IL-10在炎症性肠病大鼠脑、结肠组织中表达的研究
摘要
炎症性肠病(IBD)是一类重要的肠道疾病,临床症状多变,治疗效果差,易复发,其病因和发病机制到目前为止仍不是十分明确。我们从神经-内分泌-免疫网络与机体免疫稳态调节的角度出发,探讨IL-10在IBD发生、发展中的作用,以期为探讨IBD的发生、发展及其与神经-内分泌-免疫网络的关系奠定基础。本实验以建立炎症性肠病大鼠动物模型为出发点,并且分别于造模后第3天、7天、14天、21天、28天取大鼠脑组织、结肠组织和血液。结合炎症性肠病各时期病理组织学变化,利用免疫组化方法研究脑组织、结肠组织中IL-10表达的变化,利用ELISA方法检测血清中IL-10浓度的变化。结果表明,随着肠管病理变化的加剧,IL-10在大脑皮层和下丘脑的表达升高,而在结肠组织中的表达和在血清中的浓度逐渐降低;随着肠管病理变化的减轻,IL-10在大脑皮层和下丘脑的表达逐渐降低,同时,在结肠组织中的表达和血清中的浓度逐渐升高并趋向于正常。提示脑组织中IL-10的变化与IBD的发生、发展呈正相关;而结肠组织和血清中IL-10的变化与IBD的发生、发展呈负相关。研究结果提示,IL-10作为神经-内分泌-免疫网络中共用的信息分子可能在IBD的发生、发展中起着重要作用。
Inflammatory bowel disease (IBD) is an important intestinal disease, including the crohn disease (CD) and ulcerative colitis (UC).There is a great diversity of clinical symptom, a bad therapeutic efficacy and an easy recidivism. Especially in Europe and the America, it gets a high morbility, simultaneously, the morbility is increasing gradually in recent years. The etiopathogenisis and nosogenesis are unclear now. Most researchers think they are related with infection, immunologic abnormality, heredity and so on. Immunologic abnormality is considered to play the most important role among all of these factors.T cells play an extremely important role in the immune system. According to the difference of cytokines that CD4 +T cell secretes and mediating immune function, they are divided into Th1 and Th2, Th1 cells express IFN-γand IL-2 mainly, and Th2 cells express IL-4, IL-5 and IL-10 etc. More and more evidences prove that Th1 and Th2 have different roles in the course of mediating immune response. Th1/Th2 imbalance has been considered to be one of the pathogenesis of IBD. When Th1 or Th2 cells enhance mucosa inflammatory response, the amount of the suppression cells, regulatory T cells and the secretion of cytokines decreased significantly, which demonstrated in the development of inflammatory bowel disease the imbalance plays an important role. In short, both T cells and their sub-type (Th1,Th2,Th3) and cytokines (pro-inflammatory cytokines, anti-inflammatory cytokines and growth factor) play a significant role in the pathogenesis course of IBD immunity.
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. Since the occurrence and development of IBD are closely related to T cells and their cytokines, the nerve - endocrine - immune regulatory network plays an important role in regulating T-cell-mediated immunity. However, whether the nerve-endocrine-immune regulatory network mediates the development and occurrence of IBD, few are reported today.
In view of the above, the experiment is to use artificially induced IBD rats as models, make use of immunohistochemical method, to discuss the effect and mechanism of IL-10 in the occurrence and development of IBD, from the view of the nerve-endocrine-immune network and the immune homeostasis regulation. It will lay a strong foundation to ensure the relationship of the course of IBD and neuroendocrine immune network, provide a new way to prevent and treat the inflammatory bowel disease (IBD) , and offer experimental basis for further study at nerve endocrine immune network theory. Therefore, we make IBD models by giving an enema with trinitro-benzene-sulfonic acid. Put the IBD rats to death on the 3rd ,7th ,14th ,21st, 28th day. Take the brain and colon tissues. Detect the expression level of IL-10 in the intestinal canal and brain by immunohistochemistry and acquire the concentration of IL-10 in the serum by ELISA. Results show, with the development of IBD, there is a lower expression level of IL-10 in the colon. When rats recover, the expression level of IL-10 increases gradually, and finally reach the normal level. At the same time, the expression level of IL-10 in the cerebral cortex and hypothalamus has a opposite change during the whole process of the IBD. The concentration of IL-10 in the serum begins to lower when IBD happens, on the contrary , it begins to increase accompanied with diease recovery. The experiment shows that IBD is closely related with the activity of neuroendocrine. Immune-nerve-endocrine network may be involved in the process of the occurrence and development of IBD, and it plays a role in the pathogenesis of IBD. Experiment provides a theoretical basis for the study of pathogenesis.
Inflammatory bowel disease (IBD) is an important intestinal disease, including the crohn disease (CD) and ulcerative colitis (UC).There is a great diversity of clinical symptom, a bad therapeutic efficacy and an easy recidivism. Especially in Europe and the America, it gets a high morbility, simultaneously, the morbility is increasing gradually in recent years. The etiopathogenisis and nosogenesis are unclear now. Most researchers think they are related with infection, immunologic abnormality, heredity and so on. Immunologic abnormality is considered to play the most important role among all of these factors.T cells play an extremely important role in the immune system. According to the difference of cytokines that CD4 +T cell secretes and mediating immune function, they are divided into Th1 and Th2, Th1 cells express IFN-γand IL-2 mainly, and Th2 cells express IL-4, IL-5 and IL-10 etc. More and more evidences prove that Th1 and Th2 have different roles in the course of mediating immune response. Th1/Th2 imbalance has been considered to be one of the pathogenesis of IBD. When Th1 or Th2 cells enhance mucosa inflammatory response, the amount of the suppression cells, regulatory T cells and the secretion of cytokines decreased significantly, which demonstrated in the development of inflammatory bowel disease the imbalance plays an important role. In short, both T cells and their sub-type (Th1,Th2,Th3) and cytokines (pro-inflammatory cytokines, anti-inflammatory cytokines and growth factor) play a significant role in the pathogenesis course of IBD immunity.
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. Since the occurrence and development of IBD are closely related to T cells and their cytokines, the nerve - endocrine - immune regulatory network plays an important role in regulating T-cell-mediated immunity. However, whether the nerve-endocrine-immune regulatory network mediates the development and occurrence of IBD, few are reported today.
In view of the above, the experiment is to use artificially induced IBD rats as models, make use of immunohistochemical method, to discuss the effect and mechanism of IL-10 in the occurrence and development of IBD, from the view of the nerve-endocrine-immune network and the immune homeostasis regulation. It will lay a strong foundation to ensure the relationship of the course of IBD and neuroendocrine immune network, provide a new way to prevent and treat the inflammatory bowel disease (IBD) , and offer experimental basis for further study at nerve endocrine immune network theory. Therefore, we make IBD models by giving an enema with trinitro-benzene-sulfonic acid. Put the IBD rats to death on the 3rd ,7th ,14th ,21st, 28th day. Take the brain and colon tissues. Detect the expression level of IL-10 in the intestinal canal and brain by immunohistochemistry and acquire the concentration of IL-10 in the serum by ELISA. Results show, with the development of IBD, there is a lower expression level of IL-10 in the colon. When rats recover, the expression level of IL-10 increases gradually, and finally reach the normal level. At the same time, the expression level of IL-10 in the cerebral cortex and hypothalamus has a opposite change during the whole process of the IBD. The concentration of IL-10 in the serum begins to lower when IBD happens, on the contrary , it begins to increase accompanied with diease recovery. The experiment shows that IBD is closely related with the activity of neuroendocrine. Immune-nerve-endocrine network may be involved in the process of the occurrence and development of IBD, and it plays a role in the pathogenesis of IBD. Experiment provides a theoretical basis for the study of pathogenesis.
引文
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[3] Buer J, Lanoue A , Franzek A,et al.Interleuin 10 secretion and impaired effector function of major histocompatibility complex classⅡ-restricted T cell anergized in vivo[J].J Eur Med,1998,187,177-183
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