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Rat colitis induced by intrathecal injection of substance P

LIN Ping, WU Xing-Yu, PAN Hui, JIANG Hui-Jun, MEI Lin

Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China

Abstract

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 20 μg, 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.

Key words: colitis; neurogenic inflammation; spinal cord; substance P; NK1 receptor; rats

Received: 2009-02-10　　Accepted: 2009-05-20

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Citing This Article：

LIN Ping, WU Xing-Yu, PAN Hui, JIANG Hui-Jun, MEI Lin. Rat colitis induced by intrathecal injection of substance P. Acta Physiol Sin 2009; 61 (4): 331-338 (in Chinese with English abstract).