MACROENCAPSULATED ARTIFICIAL PANCREAS

首先，进行未纯化的胰岛移植（UIT）实验以评价当使用同种移植物模型将未纯化的胰岛移植到门静脉中时，各种抗凝剂即肝素、抗凝血酶III（ATIII）、甲磺酸加贝酯（FOY<encircledR>）对门静脉压力、受体存活率和移植物存活率的影响。雄性Wistar大鼠（200- 300 g）用作供体和受体。在开始注射细胞后15分钟，测量门静脉压力。接受者被分为四组。用100单位肝素（组1，n=6）、肝素和200单位/kg抗凝血酶III（ATIII）（组2，n=6）或肝素和10 mg/kg甲磺酸加贝酯（FOY<encircledR>）（组3，n=6）进行未纯化胰岛移植（UIT）。第4组（n=5）为对照组，门静脉注射肝素100 U，未达到长期血糖正常，ATIII组有1例受者血糖正常10 d。两组6例中的2例，6例中的1例，6例中的3例，以及每组5例中无一例因门静脉高压症随后小肠坏死而死亡。第3组移植后门静脉压力明显低于第1组和第2组，但仍高于对照组，需要进一步的实验以实现安全有效的胰岛移植。第二，以大鼠胰岛为材料，对聚砜膜生物人工胰腺的功能进行了体外研究。我们使用了Field等人新开发的梯度分离技术，其中白蛋白包被（35%BSA）的大鼠胰岛在葡聚糖中分离。胰岛产量为700-800个/胰腺。用含300 mg/dl葡萄糖的RPMI溶液培养人工胰腺，用静态培养法观察胰岛的活力。平均胰岛素分泌量为29 ng/ml。

First, unpurified islet transplantation(U IT) experiments were performed to evaluate the effects of various anticoagulants i.e. heparin, antithrombin III (ATIII), gabexate mesilate (FOY<encircledR>) on portal vein pressure, recipient survival, and graft survival when unpurified islets are transplanted into the portal vein using the isograft model. Male Wistar rats (200-300g) were used as donors and recipients. Fifteen minutes after the start of injection of cells, the portal vein pressure was measured. Recipients were divided into four groups. Unpurified islet transplantation (UIT) was performed with 100 units of heparin (group 1, n=6), heparin and 200 units/kg of antithrombin III (ATIII) (group 2, n=6), or heparin and 10 mg/kg of gabexate mesilate (FOY<encircledR>) (group 3, n=6). In group 4, 100 units of heparin was injected into the portal vein without transplantation as control (n=5).Long-term normoglycemia was not achieved, but one of the recipients in ATIII group was normoglycemic for 10 days. Two of 6, one of 6, three of 6, and none of 5 recipients in each group died due to portal hypertension followed by small bowel necrosis. In group 3, the portal pressure after transplantation was significantly lower than that in group 1 and 2, but still higher than that in controls.Further experiments are necessary to achieve safe and effective islet transplantation.Second, the function of bio-artificial pancreas derived from polysulfone membrane were investigated in vitro by using rat pancreatic islets. We used a gradient separation technique newly developed by Field et al , in which albumin-coated (35%BSA) rat islets are isolated in Dextran. The islets yield were 700-800 per pancreas. The viability of islets were investigated by static incubation which an artificial pancreas was incubated in RPMI solution containing 300 mg/dI of glucose. The mean insulin secretion was 29 ng/ml.