精胺通过细胞因子促进幼龄哺乳仔猪肠道发育的机理研究

The neonatal piglet feeding imposes a severe challenge to the immaturation of gastrointestinal tract and often leads to gastrointestinal disorders and growth retardation in the swine production. It had been established that oral administration of spermine advanced intestinal maturation and growth performance of suckling piglets in the previous studies of doctor candidate by this project applicant. Moreover, the indirect effect of orally administered spermine on intestinal maturation by the stimulation of cortical release in suckling piglets was observed and was the first to report. According to this interesting finding, the hypothesis or mechanism of oral administration spermine improving the intestinal development of suckling piglet by the regulation of cytokines stimulating cortisol release is worth to study in the field of neuroendocrinology. The key of our studies in this project is focus on the intestinal immune cytokines IL-1, IL-2, IL-6, TNF-α, and IFN-γ, and the blood contents of the hormone CRH, ACTH, and cortisol are also determined. Therefore, some advanced analysis methods and technique including magnetic activated cell sorting (MACS), radioimmunodetection, and fluorescent quantitative PCR are used in our studies. The clarification of the pathway of spermine stimulating cortisol release by some preonunced cytokines from enterocytes on intestinal maturation in young piglets are the aims of our studies in this applied project. Our findings should be benefit for the advancement of neuroendocrinology, and also be valuable to be applied in the swine production.

幼龄仔猪肠道发育不健全制约生长性能是当前我国养猪业生产难题之一。项目申请人博士期间研究证明：口服精胺有效地促进哺乳仔猪肠道发育和改善了生长性能；并首次发现精胺激发肾上腺糖皮质激素分泌而促进仔猪肠道发育的作用。据此，本项目借助神经内分泌学这一新兴交叉学科的创新研究思路，综合应用免疫磁珠细胞分离法、放射免疫检测技术、荧光定量PCR等免疫学和细胞分子生物学的现代分析与检测技术，具体研究精胺对仔猪肠道免疫细胞因子和"下丘脑－垂体－肾上腺"内分泌代谢的影响，重点分析精胺对仔猪血液和肠道IL-1、IL-2、IL-6、TNF-α、IFN-γ等5个细胞因子以及CRH、ACTH、cortisol等激素的影响，揭示精胺通过肠免疫细胞分泌具体的细胞因子，激发肾上腺糖皮质激素而促进幼龄哺乳仔猪肠道发育的机理。项目研究结果不仅丰富神经内分泌学科的内涵，并在养猪业有实际的应用价值。

幼龄仔猪肠道发育不健全制约生长性能是当前我国养猪业生产难题之一。项目申请人博士期间研究证明：口服精胺有效地促进哺乳仔猪肠道发育和改善了生长性能；并首次发现精胺激发肾上腺糖皮质激素分泌而促进仔猪肠道发育的作用。据此，本项目借助神经内分泌学这一新兴交叉学科的创新研究思路，重点设计了“仔猪血浆皮质醇抑制模型”，结合体外肠粘膜上皮细胞增殖实验，探讨了精胺通过哪些具体的细胞因子、激发皮质醇分泌进而促进幼龄仔猪肠道发育的机理。结果显示：在仔猪皮质醇抑制模型下，无论是否抑制皮质醇，口服精胺仍然增加了仔猪肠道细胞因子ACTH、IL-1、IL-2、TNF-α的分泌，提高了肠粘膜上皮细胞的增殖率，对表征哺乳仔猪肠道发育的肠道形态学指标、粘膜二糖酶（麦芽糖酶比活力）指标及生产性能指标有显著促进作用。这些结果初步证明口服精胺通过3个肠道细胞因子IL-1、IL-2、TNF-α激发了皮质醇分泌进而促进幼龄乳仔猪肠道发育，实现改善幼龄哺乳仔猪的生长性能。项目研究结果不仅丰富神经内分泌学科的内涵，并在养猪业有实际的应用价值。