脊髓蛛网膜下腔注射P物质引起大鼠结肠炎(英文)  

Rat colitis induced by intrathecal injection of substance P

作　　者：林萍[1] 吴星宇[1] 潘慧[1] 蒋惠君[1] 梅林[1] 

机构地区：[1]北京大学医学部生理学与病理生理学系,北京100191

出　　处：《生理学报》2009年第4期331-338,共8页Acta Physiologica Sinica

基　　金：supported by Beijing Natural Science Foundation,China(No.7063083)

摘　　要：本实验从神经源性炎症的角度探讨结肠炎(colitis)发病的机理,并为神经源性结肠炎的假说提供直接的证据。健康雄性Sprague-Dawley大鼠(180～220g)经水合氯醛腹腔麻醉后,将PE-10管插入脊髓蛛网膜下腔达T12～L5水平。鞘内(intrathecal,ith)注射P物质(substance P,SP),每天一次,共14天。神经激肽-1(neurokinin-1,NK1)受体拮抗剂([D-Pro2,D-Trp7,9]-SP,22.4μg)于每次ith注射SP前10min ith预处理。观察疾病活动指数(disease active index,DAI)、结肠和脊髓组织的大体/镜下病理、以及移动抑制因子(migration inhibitory factor,MIF)蛋白的表达。结果显示:ith注射SP 10μg和20μg能够引起大鼠DAI明显升高、结肠组织炎性细胞浸润、腺体萎缩和MIF高表达(与生理盐水组相比,P<0.05,P<0.01);但在脊髓,仅在ith注射SP 20μg组见到轻度充血水肿,并无明显神经元坏死。NK1受体拮抗剂预处理,能够延长ith注射SP 20μg后DAI开始升高的潜伏期、减小DAI升高的幅度、抑制MIF在结肠组织的高表达。上述实验结果表明,ith注射SP能够引起大鼠结肠炎,该效应是通过激活脊髓NK1受体实现的,肠组织的MIF参与了此炎症过程。脊髓高浓度SP能通过NK1受体介导结肠炎这一发现可能具有潜在的临床意义。The aim of this study was to, from the point of neurogenic inflammation, explore the pathogenesis of colitis and to provide direct evidence for the neurogenic colitis hypothesis. Male Sprague-Dawley rats （180-220 g） anesthetized with chloral hydrate were intrathecally （ith） implanted with polyethylene-10 （PE-10） catheter to reach the spinal cord T12-L5 level. Substance P （SP） was ith injected once a day for 14 d. The disease active index （DAI） score was calculated by rat body weight and stool. The macroscopic and HE staining-microscopic pathologies of colon/spinal tissue were evaluated. By immunofluorescence staining, the protein expression of a pro-inflammatory cytokine, migration inhibitory factor （MIF）, in colon tissue was detected and was semi-quantitatively analyzed. The results showed that in the colon tissue, inflammation was dose-dependently aggravated by ith SP 10 μg and 20μg, whereas in the spinal tissue, only slight edema and congestion were seen in SP 20 μg group. The MIF protein of colon tissue was increased in ith SP 10 μg and 20 μg groups （P〈0.05, P〈0.01 as compared to normal saline group respectively）, but in the spinal tissue, there was no obvious MIF protein expression either in SP groups or in normal saline group. Pretreatment with neurokinin-1 （NK1） receptor antagonist （[D-Pro2, D-Trp7, 9] -SP, 22.4 μg, ith, 10 min before ith SP） prolonged the latency of DAI rising and reduced the DAI amplitude, as well as prevented the high MIF expression induced by ith SP. These results suggest that rat colitis can be induced by direct SP stimulation in lumbar spine via activating central NK1 receptor; and that colonic MIF is possibly one of the inflammatory factors involved in this pathogenesis. These data provide a reasonable support to the hypothesis of colitis being a neurogenic inflammation. In addition, a potential clinical significance for the finding that higher concentration of spinal SP can induce colitis via NK1 receptor is discussed.

关 键 词：结肠炎 神经源性炎症 脊髓 P物质 神经激肽-1受体 大鼠 

分 类 号：R574.6[医药卫生—消化系统]