同种大鼠心脏移植急性排斥反应时诱生型一氧化氮合酶活性的实验研究

Experimental Study on the Activity of Inducible Nitric Oxide Synthase in the Acute Cardiac Aallograft Rejection of Rats.

目的 :观察同种大鼠心脏移植急性排斥反应时诱生型一氧化氮合酶 ( i NOS)活性 ,及氨基胍 ( AG)与环孢素 A( Cs A)对其影响。方法 :同种大鼠心脏移植动物模型 ,于术后 4d处死对照组、AG与高、低剂量 Cs A处理组的移植鼠 ,测血清 NO含量、心肌 i NOS活性及进行移植物病理分析。结果 :对照组 i NOS活性及其移植物排斥反应等级均显著高于各处理组 ( P<0 .0 5) ;AG与 Cs A对i NOS活性、NO产生有抑制作用 ,并相应地缓解急性排斥反应。结论 :同种移植急性排斥反应早期移植物即有 i NOS表达与 NO产生 ,NO参与排斥反应 ;Cs A抑制 NO产生可能为其抗急性排斥作用的机制之一。

Objective: To investigate the activity of inducible nitric oxide synthase (iNOS), and the effect of aminiguanidine(AG) and cyclosporine A (CsA) on iNOS in the acute cardiac allograft rejection of rats. Methods: Allegeneic (Wistar donor to SD recipient) heterotopic intraabdominal cardiac transplantation was performed according to Ono's method. In addition to the control group, other three groups were treated by AG (600 mg/kg/d), low dose CsA(2 mg/kg/d) and high dose CsA (10 mg/kg/d). All animals were sacrificed to obtain grafted heart and serum on postoperative day 4. iNOS activity of allografts and serum NO were detected. Histological grade of acute rejection was also examined. Results: iNOS activity and serum NO level and histological grade of acute rejection in the control group were higher than those in all treated groups. AG and CsA significantly reduced the activity of iNOS and NO production, and alleviated histological grade of acute allograft rejection. Conclusion: The inhibition of iNOS activity and NO production by CsA might be one of mechanisms by which CsA exerts the effct of immunosuppression in acute allograft rejection.