环孢素A对大鼠肝移植后iNOS及INF-γ基因转录

Effects of cyclosporine A on iNOS and IFN-γ gene transcriptions after orthotopic liver transplanted in rats

目的了解肝移植后干扰素-γ(IFN-γ)和诱导型一氧化氮合酶(iNOS)基因表达变化,以及环孢素A(CsA)对IFN-γ和iNOS基因转录的调节作用。方法采用大鼠原位肝移植模型,用半定量RT-PCR方法,分别测定移植后1,3,5,7和12d时Wistar→Wistar肝移植对照组、SD-Wistar肝移植组、SD-Wistar肝移植+CsA治疗组〔3.0mg/(kg·d)肌注〕肝组织中IFN-γmRNA和iNOSmRNA。结果大鼠原位肝移植后不同时间内,Wistar→Wis tar肝移植组肝组织中IFN-γmRNA和iNOSmRNA水平均较低;SD→Wistar肝移植组肝组织中,IFN-γmRNA和iNOSmRNA水平均明显升高(P<0.05);与SD→Wistar肝移植组比较,SD→Wistar肝移植+CsA治疗组大鼠肝组织中IFN-γ和iNOS基因转录受到明显抑制(P<0.05)。上述IFN-γmRNA和iNOSmRNA水平变化之间均具有良好的相关性(r=0.765,P<0.05)。结论IFN-γmRNA和iNOSmRNA水平与原位肝移植后排斥反应程度密切相关,CsA抗移植物排斥反应的机制与其下调IFN-γ和iNOS基因转录有关。

Objective To determine changes of IFN-γ and iNOS genes expressions, and the effect of cyclosporine A （CsA） on regulating the transcription of IFN-γ and iNOS genes. Methods By using orthotopic liver transplantation rat mod- el and semi-quantitative RT-PCR, IFN-γ mRNA and iNOS mRNA levels in the liver tissues of the rats in Wistar→Wistar liver transplantation group, SD→Wistar liver transplantation group and SD→Wistar liver transplantation plus CsA treatment group[3.0 mg/（kg·d）, im] on the 1st, 3rd, 5th, 7th and 12 th day after transplantation. Results In the different periods after the orthotopic liver transplantation, all the IFN-γ mRNA and iNOS mRNA levels of the liver tissues in Wistar-Wistar liver transplantation group were relative low. In the liver tissues of rats in SD→Wistar liver transplantation group, all the IFN-γ mRNA and iNOS mRNA levels were remarkably increased （P〈 0.05）. In comparison with the detection results from SD→Wistar liver transplantation group, the transcription of IFN-γ and iNOS genes in the liver tissues of rats in SD→Wistar liver transplantation plus CsA treatment group were obviously inhibited （P〈0.05）. The changes between IFN-γ mRNA and iNOS mRNA levels mentioned above showed fine correlation（ r=0. 765, P〈0.05 ）. Conclusion The IFN-γ mRNA and iNOS mRNA levels are closely associated with the reject reaction after orthotopic liver transplantation. The mechanism of CsA against graft-reiection may be relative to its down-regulation of IFN-γ and iNOS gene transcriptions.