Hughes Stephen J, Davies Susan E, Powis Stephen H, Press Martin
Department of Endocrinology, Royal Free Campus, Royal Free and University College Medical School, London, United Kingdom.
Transplantation. 2003 Jun 27;75(12):1954-9. doi: 10.1097/01.TP.0000066805.39716.23.
Hypoxia in the portal vein may compromise the survival of intraportally transplanted pancreatic islets. We therefore examined the effect of inspired oxygen on the outcome of islet transplantation.
Blood glucose concentrations, glucose tolerance, and the size and number of surviving islets were measured in diabetic rats housed for 48 hr under hyperoxic (100% O(2)), hypoxic (11% O(2)), or normoxic (21%O(2)) conditions after intraportal transplantation of 350, 500, 700, or 1,000 syngeneic islets.
In normoxic diabetic rats, the smallest graft size to consistently restore normoglycemia was 1,000 islets. A graft size of 700 islets was effective in only three of nine animals, whereas 500 islets were ineffective in all eight animals undergoing transplantation. In contrast, in hyperoxically housed rats, graft sizes of 700 or 500 islets restored normoglycemia in eight of nine or five of eight animals, respectively. In those animals that became normoglycemic, the glucose tolerance of the hyperoxically treated rats receiving 700 islets was almost identical to that of normoxically housed animals receiving 1,000 islets. The average size of the islets 6 weeks after transplantation was the same in livers of hyperoxic and control rats. However, the total islet area and number of islets engrafted in hyperoxic rats was significantly increased when compared with livers from normoxic animals receiving the same graft size, so the area in hyperoxic rats receiving 700 islets was not significantly different from normoxic recipients of 1,000 islets.
Hyperoxia posttransplantation increases the number of islets that survive the engraftment process and allows normalization of plasma glucose levels with a smaller number of transplanted islets.
门静脉缺氧可能会损害经门静脉移植的胰岛的存活。因此,我们研究了吸入氧气对胰岛移植结果的影响。
将350、500、700或1000个同基因胰岛经门静脉移植到糖尿病大鼠体内,分别置于高氧(100% O₂)、低氧(11% O₂)或常氧(21% O₂)环境中饲养48小时后,测量其血糖浓度、葡萄糖耐量以及存活胰岛的大小和数量。
在常氧环境下的糖尿病大鼠中,持续恢复正常血糖所需的最小移植胰岛量为1000个。700个胰岛的移植量仅在9只动物中的3只有效,而500个胰岛的移植量在所有8只接受移植的动物中均无效。相比之下,在高氧环境下饲养的大鼠中,700个或500个胰岛的移植量分别使9只动物中的8只或8只动物中的5只恢复了正常血糖。在那些血糖恢复正常的动物中,接受700个胰岛移植的高氧处理大鼠的葡萄糖耐量与接受1000个胰岛移植的常氧环境大鼠几乎相同。移植6周后,高氧环境大鼠和对照大鼠肝脏中胰岛的平均大小相同。然而,与接受相同移植量的常氧环境动物的肝脏相比,高氧环境大鼠中植入的胰岛总面积和数量显著增加,因此接受700个胰岛移植的高氧环境大鼠的面积与接受1000个胰岛移植的常氧环境大鼠无显著差异。
移植后高氧环境可增加移植过程中存活的胰岛数量,并使较少数量的移植胰岛实现血糖水平正常化。