为9.2（1.6）mg/μg对13.0（2.2）mg/μg，p<0.05），提示乳糜泻患者的黏膜细胞较小。
尽管在乳糜泻中观察到绒毛萎缩和细胞大小减小，但黏膜蛋白质合成速率却显著增加。这些结果表明，高蛋白合成速率可能是对乳糜泻患者高蛋白分解或黏膜细胞丢失速率的一种适应性反应。
