【作者】 刘冬；

【导师】 胡仲明；

【作者基本信息】 吉林大学 ， 基础兽医学， 2009， 硕士

【摘要】 疑核是重要的内脏运动核,它与中枢神经系统和外周器官建立了广泛的神经联系,并且在调节T细胞介导的免疫中发挥重要作用。炎症性肠病(IBD)是一种病因未明的慢性肠道非特异性炎症性疾病。目前认为免疫因素,特别是Th1/Th2免疫应答失衡是引起IBD发病的主要原因之一。IL-18作为一种促炎性细胞因子,主要作用于Th1细胞。TGF-β可由Th3细胞分泌,对维持Thl/Th2之间的平衡起重要作用。为了探讨IBD与细胞因子TGF-β、IL-18之间的关系,以及疑核是否与IBD有着重要联系,本实验从神经-内分泌-免疫网络与机体免疫稳态调节的角度出发,采用Real-Time PCR和ELISA方法,利用疑核定位技术,检测急性电刺激疑核前后,细胞因子TGF-β和IL-18在TNBS诱导的IBD大鼠结肠、胸腺、脾脏、外周血淋巴细胞中mRNA水平的变化和血清中蛋白浓度的变化。研究结果表明,急性电刺激IBD大鼠疑核后TGF-β、IL-18 mRNA表达水平在结肠、脾脏和外周血淋巴细胞中均显著高于对照组和假刺激组;而在胸腺中TGF-βmRNA表达降低,IL-18 mRNA表达增加。急性电刺激IBD大鼠疑核后血清中TGF-β、IL-18蛋白浓度均显著高于对照组和假刺激组。研究结果提示,疑核可能通过对IBD相关细胞因子TGF-β、IL-18的调控,介导IBD的发生、发展过程,从而对IBD发生、发展发挥调节作用。更多还原

【Abstract】 Nervous, endocrine and immune form a complex network, named neuro-endocrine-immune regulatory network, which controls the body’s various vital movement, maintains homeostasis of the body. When the homeostasis is disrupted, certain parts in the network will respond and do some change in the function, meanwhile, some change occurs in the referred network, leading to certain diseases and the emergence of pathological process. Neuro-endocrine-immune disorder is a common feature of all the diseases. All the clinical diseases have a nerve-endocrine-immune disorder. The disease process is actually a kind of disorder for homeostasis regulation of nerve-endocrine-immune network, however, among the nerve, endocrine and immune disorders, immune disorder is principal.Ambiguous nucleus (Amb), belonging to nucleus nervi vagi,is a special nervus visceralis motor nucleus.The Amb lies in oblongata ventrolateral formatio reticularis and involves a variety of neurons,such as adrenergic neuron, cholinergic neuron, peptidergic neuron. The Amb has a widespread nerve touch with CNS and periphery orgns and plays an important role in T-cell mediated immunity. Above all, the Amb plays a key role in the neuro-endocrine-immuno- regulatory network.Inflammatory bowel disease (IBD) is a group of unknown etiology, chronic inflammatory diseases involving in the gastrointestinal tract, including chronic nonspecific ulcerative colitis (UC) and Crohn’s disease (CD). The distribution of the disease is world-wide, and it seriously endangers the health of our people, and recently its incidence rate is increasing. The etiology and pathogenesis of IBD are not very clear yet. The majority of researches suggest that IBD is a kind of autoimmune disease caused by the interaction of many factors.Among all of these, immunity plays a vital role in the occurrence and development of IBD. Many research datas show that its pathogenesis is auto-immune abnormality referring to a variety of cytokines, eventually resulting in tissue damage. The imbalance of Th1/Th2 immune response and the imbalance between pro-inflammatory cytokines and anti-inflammatory cytokines play an important role in the pathogenesis of IBD. IL-2 and IFN-γare pro-inflammatory cytokines secreted by Th1 cells and have wide immuno-regulation role and play a significant role in the regulation of cytokine network..IL-18 is a kind of pro-inflammatory cytokines mainly produced by Th1 cells.TGF-βis a kind of growth factor, which has bidirectional regulatory function and has a wide range of biological effects. Its production is closely related with Th3. They play an important role in the regulation of cytokine network and have a broad immune regulatory role.Therefore, we made use of TNBS-induced IBD rats as models and the technology of Amb localization, to detect whether acute electric stimulation Amb in IBD rats will influence TGF-β,IL-18 mRNA in colon,thymus,spleen and lymphocytes by Real-time PCR and whether acute electric stimulation Amb in IBD rats will influence the concentration of TGF-β,IL-18 in serum by ELISA. We found that the mRNA of IL-18 was obviously increasing in colon,thymus,spleen and peripheral-blood lymphocyte after the effective electric stimulation Amb of IBD rats in comparison with those sham-stimulated rats and those matching control rats, the mRNA of TGF-βwas also obviously increasing in colon,spleen and peripheral-blood lymphocyte after the effective electric stimulation Amb of IBD rats in comparison with those sham-stimulated and matching control rats, but the mRNA of TGF-βwas decreased in thymus. The concentration of TGF-β,IL-18 in serum was significantly increasing after the effective electric stimulation Amb of IBD rats in comparison with those sham-stimulated and matching control rats. This demonstrates Amb has an positive regulation to IL-18, mainly has an has an positive regulation to TGF-β,but has a negative regulation in the thymus in IBD.This result reveals that: neuro-endocrine-immune regulatory network participate in the occurrence ang development of IBD, Amb has a certain regulation to IBD-related cytokines,may mediates the occurrence and development of IBD, and may play an important role in the occurrence ang development of IBD.更多还原