Gregory C R, Cooke J P, Patz J D, Berryman E R, Shorthouse R, Morris R E
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616-8745, USA.
J Heart Lung Transplant. 1996 Jan;15(1 Pt 1):58-66.
Nitric oxide suppresses proliferation and function of T cells and inhibits proliferation of smooth muscle cells in vitro and in vivo. The purpose of this study was to determine whether nitric oxide, stimulated by means of the oral administration of L-arginine, would reduce the degree of intimal thickening produced by immune injury in rat arterial allografts.
Orthotopic femoral artery transplantation was done with Brown Norway donors and Lewis recipients. Seven days before operation, and for 39 additional days, one group received 2.25% L-arginine and one group received 0.01% N-omega-nitro-L-arginine in tap water; one group received tap water only. Forty days after operation, all arterial segments were excised and examined by histopathologic, morphometric, and immunohistochemical assays.
There was no difference in the rejection response or degree of intimal thickening among the three groups. There were no qualitative differences in numbers of T cells, macrophages, or smooth muscle cells in the neointima, media, or adventitia among the untreated and treated groups. Induced nitric oxide synthase was present in the media and adventitia of the allograft vessels, but not in native rat arteries.
Enhanced production of nitric oxide, via the administration of L-arginine, has been shown to reduce tissue pathologic changes in models of mechanical or dietary injury. Enhanced nitric oxide production did not suppress rejection or inhibit intimal thickening in this model of immune-mediated injury.
一氧化氮在体外和体内均可抑制T细胞的增殖和功能,并抑制平滑肌细胞的增殖。本研究的目的是确定通过口服L-精氨酸刺激产生的一氧化氮是否会减轻大鼠动脉同种异体移植中免疫损伤所导致的内膜增厚程度。
采用Brown Norway大鼠作为供体、Lewis大鼠作为受体进行原位股动脉移植。在手术前7天以及术后另外39天,一组大鼠饮用含2.25% L-精氨酸的自来水,一组饮用含0.01% N-ω-硝基-L-精氨酸的自来水,一组仅饮用自来水。术后40天,切除所有动脉段,通过组织病理学、形态计量学和免疫组织化学分析进行检查。
三组之间的排斥反应或内膜增厚程度没有差异。未处理组和处理组的新生内膜、中膜或外膜中T细胞、巨噬细胞或平滑肌细胞的数量在定性上没有差异。诱导型一氧化氮合酶存在于同种异体移植血管的中膜和外膜中,但在正常大鼠动脉中不存在。
在机械性或饮食性损伤模型中,通过给予L-精氨酸增强一氧化氮的产生已被证明可减轻组织病理变化。在这个免疫介导损伤模型中,增强一氧化氮的产生并未抑制排斥反应或内膜增厚。