Perioperative production of vein graft to which transfer anti-arteriosclerosis gene for CABG with gene gun

基因枪转抗动脉硬化基因冠状动脉搭桥术围手术期制作静脉移植物

• 批准号: 11671336
• 负责人: ABE Takehisa
• 金额: $ 1.02万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671336/
• 关键词: gene gun; Diabetes Mellitus; rat; gene transfer; Epstein-Barr virus; plasmid; heart functon

Gene guns have been used to transfer genes into various organs, but there has been no report of successful gene gun mediated gene transfer into the heart. In this study, we assessed the possibility of gene therapy using a gene gun and an episomal plasmid vector. Gene expression persisted for 6 weeks. The episomal vector apparently contributed to long-lasting expression. Infiltration of monocytes or leukocytes was very faint. The β-gal DNA was detected in bombarded hearts but not other organs. Gene gun mediated transfer of the episomal vector into beating heart may provide a simple, efficient, and useful strategy for gene therapy.In diabetes mellitus (DM) patients, the character of left ventricular (LV) function is reported as diastolic dysfunction, but their cardiac functions in terms of mechanoenergetics have not been studied yet. Purpose : We investigated left ventricular (LV) mechanoenergetics using the excised blood-perfused Otsuka Long-Evans Tokushima Fatty (OLETF) rats (model of … More type II DM model rat) whole heart preparation. Animals were 6 long-term * (L-I ; 40-46 weeks of age) OLETF rats (L-I group), 6 long-term II (L-II ; 62-66 weeks of age) OLETF rats (L-II group) and 5 control LETO rats (control group). We assessed LV mechano-energetics valuses and western blots for SERCA2 in each group. Mean ESPmax, mean slopes and VO_2 intercepts of VO_2-PVA relations did not show any differences among the three rat groups. Maximum pacing rate decreased to 240 beats/min in L-II group. Mean logistic time constants at 240-bpm pacing in L-II group were significantly (P<0.05) longer than the constants in control group (18.2 vs. 13.5 msec). Mean protein level of SERCA2 in L-II group was significantly lower than that in L-I group and control group. Conclusion : We conclude that the lusitropic function is impaired bv depressed expression of SERCA2 in prolonged hyperglycemia rats, although LV systolic function is well preserved and the Ca^<2+> handling is compensated by external Ca^<2+> extrusion. Less

基因枪已被用于将基因转移到各种器官中，但尚未有成功的基因枪介导的基因转移到心脏中的报道。在这项研究中，我们评估了基因治疗的可能性，使用基因枪和附加型质粒载体。基因表达持续6周。附加型载体显然有助于持久表达。单核细胞或白细胞浸润非常微弱。在被轰击的心脏中检测到β-gal DNA，但在其他器官中未检测到。基因枪介导的游离型载体在心脏跳动中的转移为基因治疗提供了一种简单、有效和有用的策略。糖尿病（DM）患者的左心室功能以舒张功能障碍为特征，但从机械能学角度研究其心脏功能尚未见报道。目的：我们使用离体血液灌注的大冢长-伊文思德岛脂肪（OLETF）大鼠（ ...更多信息 II型糖尿病模型大鼠）全心制备。动物为6只长期 *（L-I ; 40-46周龄）OLETF大鼠（L-I组）、6只长期II（L-II ; 62-66周龄）OLETF大鼠（L-II组）和5只对照LETO大鼠（对照组）。我们评估了各组的左心室机械能值和SERCA 2的蛋白质印迹。VO_2-PVA关系的平均ESPmax、平均斜率和VO_2截距在三组大鼠间无差异。L-II组最大起搏频率降至240次/min。L-II组在240次/分起搏时的平均逻辑时间常数明显（P<0.05）长于对照组的常数（18.2比13.5毫秒）。L-II组SERCA 2蛋白水平显著低于L-I组和对照组。结论：我们的结论是，在长期高血糖大鼠中，尽管左室收缩功能保持良好，并且Ca^2+处理通过外部Ca^2+排出得到补偿，但通过抑制SERCA 2的表达，左室收缩功能受损。少

项目成果

Nishizagi K, et al: "In vivo gene transfer into rat hearts with Epstein-Barr virus-based episomal vectors using a gene gun."Transplant Proc.. 32(7). 2413-2414 (2000)

Nishizagi K 等人：“使用基因枪，使用基于 Epstein-Barr 病毒的附加型载体将基因体内转移到大鼠心脏中。”《移植过程》32(7)。

Kashibe K, et al: "Assessment of cartilage viability in the cryopreserved tracheal allograft by measurement of Na_2^<35>SO_4 incorporation."Transpl.Proc.. 32(7). 1655-1656 (2000)

Kashibe K等人：“通过测量Na_2^35SO_4掺入来评估冷冻保存的气管同种异体移植物中的软骨活力。”Transpl.Proc..32(7)。

Tsuyoshi T,et al: "New index for oxygen cost of contractility from curved end-systolic pressure-volume relations in cross-circulated rat hearts"Japanese Journal of Physiology. 49. 513-520 (1999)

Tsuyoshi T 等人：“根据交叉循环大鼠心脏收缩末期压力-容积关系弯曲的收缩性氧消耗的新指数”日本生理学杂志。

Nishizaki K, Mazda O, Dohi Y, Satoh E, Kawata T, Mizuguchi K, Yonemasu K, Kitamura S, Taniguchi S.: "In vivo gene transfer into rat hearts with Epstein-Barr virus-based episomal vectors using a gene gun."Transplant Proc.. 32. 2413-2414 (2000)

Nishizaki K、Mazda O、Dohi Y、Satoh E、Kawata T、Mizuguchi K、Yonemasu K、Kitamura S、Taniguchi S.：“使用基因枪，使用基于 Epstein-Barr 病毒的附加型载体将体内基因转移到大鼠心脏中。

Nishizaki K, Mazda O, Dohi Y, Kawata T, Mizuguchi K, Kitamura S, Taniguchi S.: "In vivo gene gun-mediated transduction into rat heart with Epstein-Barr virus-based episomal vectors."Ann Thorac Surg.. 70. 1332-7 (2000)

Nishizaki K、Mazda O、Dohi Y、Kawata T、Mizuguchi K、Kitamura S、Taniguchi S.：“使用基于 Epstein-Barr 病毒的附加型载体体内基因枪介导的大鼠心脏转导。”Ann Thorac Surg.. 70