Adenovirus-mediated anti-apoptotic gene (bcl-2) transfer in the transplant pancreas

腺病毒介导的抗凋亡基因（bcl-2）在移植胰腺中的转移

• 批准号: 10671158
• 负责人: MAKUUCHI Masatoshi
• 金额: $ 2.11万
• 依托单位: Tokyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671158/
• 关键词: pancreas; transplantation; insulin; adenovirus; Bcl2 (anti-apoptotic gene); アデノウィルス; Bcl_2; 拒絶反応; 膵臓移植

Background. Hyperinsulinemia, which is usually related to insulin resistance, is considered to be an important risk factor for coronary artery disease. The present study examines the influence of portal delivery of endogenous insulin after pancreas transplantation on plasma lipid metabolism, as compared to systemic delivery of insulin.Method. Pancreas was transplanted heterotopically in normal rats by anastomosis of the donor portal vein to the recipient portal vein (PPTx) or inferior vena cava (CPTx) as an in vivo model of endogenous hyperinsulinemia.Results. The mean value of plasma insulin concentration of CPTx and PPTx rats was 149% and 165% that of control rats, whereas the plasma glucose concentration of CPTx and PPTx rats did not differ significantly from that of control rats. Plasma triglyceride (TG) concentrations were significantly lower in both PPTx and CPTx rats than control rats. During the intravenous glucose tolerance test, the area under the insulin concentration curves (AUC) of CPTx and PPTx rats was 204% and 215% that of control rats, and they were correlated negatively with plasma TG concentrations. Plasma cholesterol and TG concentrations were significantly lower in PPTx rats than in control and CPTx rats.Conclusions. Chronic hyperinsulinemia has a dose-dependent inhibitory effect on the regulation of plasma TG concentrations in rats with a transplanted pancreas. Significant lower lipid levels in PPTx rats than in CPTx rats suggest that portal delivery of insulin from the transplanted pancreas is relatively preventive for the atherosclerotic process as compared to systemic delivery of insulin.

背景。高胰岛素血症通常与胰岛素抵抗有关，被认为是冠状动脉疾病的重要危险因素。本研究探讨了与全身胰岛素输送相比，胰腺移植后门静脉输送内源性胰岛素对血浆脂质代谢的影响。通过将供体门静脉与受体门静脉（PPTx）或下腔静脉（CPTx）吻合，将胰腺异位移植到正常大鼠体内，作为内源性高胰岛素血症的体内模型。结果。 CPTx和PPTx大鼠的血浆胰岛素浓度平均值分别为对照大鼠的149%和165%，而CPTx和PPTx大鼠的血浆葡萄糖浓度与对照大鼠没有显着差异。 PPTx 和 CPTx 大鼠的血浆甘油三酯 (TG) 浓度显着低于对照大鼠。静脉糖耐量试验时，CPTx和PPTx大鼠的胰岛素浓度曲线下面积（AUC）分别为对照大鼠的204%和215%，且与血浆TG浓度呈负相关。 PPTx 大鼠的血浆胆固醇和 TG 浓度显着低于对照和 CPTx 大鼠。结论。慢性高胰岛素血症对胰腺移植大鼠血浆TG浓度的调节具有剂量依赖性抑制作用。 PPTx 大鼠的脂质水平显着低于 CPTx 大鼠，表明与全身输送胰岛素相比，从移植胰腺门静脉输送胰岛素对于动脉粥样硬化过程具有相对预防作用。

项目成果

原田 賢治: "マクロファージのアポトーシスと動脈硬化"内分泌・糖尿病科. 9. 46-53 (1999)

Kenji Harada：“巨噬细胞凋亡和动脉硬化”，内分泌和糖尿病系，9. 46-53 (1999)。

Hideki Abe, et al.: "Chronic inhibitory effect of insulin in rats with transplanted pancreas."Transplantation. (in press). (2000)

Hideki Abe 等人：“胰岛素对胰腺移植大鼠的慢性抑制作用。”移植。

Hideaki Abe, et al.: "Chronic inhibitory effect of insulin in rats with transplantation pancreas"Transplantation. (in press).

Hideaki Abe 等人：“胰岛素对移植胰腺大鼠的慢性抑制作用” 移植。

原田賢治: "マクロファージのアポトーシスと動脈硬化"内分泌・糖尿病科. 9(1). 46-53 (1999)

Kenji Harada：“巨噬细胞凋亡和动脉硬化”，内分泌和糖尿病系 9(1)。

Harada K, Ishibashi S, Yamada N.: "Association of tyrosine-phosphorylated 39 kD and 29 kD proteins with apoptotic cell death induced by monocyte/macrophage colony stimulating factor deprivation."American heart association 71ィイD1stィエD1 Scientific Sessions.

Harada K、Ishibashi S、Yamada N.：“酪氨酸磷酸化 39 kD 和 29 kD 蛋白质与单核细胞/巨噬细胞集落刺激因子剥夺诱导的细胞凋亡的关联。”美国心脏协会 71D1StierD1 科学会议。