胸腺基质淋巴细胞生成素、OX40和OX40受体在过敏性腹泻小鼠大肠黏膜中表达的关系

Expressions of thymic stromal lymphopoietin, OX40 and OX40L in the proximal colon of murine allergic diarrhea model

目的建立小鼠过敏性腹泻模型，检测其大肠黏膜中胸腺基质淋巴细胞生成素（TSLP）、OX40、OX40受体（OX40L）的表达和肠系膜淋巴结细胞培养上清中IL-_4、IFN-1的水平，分析其之间的关系，探讨TSLP、OX40、OX40L在过敏性腹泻中的作用。方法雌性BALB／c小鼠20只随机分成两组即对照组和实验组。采用酶联免疫吸附法（ELISA）检测肠系膜淋巴结细胞培养上清中IL4和IFN-1的水平，取大肠组织HE染色观察大肠组织病理改变，SP免疫组织化学技术检测TSLP、OX40、OX40L的表达。结果@HE染色结果显示：实验组比对照组小鼠结肠黏膜组织非特异性炎症反应显著，上皮排列不规则，有大量炎性细胞浸润，固有层可见大量嗜酸性粒细胞浸润；@TSLP、OX40、OX40L在过敏性腹泻小鼠大肠黏膜中的表达水平高于对照组的表达水平（t=7．07，t=7．81，t=7．79，P均〈0．01）；③Spearman等级相关分析发现TSLP、OX40、OX40L三者问表达强度存在正相关（r=0．889，r=0．932，r=0．943，P均〈0．01），同时三者与肠系膜淋巴结细胞培养上清中IL4水平呈正相关（r=0．891，r：0．936，r=0．886，P均〈0．05），而与IFN-1水平呈负相关（r=-0．829，r=-0．881，r=-0．937，P均〈0．05）。结论TSLP、OX40、OX40L三者间表达存在正相关，并诱导了Th1／Th2轴向Th2轴漂移，促进了过敏性腹泻的发生发展。

Objective To analyse TSLP, OX40 and OX40L expression levels in coton mmcosa of allergic cliarrhea mice. Methods Female BALB/c mice were randomly divided into two groups： control group and experimental group. ELISA was employed to measure the levels of IL-4 and IFN-γ in cell culture supernarants of MLN. Proximal colon was stained by HE to assess the pathological changes of colons in both groups. The expressions of TSLP, OX40 and OX40L in colons of both groups were examined by immunohistochemistry. Results ①HE staining of proximal colon showed that nonspecific inflammation reaction, the disorganized epithelial lells and the accumulation of inflammatory cells in the lamina propria of colon were significantly increased in experimental group than that in control group. Eosinophil infiltration was more evident in experimental group. ②Immunohistoehemistry staining of colon sections showed that TSLP, OX40 and OX40L expressions in experimental group were sinificantly higher than that in control group （ t = 7. 07, t = 7.81, t = 7.79, P 〈 0.01 ）. ③Spearman correlation analysis showed that expressions of TSLP, OX40 and OX40L were positively correlated with one another（r =0. 889,r =0. 932,r =0. 943 ,P 〈0. 01 ） ; they were positively correlated with IL-4 in cell culture of supernatants of MLN （ r = 0. 891, r = 0. 936, r = 0. 886, P 〈 0. 05 ） and were negatively correlated with IFN-γ in cell culture of supernatants of MLN （r = -0. 829, r = -0. 881, r = -0. 937, P 〈 0.05 ）. Conclusion The expressions of TSLP, 0）（40 and OX40L were positively correlated with one another which contributes the Th1/Th2 axis imbalance and promotes the development of allergic diarrhea.