MACROENCAPSULATED ARTIFICIAL PANCREAS

首先，采用非纯化胰岛移植（U IT）实验，评估不同抗凝剂(肝素、抗凝血酶III （ATIII）、甲酸加贝酸酯（FOY<encircledR>）对门静脉压力、受体存活和移植物存活的影响。雄性Wistar大鼠（200-300g）作为供体和受体。细胞注射开始15分钟后，测量门静脉压力。接受者被分为四组。未纯化胰岛移植（UIT）采用100单位肝素（第1组，n=6）、200单位/kg抗凝血酶III（第2组，n=6）或10 mg/kg甲磺酸加贝酸酯（FOY<encircledR>）（第3组，n=6）。第4组在门静脉内注射肝素100单位，不作移植，作为对照（n=5）。长期血糖未达到正常水平，但ATIII组有1例患者血糖维持10天正常。每组6例受者中2例，1例，3例，5例无一例因门静脉高压症并发小肠坏死死亡。3组移植后门静脉压力明显低于1、2组，但仍高于对照组。要实现安全有效的胰岛移植，还需要进一步的实验。其次，以大鼠胰岛为材料，研究聚砜膜制备的生物人工胰腺的体外功能。我们采用Field等人新开发的梯度分离技术，用右旋糖酐分离白蛋白包被（35%BSA）的大鼠胰岛。每个胰腺的胰岛产量为700-800个。将人工胰腺置于含300 mg/dI葡萄糖的RPMI溶液中静孵育，观察胰岛细胞活力。胰岛素平均分泌量为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.