Dong Yulan, Han Yanan, Wang Zixu, Qin Zhuoming, Yang Chenyu, Cao Jing, Chen Yaoxing
Laboratory of Veterinary Anatomy, College of Animal Medicine, China Agricultural University, Haidian, Beijing, 100193, People's Republic of China.
Institute of Poultry, Shandong Academy of Agricultural Sciences, Jinan, 250100, China.
BMC Gastroenterol. 2017 Jun 21;17(1):82. doi: 10.1186/s12876-017-0634-5.
During weaning, babies and young animal often experience diarrhea from food intolerance and/or decreasing levels of maternal antibodies, and diarrhea tends to be particularly severe during the early-weaned period, which often exhibits an underdeveloped immune system, a disturbed gut environment and results in nutrient malabsorption and dehydration. It was deduced that neuroendocrine might have close relation with diarrhea, especially 5-HT.
To explore the role of serotonin (5-HT) in weaning mice subjected to stress-induced diarrhea, 21-day-old weaned mice were divided into the following groups: control group, stress-induced diarrhea group (restrained by binding the hind limbs and intragastric administration of folium sennae with 0.4 g/mL, 15 mL/kg body weight) and para-chlorophenylalanine (PCPA) + stress-induced diarrhea group (30 mg/mL, 300 mg/kg body weight PCPA intraperitoneal injection before stress-induced diarrhea treatment).
Based on results from enzyme-linked immunosorbent assays, histological staining, lymphocyte proliferation assays and flow cytometry analysis, we found that the mice experienced increases in several stress markers, which coincided with severe diarrhea and an increase in 5-HT levels. However, pre-treatment with PCPA resulted in a decrease in the stress indicators and the severity of diarrhea, which correlated with decreased 5-HT levels. Interestingly, stress-induced diarrhea caused changes in various aspects of the immune system, including the amount of intraepithelium lymphocytes, CD4/CD8 T lymphocyte populations, B and T lymphocyte proliferation, and the secretion of sIgA and cytokines in the small intestine and ileum. However, these immune system changes could be reversed upon treatment with PCPA.
We observed a distinct correlation between 5-HT levels and the occurrence of stress-induced diarrhea in weaning mice, which may result in the deregulation of the mucosal immune system.
在断奶期间,婴儿和幼小动物常因食物不耐受和/或母体抗体水平下降而出现腹泻,且腹泻在早期断奶阶段往往尤为严重,此时免疫系统发育不全,肠道环境紊乱,会导致营养吸收不良和脱水。据推测,神经内分泌可能与腹泻密切相关,尤其是5-羟色胺(5-HT)。
为探究血清素(5-HT)在断奶应激性腹泻小鼠中的作用,将21日龄断奶小鼠分为以下几组:对照组、应激性腹泻组(通过束缚后肢并灌胃给予0.4 g/mL番泻叶,15 mL/kg体重)和对氯苯丙氨酸(PCPA)+应激性腹泻组(在应激性腹泻处理前腹腔注射30 mg/mL、300 mg/kg体重的PCPA)。
基于酶联免疫吸附测定、组织学染色、淋巴细胞增殖测定和流式细胞术分析结果,我们发现小鼠的几种应激标志物增加,这与严重腹泻和5-HT水平升高一致。然而,PCPA预处理导致应激指标和腹泻严重程度降低,这与5-HT水平降低相关。有趣的是,应激性腹泻导致免疫系统各方面发生变化,包括小肠和回肠上皮内淋巴细胞数量、CD4/CD8 T淋巴细胞群体、B和T淋巴细胞增殖以及sIgA和细胞因子的分泌。然而,这些免疫系统变化在用PCPA治疗后可逆转。
我们观察到断奶小鼠中5-HT水平与应激性腹泻的发生之间存在明显相关性,这可能导致黏膜免疫系统失调。