Orloff M J, Greenleaf G, Girard B
Department of Surgery, School of Medicine, University of California, San Diego.
Surgery. 1990 Aug;108(2):179-89; discussion 189-90.
To answer the crucial question regarding reversibility of diabetic somatic neuropathy by whole-pancreas transplantation, metabolic studies and electron microscopic morphometry of the sciatic and testicular nerves were performed monthly for 2 years in three groups of highly inbred rats: (1) NC, 47 nondiabetic controls; (2) DC, 90 untreated alloxan-induced diabetic controls; and (3) DT, 230 diabetic rats given syngeneic pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of diabetes mellitus (DM). Six diabetic nerve lesions were quantitated by a "blind" protocol: (1) loss of myelinated axons, (2) intraaxonal glycogen deposits, (3) axons with glycogen deposits, (4) demyelinated axons, (5) degenerating axons, and (6) loss of intact axoglial junctions in paranodal terminal myelin loops. In the DT group, testicular nerve specimens were obtained just before transplantation and at death so that each animal served as its own control. As we have observed previously in untreated diabetic controls, all six nerve lesions progressed relentlessly for 2 years, in contrast to nondiabetic controls (p less than 0.01). Whole-pancreas transplants produced complete metabolic control of DM for life and reversed all six lesions in both sciatic and testicular nerves, even when done late in the course of DM. There was complete reversal of the nerve lesions when pancreatic transplantation was done within 15 months of the onset of DM. These results provide the first demonstration of reversal of diabetic somatic neuropathy by any form of DM therapy and extend our previous work in which whole-pancreas transplants were found to prevent both diabetic neuropathy and nephropathy and reverse mesangial enlargement in the kidney.
为了回答全胰腺移植能否逆转糖尿病性躯体神经病变这一关键问题，对三组高度近交系大鼠进行了为期2年的每月一次的代谢研究以及坐骨神经和睾丸神经的电子显微镜形态测定：（1）NC组，47只非糖尿病对照大鼠；（2）DC组，90只未治疗的四氧嘧啶诱导的糖尿病对照大鼠；（3）DT组，230只糖尿病大鼠，在糖尿病（DM）诱导后6个月至21个月接受了同基因胰十二指肠移植。通过一种“盲法”方案对六种糖尿病神经病变进行定量：（1）有髓轴突丧失；（2）轴突内糖原沉积；（3）有糖原沉积的轴突；（4）脱髓鞘轴突；（5）变性轴突；（6）结旁终末髓鞘环中完整轴突-神经胶质连接丧失。在DT组中，在移植前和处死时获取睾丸神经标本，以便每只动物作为自身对照。正如我们之前在未治疗的糖尿病对照中观察到的，与非糖尿病对照相比（p<0.01），所有六种神经病变在2年中持续进展。全胰腺移植使DM获得终身完全代谢控制，并逆转了坐骨神经和睾丸神经中的所有六种病变，即使在DM病程晚期进行移植也是如此。在DM发病后15个月内进行胰腺移植时，神经病变完全逆转。这些结果首次证明了任何形式的DM治疗均可逆转糖尿病性躯体神经病变，并扩展了我们之前的研究工作，即发现全胰腺移植可预防糖尿病神经病变和肾病，并逆转肾脏系膜增大。
