Czikk M J, Green L R, Kawagoe Y, McDonald T J, Hill D J, Richardson B S
CIHR Group in Fetal and Neonatal Health and Development, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
J Soc Gynecol Investig. 2001 Jul-Aug;8(4):191-7. doi: 10.1016/s1071-5576(01)00114-9.
To determine whether repetitive umbilical cord occlusion resulting in fetal hypoxemia but not cumulative acidosis also affects fetal glucose levels and the levels of the regulatory hormones insulin and glucagon, by altering glucose delivery and with repetitive insults by inducing fetal glucose production, thus possibly affecting pancreatic development.
Fifteen chronically catheterized fetal sheep were studied over 21 days. Umbilical cord occlusions (UCOs) (duration 90 seconds) were performed every 30 minutes for 3-4 hours each day. Fetal arterial blood was sampled at predetermined times on days 1, 9, and 18 for blood gases, pH, glucose, lactate, insulin, and glucagon. When animals were sacrificed, fetal pancreatic tissues were collected for insulin immunostaining.
Blood glucose decreased acutely with each UCO but showed a cumulative increase of approximately 30% over the course of each sampling day. Although plasma insulin levels also increased over the course of sampling on days 9 and 18, plasma glucagon levels remained unchanged throughout the study. The percentage of pancreatic islet cells immunopositive for insulin, which averaged 67%, was also unchanged in experimental compared with control animals.
Umbilical cord occlusion during the latter part of pregnancy, which caused severe but limited hypoxemia, also resulted in acute decreases in blood glucose levels because of reduced exogenous glucose delivery and a cumulative increase in glucose in response to repetitive insults, possibly by inducing fetal glucose production, enhancing glucose delivery, or both. However, repetitive UCO as studied had minimal effect on plasma insulin levels and no effect on glucagon levels or on pancreatic immunostaining for insulin, and thus had no evident effect on pancreatic development.
通过改变葡萄糖供应以及诱导胎儿葡萄糖生成的反复损伤，确定导致胎儿低氧血症但无累积酸中毒的反复脐带闭塞是否也会影响胎儿血糖水平以及调节激素胰岛素和胰高血糖素的水平，从而可能影响胰腺发育。
对15只长期插管的胎羊进行了为期21天的研究。每天每30分钟进行一次脐带闭塞（UCO）（持续时间90秒），每次持续3 - 4小时。在第1、9和18天的预定时间采集胎儿动脉血，检测血气、pH值、葡萄糖、乳酸、胰岛素和胰高血糖素。处死动物时，收集胎儿胰腺组织进行胰岛素免疫染色。
每次UCO后血糖均急性下降，但在每个采样日期间累计升高约30%。虽然在第9天和18天的采样过程中血浆胰岛素水平也有所升高，但在整个研究过程中血浆胰高血糖素水平保持不变。与对照动物相比，实验动物中胰岛素免疫阳性的胰岛细胞百分比平均为67%，也没有变化。
妊娠后期的脐带闭塞导致严重但有限的低氧血症，由于外源性葡萄糖供应减少，导致血糖水平急性下降，并且由于反复损伤，可能通过诱导胎儿葡萄糖生成、增强葡萄糖供应或两者兼而有之，血糖出现累积升高。然而，所研究的反复UCO对血浆胰岛素水平影响极小，对胰高血糖素水平或胰岛素胰腺免疫染色无影响，因此对胰腺发育无明显影响。
