Gores P F, Boudreaux J P, Hesse U J, Najarian J S, Sutherland D E
Surgery. 1987 May;101(5):557-61.
Cyclosporine administration prolongs the survival of immediately vascularized allografts. However, its role in the prevention of rejection of dispersed pancreatic islet allografts is uncertain, and some studies have suggested that it may be harmful. We performed total pancreatectomies in 21 mongrel dogs, followed by intrasplenic autotransplantation of islet-enriched, dispersed pancreatic tissue prepared by means of ductal perfusion and collagenase digestion. Ten dogs received no other therapy (controls) and 11 received orally administered cyclosporine from the day before to 30 days after transplantation. Therapeutic blood levels of cyclosporine were documented by means of high-pressure liquid chromatography. There was no difference in engraftment in six of 10 controls, and eight of 11 cyclosporine-treated dogs remained normoglycemic for more than 30 days. Intravenous glucose tolerance test results (K values), fasting serum insulin levels, and insulin secretion in response to a glucose challenge were similar in the two groups. There were two late treatment failures in the control group and one in the cyclosporine-treated group. We were unable to detect an adverse effect of cyclosporine on the engraftment or function of canine islet autografts. We conclude that cyclosporine remains a promising drug for use in studies of islet transplantation in human beings.
给予环孢素可延长即刻血管化同种异体移植物的存活时间。然而,其在预防分散的胰岛同种异体移植排斥反应中的作用尚不确定,一些研究表明它可能有害。我们对21只杂种犬进行了全胰切除术,随后将通过导管灌注和胶原酶消化制备的富含胰岛的分散胰腺组织自体移植到脾脏内。10只犬未接受其他治疗(对照组),11只犬在移植前一天至移植后30天口服环孢素。通过高压液相色谱法记录环孢素的治疗血药浓度。10只对照组中有6只的移植情况无差异,11只接受环孢素治疗的犬中有8只在30多天内血糖保持正常。两组的静脉葡萄糖耐量试验结果(K值)、空腹血清胰岛素水平以及对葡萄糖刺激的胰岛素分泌相似。对照组有2例晚期治疗失败,环孢素治疗组有1例。我们未能检测到环孢素对犬胰岛自体移植的植入或功能有不良影响。我们得出结论,环孢素在人类胰岛移植研究中仍是一种有前景的药物。