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[小肠同种异体移植排斥反应中的移植物内mRNA表达]

[Intragraft mRNA expression in small intestinal allograft rejection].

作者信息

Li Y, Li N, Li J

机构信息

Institute of Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002.

出版信息

Zhonghua Yi Xue Za Zhi. 1999 Oct;79(10):773-6.

Abstract

OBJECTIVE

To investigate the changes of intragraft mRNA expression of IL-2, IFN-gamma, perforin, granzyme B during small intestinal allograft rejection in rats.

METHODS

Heterotopic small intestinal transplantation was performed with inbred rat F344/N(RT1(1)) and inbred rat Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups; group I, Wistar; group II, Wistar-->Wistar; group III, F344-->Wistar; and group IV, F344-->Wistar + cyclosporine A(6 mg/kg.d-1). The grafts were harvested on POD 3, 5 and 7, All graft samples were examined histologically. The intragraft mRNA expression of IL-2, IFN-gamma, perforin and granzyme B was determined.

RESULTS

  1. The histological examination showed that mild acute rejection occurred on POD 3 in group III, moderate acute rejection on POD 5, severe acute rejection on POD 7, while none of group II had histologic evidence of acute rejection. The histologic evidence of group IV indicated that cyclosporine A could effectively controll acute allograft rejection. 2. The gene expression was almost negative in group I. Only on POD 5 was the IL-2 mRNA expression of group III significantly higher than that of group II (P < 0.05). The IFN-gamma mRNA expression of group III was significantly higher than that of group II and group IV (P < 0.01) on POD 3, 5 and 7. The level of perforin and granzyme B mRNA expression was significant higher in group III than in the other two control groups only on POD 5 and POD 7.

CONCLUSIONS

IL-2, IFN-gamma, perforin and granzyme B play important roles in small intestinal allograft rejection. Detection of these molecules gene expression with RT-PCR, especially the gene expression of IFN-gamma, perforin and granzyme can become an early, specific, sensitive and clinically valuable diagnostic tool for small intestinal allograft rejection. Furthermore, anti-rejection therapy or induction of immune tolerance could be achieved by breaking down these molecules gene transcription.

摘要

目的

研究大鼠小肠移植排斥反应过程中移植肠内白细胞介素-2(IL-2)、γ干扰素(IFN-γ)、穿孔素、颗粒酶B的mRNA表达变化。

方法

采用近交系大鼠F344/N(RT1(1))和近交系大鼠Wistar/A(RT1-Ak,RT1-Ed)进行异位小肠移植。所有受体分为四组:Ⅰ组,Wistar大鼠;Ⅱ组,Wistar→Wistar大鼠;Ⅲ组,F344→Wistar大鼠;Ⅳ组,F344→Wistar大鼠+环孢素A(6mg/kg·d-1)。于术后第3、5、7天取移植肠,所有移植肠样本进行组织学检查,并测定移植肠内IL-2、IFN-γ、穿孔素和颗粒酶B的mRNA表达。

结果

  1. 组织学检查显示,Ⅲ组术后第3天发生轻度急性排斥反应,第5天为中度急性排斥反应,第7天为重度急性排斥反应,而Ⅱ组无急性排斥反应的组织学证据。Ⅳ组的组织学证据表明环孢素A可有效控制急性移植排斥反应。2. Ⅰ组基因表达几乎为阴性。仅在术后第5天,Ⅲ组的IL-2 mRNA表达显著高于Ⅱ组(P<0.05)。术后第3、5、7天,Ⅲ组的IFN-γ mRNA表达显著高于Ⅱ组和Ⅳ组(P<0.01)。仅在术后第5天和第7天,Ⅲ组的穿孔素和颗粒酶B mRNA表达水平显著高于其他两个对照组。

结论

IL-2、IFN-γ、穿孔素和颗粒酶B在小肠移植排斥反应中起重要作用。应用逆转录聚合酶链反应(RT-PCR)检测这些分子的基因表达,尤其是IFN-γ、穿孔素和颗粒酶的基因表达,可成为小肠移植排斥反应早期、特异、敏感且具有临床价值的诊断工具。此外,通过阻断这些分子的基因转录可实现抗排斥治疗或诱导免疫耐受。

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