Tanaka Fumio, Tominaga Kazunari, Fujikawa Yoshiko, Nagami Yasuaki, Kamata Noriko, Yamagami Hirokazu, Tanigawa Tetsuya, Shiba Masatsugu, Watanabe Toshio, Fujiwara Yasuhiro, Arakawa Tetsuo
Departments of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Dig Dis Sci. 2016 Dec;61(12):3478-3485. doi: 10.1007/s10620-016-4329-5. Epub 2016 Oct 7.
In patients with functional dyspepsia (FD), mild duodenal inflammation correlates with increased mucosal permeability. Enteric glial cells can produce glial cell line-derived neurotrophic factor (GDNF) to repair disrupted epithelial barrier function.
We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms.
Duodenal biopsies taken from FD patients and control subjects were used for analysis. GDNF protein expression and localization were examined. Cellular infiltration of eosinophils and mast cells was measured. We also examined the intercellular space between the adjacent epithelial cells at the apical junction complex using transmission electron microscopy.
In FD patients, expression of GDNF protein was significantly increased compared with controls, 107.3 (95.3-136.7) versus 49.3 (38.0-72.6) pg/mg protein (median (interquartile range), p = 0.006), respectively. GDNF was localized in enteric glial cells, eosinophils, and epithelial cells. The number of eosinophils was significantly greater in FD patients than in controls, 1039 (923-1181) versus 553 (479-598) cells/mm (p = 0.021), respectively. The intercellular space was dilated at the adherent junction in FD patients compared to control patients, 32.4 (29.8-34.8) versus 22.0 (19.9-26.1) nm (p = 0.002), respectively. Intercellular distance positively correlated with the frequency of postprandial fullness and early satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively). Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552).
Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.
在功能性消化不良（FD）患者中，轻度十二指肠炎症与黏膜通透性增加相关。肠胶质细胞可产生胶质细胞源性神经营养因子（GDNF）以修复受损的上皮屏障功能。
我们研究了十二指肠GDNF在FD病理生理学中的作用及其与消化不良症状的关联。
取自FD患者和对照受试者的十二指肠活检组织用于分析。检测GDNF蛋白表达及定位。测定嗜酸性粒细胞和肥大细胞的细胞浸润情况。我们还使用透射电子显微镜检查了顶端连接复合体处相邻上皮细胞之间的细胞间隙。
与对照组相比，FD患者中GDNF蛋白表达显著增加，分别为107.3（95.3 - 136.7）与49.3（38.0 - 72.6）pg/mg蛋白（中位数（四分位间距），p = 0.006）。GDNF定位于肠胶质细胞、嗜酸性粒细胞和上皮细胞中。FD患者中嗜酸性粒细胞数量显著多于对照组，分别为1039（923 - 1181）与553（479 - 598）个细胞/mm（p = 0.021）。与对照患者相比，FD患者紧密连接处的细胞间隙增宽，分别为32.4（29.8 - 34.8）与22.0（19.9 - 26.1）nm（p = 0.002）。细胞间隙距离与餐后饱胀感和早饱的频率呈正相关（分别为p = 0.001，r = 0.837和p =
