Jaworski M A, Jewell L D, Honore L, Mehta J G, Bayens-Simmonds J, McGuire-Clark P, Schouls J J, Yap W Y
Department of Pediatrics, University of Alberta, Edmonton.
Clin Invest Med. 1987 Sep;10(5):488-95.
We have developed a protocol of prophylactic cyclosporin A administration which confers complete and permanent protection against insulin-dependent diabetes mellitus in diabetes-prone BioBreeding rats. Spontaneous insulin-dependent diabetes mellitus developed in about 50% of BioBreeding rats, between 10 and 18 weeks of age. Prophylactic cyclosporin A (10 mg/kg/day p.o.), started at 6 weeks of age and terminated at 21 weeks of age, completely prevented insulin-dependent diabetes mellitus: 0% (0/25) cyclosporin A-treated compared to 46% (11/24) control rats developed insulin-dependent diabetes mellitus (p less than 0.001). Protection against insulin-dependent diabetes mellitus was lifelong, provided cyclosporin A prophylaxis was initiated when insulitis was minimal or absent, and pancreatic insulin content was normal. Cyclosporin A prophylaxis initiated later, but still before the onset of clinical symptoms (8-9 weeks), and terminated at 22-23 weeks, was only partially effective; 5/20 (25%) of cyclosporin A-treated rats developed insulin-dependent diabetes mellitus, compared to 60% (12/20) of controls (p less than 0.05). Cyclosporin A prophylaxis started at the appropriate time (6 weeks) but terminated prematurely (17-19 weeks of age) was not effective; insulin-dependent diabetes mellitus developed in 20% (3/15), compared to 50% (7/14) controls (p greater than 0.05); insulin-dependent diabetes mellitus developed after cessation of therapy. We conclude that effective and permanent moderate-dose cyclosporin A prophylaxis of insulin-dependent diabetes mellitus in BioBreeding rats requires (1) early initiation of treatment, when islet morphology and hormone content are still normal; and (2) prolonged treatment, with continuation of prophylaxis past the end of the at-risk period.(ABSTRACT TRUNCATED AT 250 WORDS)
我们已经制定了一项预防性给予环孢素A的方案，该方案能使易患糖尿病的BioBreeding大鼠完全且永久地免受胰岛素依赖型糖尿病的侵害。约50%的BioBreeding大鼠在10至18周龄时会自发患上胰岛素依赖型糖尿病。预防性给予环孢素A（口服，10毫克/千克/天），从6周龄开始，至21周龄结束，可完全预防胰岛素依赖型糖尿病：环孢素A治疗组的发病率为0%（0/25），而对照组为46%（11/24），两组相比差异有统计学意义（p<0.001）。只要在胰岛炎轻微或不存在且胰腺胰岛素含量正常时开始给予环孢素A进行预防，对胰岛素依赖型糖尿病的保护就是终身的。如果在临床症状出现前较晚的时候（8 - 9周）开始给予环孢素A预防，并在22 - 23周结束，效果则只是部分有效；环孢素A治疗组有5/20（25%）的大鼠患上胰岛素依赖型糖尿病，而对照组为60%（12/20），两组相比差异有统计学意义（p<0.05）。在合适的时间（6周）开始但过早终止（17 - 19周龄）环孢素A预防是无效的；治疗组有20%（3/15）的大鼠患上胰岛素依赖型糖尿病，对照组为50%（7/14），两组相比差异无统计学意义（p>0.05）；胰岛素依赖型糖尿病在治疗停止后出现。我们得出结论，在BioBreeding大鼠中，要有效且永久地通过中等剂量环孢素A预防胰岛素依赖型糖尿病，需要：（1）在胰岛形态和激素含量仍正常时尽早开始治疗；（2）延长治疗时间，在危险期结束后仍继续预防。（摘要截选至250字）
