Laboratory of Neurobiology, College of Animal Medicine, China Agricultural University, Beijing, 100193, China.
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Endocr J. 2021 Apr 28;68(4):485-502. doi: 10.1507/endocrj.EJ20-0332. Epub 2021 Jan 7.
Female, especially for pregnant female, are vulnerable to psychological stress. The morphology and metabolism of the maternal intestine are both obviously changed during pregnancy, thus making intestinal health status more fragile under psychological stress. The aim of the present study was to investigate the role of CRH and CRHR1 in the pregnant maternal intestine under psychological stress, thus exploring the mechanism of psychological stress in the pregnant maternal intestine. Bama miniature pigs were divided into the control and restraint stress groups from the first day of pregnancy. After restraint stress treatment for 18 consecutive days (D18), the plasma, duodenum, jejunum, ileum and colon were collected for study. Pregnant Bama miniature pigs subjected to restraint stress had significantly elevated CRH, adrenocorticotropic hormone (ACTH) and cortisol (COR) levels in plasma. Consistent with the increase in CRH levels, we observed enhanced oxidative stress levels in the intestine, which resulted in intestinal mucosal injury, including impaired intestinal morphology, a reduced number of goblet cells and proliferating cell nuclear antigen-positive cells, decreased expression of MUC2 and tight junctions, and elevated expression of CRHR1 and caspase-3. Moreover, exogenous CRH could directly promote IPEC-J2 cell apoptosis and influence its cell cycle (S and G2 phase) through CRHR1, and antalarmin could alleviate this phenomenon. Therefore, our results illustrated that the intestinal dysfunction of pregnant Bama miniature pigs was caused by restraint stress, and these changes were associated with the enhanced expression of CRH and CRHR1 in the intestine.
女性，尤其是孕妇，易受到心理应激的影响。孕妇的肠道形态和代谢均发生明显改变，因此在心理应激下肠道健康状况更为脆弱。本研究旨在探讨 CRH 和 CRHR1 在心理应激孕鼠肠道中的作用，从而探索心理应激对孕鼠肠道的影响机制。选取妊娠第 1 天的巴马小型猪分为对照组和束缚应激组，连续束缚应激 18 天（D18）后采集血浆、十二指肠、空肠、回肠和结肠进行研究。束缚应激的孕鼠血浆中 CRH、促肾上腺皮质激素（ACTH）和皮质醇（COR）水平明显升高。与 CRH 水平升高一致，我们观察到肠道氧化应激水平增强，导致肠道黏膜损伤，包括肠道形态受损、杯状细胞和增殖细胞核抗原阳性细胞数量减少、MUC2 和紧密连接表达减少，以及 CRHR1 和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）表达增加。此外，外源性 CRH 可通过 CRHR1 直接促进 IPEC-J2 细胞凋亡，并影响其细胞周期（S 和 G2 期），而 antalarmin 可减轻这种现象。因此，我们的研究结果表明，束缚应激导致了孕巴马小型猪的肠道功能障碍，这些变化与肠道中 CRH 和 CRHR1 的表达增强有关。
