【作者】 王全懂；

【导师】 史中立；

【作者基本信息】 河北医科大学 ， 人体解剖学与组织胚胎学， 2004， 硕士

【摘要】 近年发现，一些非经典递质（如NO）在痛觉的调制中发挥重要作用。一氧化碳（CO）作为新型递质，与疼痛的关系尚缺乏研究。血红素氧合酶（HO）是体内产生CO的限速酶。HO-1是HO的诱导型。除个别脑区外，神经系统在生理状态下不表达HO-1。新近发现，外周器官创伤可启动脑组织表达HO-1，提示HO-1/CO与伤害刺激信息的调制有联系。神经系统哪些部位通过诱导HO-1/CO参与痛觉调制，尚缺乏系统的形态学研究。目的：观察疼痛诱导大鼠神经系统表达HO-1的组织分布，以确定神经系统哪些部位通过诱生CO参与痛觉调制。方法：通过足底注射福尔马林的方法复制大鼠炎性疼痛模型，用免疫组织化学染色方法，观察疼痛诱导神经系统表达HO-1的组织分布。健康SD雄性大鼠18只，随机分为正常组和疼痛组（n=9）。在右后掌皮下注射5%福尔马林溶液0.2ml，复制大鼠炎性痛模型。注射12 h后，在麻醉状态下经左心室行主动脉插管，灌注4 %多聚甲醛溶液250ml (0.1M PBS配制，pH7.4)。取腰骶背根节、腰骶段脊髓、脑干、间脑及端脑。将标本做横断切片，用抗大鼠HO-1抗体进行免疫组织化学染色，光镜观察并照相。结果：①正常成年大鼠脊髓前角灰质、红核、动眼神经核及丘脑网状核等区域有少量散在分布的HO-1阳性神经<WP=4>元。②在炎性疼痛刺激诱导下，背根节、脊髓灰质、脑干网状结构、中脑中央灰质、黑质、室旁核、视上核、尾壳核、隔核、额顶叶皮质神经元及腰骶髓白质内的角质细胞表达HO-1。结论：在外周炎性疼痛刺激作用下，神经系统的背根节、脊髓灰质、延髓网状结构、中脑中央灰质、额顶叶皮质等与痛觉调制有密切关系的部位，以及与应激反应相关的神经内分泌核团视上核、室旁核表达HO-1。据此推定，HO-1/CO在上述神经部位参与了痛感觉及痛反应的调制。更多还原

【Abstract】 Although it has been discovered that some nontraditional transmitter ( such as NO) played an important role in the modulation of algaesthesis, the effect of carbon monoxide (CO), a newly found transmitter, in algaesthesis has not yet been fully demonstrated. Heme oxygenase (HO) is the rate-limiting enzyme of the CO production, and HO-1 is the induced form of HO. Under normal conditions, HO-1 can not be found in the nervous system physiologically except for some special areas. According to the recent studies, the trauma of peripheral organs can induce the expression of HO-1 in the brain tissue, which indicated that there might be some relationship between HO-1/CO and the modulation of injury stimulus. But the morphological study about which part in the nervous system getting involved is still unclear.Objective: To observe the changes and distribution of HO-1 expression in rat nervous system following inflam- matory pain, and elucidate which part in the nervous system relates to the modulation of pain.Methods: The model of inflammatory pain of rats was made by the subcutaneous injection of formalin solution. The tissue distribution of the HO-1 expression induced by pain in the <WP=6>nervous system was investigated by immunohistochemi- stry. Eighteen healthy SD rats were divided into two groups randomly: the control group and the pain group (n=9 in both groups), then the model was made by injecting formalin solution (0.2 ml, 5% ) to the right hind paw of rats. After 12 hours, rats were anesthetized, then perfused and fixed through the ascending aorta of heart with 250 ml, 4 % citromint ( prepared by 0.1M PBS, pH=7.4) . After that, the dorsal root ganglion of lumboscsaral segment, spinal cord of lumboscsaral segment, brain stem, diencephalons and telencephalon were taken out respectively. Coronal sections of the different samples were cut and stained by anti-HO-1 antibody of rats using immunohistochemistry, then observed under light microscope and photographed. Results: 1. HO-1 positive signals could be found scattering in the gray matter of spinal cord, red nucleus, nucleus of oculomotor nerve and thalamic reticular nucleus in the normal rats. 2. HO-1 expression could be induced by inflammatory pain stimulus in doral root ganglion, gray matter of spinal cord, reticular formation of brain stem, periaqueductal gray, substantia nigra, hypothalamic paraventricular nucleus and supraoptic nucleus, caudate- putamen, septal nucleus, area of frontal and parietal cortex and neuroglial cells of white matter of lumboscaral segment.Conclusions: Peripheral inflammatory pain can induce the expression of HO-1 in dorsal root ganglion, gray matter of <WP=7>spinal cord, reticular formation of medulla oblongata, periaqueductal gray, area of frontal cortex etc which have close relationship to the modulation of pain, together with some stress-related areas, such as paraventricular nucleus and supraoptic nucleus. From above It could be concluded that HO-1/CO play a role in the modulation effects on pain sense and pain reaction .更多还原