Szymaszkiewicz Agata, Talar Marcin, Włodarczyk Jakub, Świerczyński Mikołaj, Bartoszek Adrian, Krajewska Julia, Mokrowiecka Anna, Małecka-Wojciesko Ewa, Fichna Jakub, Zielińska Marta
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.
Department of Digestive Tract Diseases, Medical University of Lodz, 90-153 Lodz, Poland.
Int J Mol Sci. 2022 Mar 24;23(7):3565. doi: 10.3390/ijms23073565.
Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.
近20%的老年患者患有便秘，但胃肠道（GI）随年龄增长发生的变化仍未得到充分阐明。在本研究中，评估了内源性阿片系统（EOS）的改变作为老年人便秘潜在原因的情况。对6个月、12个月和18个月大的小鼠进行了体外和体内胃肠道功能评估并比较。此外，还测定了阿片受体（MOP、DOP、KOP）激动剂对小鼠胃肠道功能以及功能性便秘患者小鼠组织和结肠活检中EOS成分表达的影响。与较年轻的组相比，最年长小鼠的胃肠道蠕动明显受损。体外实验中，组织对MOP和DOP激动剂而非KOP激动剂的反应随年龄减弱；对于DOP，在体内实验中得到了证实。在小鼠上消化道，Oprm1、Oprd1、Oprk1的表达随年龄下降；在结肠中，Oprm1表达增加。与较年轻组相比，50岁以上患者结肠活检中这些基因的表达没有差异。总之，胃肠道蠕动随年龄增长出现的损害可能是由于MOP和DOP对阿片激动剂激活的反应降低或EOS表达改变所致。
