神經內分泌物質在後感染腸躁症小鼠之內臟高敏感性機轉中所扮演的角色

Abstract

背景 : 腸躁症是一種功能性的腸胃道失調，並且伴隨反覆性腹痛和排便習慣的改變，但卻無法確認病因的存在，而生活中的精神壓力或感染性腸胃炎後都可能誘發腸躁症，特稱作 『後感染性腸躁症』。約有40-80% 的受到梨形蟲感染病人，在排除寄生蟲後出現腹痛等腸躁症症狀。本研究的目的是利用梨形蟲感染加上壓力來建立腸躁症的小鼠模式，藉此評估其對內臟高敏感性和腸道功能的影響。 方法 : 小鼠灌食梨形蟲的滋養體或做為對照的磷酸緩衝液，並於感染後的35-44天即梨形蟲已排除體外時，給予每天一小時共十天的避水壓力（water avoidance stress, WAS）或無處理（nonhandled, NH）。有些動物組別於第44天給予腹腔注射膽囊收縮素受體拮抗劑（AIH、BIH）。藉由內臟動器對結直腸撐張（colorectal distension, CRD）來評估腹痛敏感程度，並透過 Protein Gene Product 9.5 （PGP 9.5）觀察神經纖維及測量Cholecystokinin（CCK）於腸道組織的變化。 結果 : 梨形蟲感染後排除或精神壓力之單一因子，均會導致結直腸撐張刺激下的痛覺異常與痛覺過度，且兩者合併之雙重因子對痛覺敏感化有協同效應。兩者合併之雙重因子會造成腸道黏膜神經纖維分布及CCK總量增加。而拮抗劑 AIH 、BIH 均能抑制內臟高敏感化。 結論 : 本實驗動物模式中，寄生蟲感染排除後合併精神壓力，會造成內臟高敏感化，伴隨腸道黏膜層神經纖維分布及 CCK 總量增加。此外， CCK 受體有參與內臟高敏感化的機制。

Backgrounds : Irritable bowel syndrome（IBS）is a functional gastrointestinal disorder characterized by recurrent abdominal pain associated with changes in bowel habits in absence of identifiable etiology. Onset of IBS is likely to occur after stressful events or infectious gastroenteritis termed post-infectious（PI）IBS. Up to 40-80% of the Giardia-infected patients showed abdominal symptoms consistent with IBS after eradication of parasites. The aim is to establish a PI-IBS model using post-giardiasis combined with stress to evaluate visceral hypersensitivity and gut dysfunctions. Methods : Mice were inoculated with Giardia lamblia or pair-fed with saline on day 0, and then subjected to water avoidance stress（WAS）for 1 hr/day for 10 consecutive days or nonhandled on PI day 35-44 after clearance of parasites. In some experiments, inhibitors to cholecystokinin（CCK）receptors （AIH and BIH）were intraperitoneally administered to mice on PI day 44. Abdominal pain was evaluated by visceromoter response to colorectal distension（CRD）. Intestinal tissues were immunostained with protein gene product（PGP） 9.5 for nerve fibers; cholecystokinin（CCK）levels were also measured. Results : Increased pain perception to CRD was observed in mice post-giardiasis or stress alone, and synergistic effects was seen in post-giardiasis combined with stress. Post-infection combined with stress also increased nerve fibers and CCK levels in intestinal tissues. Administration of AIH, BIH inhibited visceral hypersensitivity in mice. Conclusion : Post-infection combined with stress caused visceral hypersensitivity associated with nerve fiber outgrowth and increased CCK levels in intestinal tissues. The visceral hypersensitivity was dependent on CCK receptors.