Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy.
Structural and functional evolution of jejunal allograft rejection in rats and the ameliorating effects of cyclosporine therapy.
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大鼠空肠同种异体移植排斥的结构和功能演变以及环孢素治疗的改善作用。
DOI：
10.1172/jci111726
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Kirkman,RL
中科院分区：
文献类型：
--
作者：
Madara,JL;Kirkman,RL
我们利用1微米切片、电镜和体外电生理技术研究移植后3、6和9 d的空肠黏膜，评估大鼠模型小肠移植排斥反应的结构和功能演变。Lewis X Brown Norway F1杂交小鼠移植到Lewis大鼠的空肠袢中，最早发现的结构异常发生在移植后3 d内，包括微血管局灶性内皮细胞损伤和隐窝上皮细胞局灶性损伤。这两种改变都与相邻的大淋巴样细胞浸润有关，并且在接下来的6天内都明显进展并变得相当弥漫性。相比之下，绒毛吸收细胞直到术后第9天才出现明显的结构改变。与宿主空肠相比，同种异体移植物空肠上皮表现出多种功能异常。经皮细胞耐药性在第6天和第9天逐渐下降（P均小于0.05），但基线经皮细胞自发电位差仅在第9天受到影响（P < 0.01）。通过测量粘膜葡萄糖的电反应来评估同种异体移植物空肠的刺激吸收，直到第9天才显著减少（P < 0.05）。相比之下，通过测量浆膜茶碱电反应评估的刺激分泌在第6天减少（P < 0.01）。这些数据表明，从结构和功能上判断，排斥反应中最早的上皮损伤发生在隐窝，并与微血管水平的内皮损伤平行。因此，排斥反应的主要目标很可能是内皮细胞和隐窝上皮细胞。相比之下，绒毛上皮的结构和功能损伤仅在排斥反应的较晚时间才可检测到，并且很可能是与微血管损伤引起的缺血或隐窝损伤引起的上皮再生能力下降有关的继发性过程。最后，我们表明，在该模型中，通过主要组织相容性复合体，空肠移植的有害结构和功能后遗症在环孢素治疗下显着改善。图片
We assessed the structural and functional evolution of small intestinal transplant rejection in a rat model by use of 1-micron section, electron microscopic, and in vitro electrophysiologic techniques to study jejunal mucosa 3, 6, and 9 d posttransplantation. The earliest structural abnormalities detected in jejunal loops transplanted from Lewis X Brown Norway F1 hybrids into Lewis rats occurred within 3 d posttransplantation and consisted of focal endothelial cell injury of the microvasculature and focal injury of crypt epithelial cells. Both alterations were associated with adjacent infiltration of large lymphoid cells, and both markedly progressed and became rather diffuse over the following 6 d. In contrast, villus absorptive cells were not markedly altered in structure until the 9th postoperative day. As compared with host jejuna, allograft jejunal epithelium demonstrated multiple functional abnormalities. Transepithelial resistance declined progressively by days 6 and 9 (both P less than 0.05), although baseline transepithelial spontaneous potential difference was only affected at day 9 (P less than 0.01). Stimulated absorption by allograft jejuna, as assessed by measuring electrical response to mucosal glucose, was not significantly diminished until day 9 (P less than 0.05). In contrast, stimulated secretion assessed by measurement of electrical response to serosal theophylline was diminished by day 6 (P less than .01). These data suggest that the earliest epithelial injury during rejection, as judged both structurally and functionally, occurs in the crypt and is paralleled by endothelial injury at the level of the microvasculature. Thus, the primary targets for rejection are most likely endothelial cells and crypt epithelial cells. In contrast, structural and functional impairment of villus epithelium is detectable only at substantially later times during rejection and are most likely secondary processes related to either ischemia produced by microvascular injury or decreased epithelial regenerative ability secondary to crypt injury. Last, we show that the detrimental structural and functional sequellae of jejunal transplantation across the major histocompatibility complex in this model is strikingly ameliorated with cyclosporine therapy.Images