胰腺移植及胰岛移植的现状

本文简要综述了胰腺移植与胰岛移植治疗1型及2型糖尿病的现状。     

胰岛移植早期血糖控制对大鼠胰岛移植效果的影响

目的　探讨胰岛移植早期血糖控制对大鼠胰岛移植效果的影响。方法　体外实验 :将新鲜制备的SD大鼠胰岛在 4种不同糖浓度中培养 5d后恢复至常规糖浓度中培养 3d ,观察其形态、存活时间及功能变化。胰岛移植实验 :将糖尿病SD大鼠随机分为 3组 :移植及胰岛素控血糖组 ;单纯移植组和未移植 (对照 )组。监测各组的血糖水平。结果　在体外 ,短期的高糖培养对SD大鼠胰岛的形态、存活时间无明显影响 ,但可降低其对高糖刺激的反应能力。在糖浓度恢复正常后 ,该功能可恢复。移植实验中 ,血糖控制组在移植后 14d时 ,受体鼠血糖 ( 2 7.0± 4.0 )mmol/L与对照组 ( 3 3 .1± 1.8)mmol/L间差异有显著性 (P <0 .0 5 ) ,而单纯移植组与对照组的血糖差异仅维持到移植后 8d。结论　移植早期的血糖控制有改善胰岛移植效果的作用。     

胰岛移植与微循环的相关性研究

目的　研究胰岛移植术后微循环的建立。方法　采用文献回顾的方法对胰岛移植与微循环的相关性研究加以综述。结果　移植后的胰岛再血管化在 1周内开始出现 ,并于 10～ 14天内完成 ,其微脉管系统的结构与胰腺的原位胰岛较相似 ,其血流灌注方向从 β细胞→α细胞→δ细胞 ,并来源于宿主的微血管床。移植后胰岛的间质压力明显低于毛细血管压。同基因与异基因胰岛移植术后微循环建立是不同的 ,异基因移植可出现微循环衰竭现象。影响微循环建立的因素有 :①胰岛分离后的培养温度 ;②胰岛培养天数及冻存方法 ;③免疫抑制剂 ;④血糖 ;⑤促血管生存因子。结论　移植后胰岛有足够的微血管血供对其移植的成功及其功能的维持起着重要的作用 ,通过研究有助于了解移植胰岛存活的机理。     

小鼠胰岛的分离及胰岛移植

目的研究小鼠胰岛分离和移植的方法。方法在Gotoh等所介绍的小鼠胰岛分离方法的基础上作了一些改进,由原来经胆总管注入胶原酶消化液改为由胆囊注入,并在消化液和Ficoll分离液中加入了胰酶抑制剂和BSA。结果使分离纯化后的胰岛产量由原来方法的41.7±13.2个提高到了266.5±32.1个(P<0.01),活性在95%以上,除了少量导管外几乎不含腺泡组织。结论改进后的方法可以在肉眼条件下注入消化液,而不需要解剖显微镜,既方便了操作又提高了成功率;避免了整个消化和分离过程中胰酶对胰岛的消化作用,提高了得率,且具有很好的重复性。     

经门静脉胰岛移植后移植物的早期丢失

经门静脉胰岛移植是目前治疗Ⅰ型糖尿病最有效的治疗方法.然而有高达70%的胰岛移植物在移植后2周内被破坏,只有少部分植入的胰岛在肝脏内定植后发挥作用,这导致了胰岛移植效果的不佳.本文对引起这一早期胰岛移植物丢失的原因及其应对措施予以综述.     

胰腺移植及胰岛移植的现状

本文简要综述了胰腺移植与胰岛移植治疗1型及2型糖尿病的现状。     

胰岛肝脏移植的研究及现状

胰岛移植是治疗糖尿病的有效手段,其临床应用具有广阔的前景。肝脏具有特殊的解剖和生理特点是胰岛移植的理想部位。     

胃黏膜下层胰岛移植物的生存率与功能的实验研究

目的 探讨胃黏膜下层胰岛移植的可行性.方法 应用雄性Wistar-Furth大鼠,STZ介导糖尿病大鼠模型.同种同基因大鼠体外胰岛分离纯化,分别移植进入糖尿病大鼠胃黏膜下层或肾被膜下,移植后不同时间段评估移植物生存率与代谢功能.结果 移植后早期移植胰岛被有效确认,并迅速分泌胰岛素逆转大鼠高血糖状况,糖耐受功能良好,与肾被膜下移植组比较,差异无显著意义.移植后4周,胃黏膜下移植组胰岛移植物胰岛素分泌功能逐渐丧失.结论 胃黏膜下胰岛移植技术具有良好的开发前景,如何提高其远期效果有待进一步考证.     

Topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway

Impaired wound healing is one of a variety of severe diabetic complications and involves many factors, including consistent oxidative stress, prolonged inflammation, impaired angiogenesis, and delayed re-epithelialization. Despite the severe negative impacts that impaired wound healing has on patients’ lives, detailed mechanisms and effective therapies are still not fully developed. In this study, we aim to investigate the potential effects and mechanisms of topical administration of pterostilbene and resveratrol on burn wound healing in diabetes. Our in vitro experiments in human umbilical vein endothelial cells showed that long term exposure of hyperglycemia induces oxidative stress and suppression of hypoxia inducible factor1α (HIF1α) signaling pathway, and pterostilbene treatment completely, while resveratrol treatment partly, reversed this effect. Further in vivo experiments in diabetic rats showed that topical administration of pterostilbene exhibited stronger efficacy than resveratrol in normalizing oxidative stress, HIF1α activity, and accelerating burn wound healing in diabetes. We conclude that topical administration of pterostilbene accelerates burn wound healing in diabetes through activation of the HIF1α signaling pathway; thus, pterostilbene may be a potential candidate for clinical treatment of burn wound healing in diabetes.     

CTLA4-Ig-modified dendritic cells inhibit lymphocyte-mediated alloimmune responses and prolong the islet graft survival in mice

The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In this study, we transfected CTLA4-Ig gene into dendritic cells (DCs), and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on pancreatic islet allograft in mice. An IDDM C57BL/6 murine model induced by streptozotocin is as model mouse. The model mice were transplanted of the islet cells isolated from the BALB/c mice to their kidney capsules, and injected of CTLA4-Ig modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation and induce its apoptosis; whereas, unmodified DCs (umDCs) promoted the murine lymphocyte proliferation. Compared with injection of umDCs and IgG1 modified DCs, the injection of mDCs prolonged IDDM mice's allograft survival, and normalized their plasma glucose (PG) levels within 3 days and maintained over 2 weeks. The level of IFN-gamma was lower and the level of IL-4 was higher in mDCs treated recipient mice than that in control mice, it indicated that mDCs led to Th1/Th2 deviation. After 7 days of islet transplantation, HE stain of the renal specimens showed that the islets and kidneys were intact in structure, and islet cells numbers are increased in mDCs treated mice. Our studies suggest that DCs expressing CTLA4-Ig fusion protein can induce the immune tolerance to islet graft and prolong the allograft survival through the inhibition of T cell proliferation in allogeneic mice.     

Quality control for clinical islet transplantation: organ procurement and preservation, the islet processing facility, isolation, and potency tests

Pancreatic islet transplantation has become one of the ideal treatments for patients with type 1 diabetes mellitus due to improvements in isolation techniques and immunosuppression regimens. In order to ensure the safety and rights of patients, isolated islets need to meet the criteria for regulation as both a biological product and a drug product. For the constant success of transplantation, therefore, all investigators involved in clinical islet transplantation must strive to ensure the safety, purity, and potency of islets in all the phases of clinical islet isolation and transplantation. In this review, we summarize the quality control for clinical islet isolation and transplantation, and the latest topics of pre-transplant islet assessment.     

无功能胰岛细胞瘤26例诊治分析并文献综述

目的 探讨无功能胰岛细胞瘤(NICT)临床病理特点及诊治方法.方法 对本院收治的NICT患者临床病理资料进行回顾性分析并做文献综述.结果 共统计26例NICT患者的临床病理资料,文献综述获得有效文献37篇,共报道NICT 569例.我国NICT好发于女性,男女比例约3∶7,发病平均年龄35岁,绝大部分为单发病例,胰腺头颈部及体尾部发生比例相仿,恶性居多,外科治疗远期效果好.结论 NICT症状缺乏特异性,超声和CT可作为首选的检查方法.外科手术是治疗该病、延长患者生存时间的有效手段.     

Effect of metallothionein on the renal injury induced by chronic intermittent hypoxia in mice

Objective To investigate the mechanism of chronic intermittent hypoxia (CIH)- induced renal injury and the protection of metallothionein (MT). Methods 8-10 weeks old male MT-1 transgenic (MT-TG) mice (n=12) and the wide type (WT) mice (n=12) were randomly divided into two groups respectively, Air mimic control(Ctrl) group (n=6) and CIH group (n=6). The period of chronic intermittent hypoxia was continued for 8 weeks. The CIH paradigm consisted of 20.9% O2 and 8% O2 fraction of inspiration O2 (FiO2) alternation cycles (30 episodes per hour) with 20 seconds at the nadir FiO2 for 12 hours/day during daylight. The nadir hemoglobin oxygen saturations mainly ranged from 60% to 70%. Urine, blood, kidney were collected at the end of study respectively. Histopathology, Western blotting and colorimetric method for related target were performed respectively. Results In WT mice, renal fibrosis, the expression of connective tissue growth factor (CTGF), type-1 plasminogen activator inhibitor (PAI - 1), hypoxia - inducible factor 1α (HIF - 1α), transforming growth factor β1 (TGF-β1), phosphorylated Smad2 and the MDA content were significantly increased by CIH (P＜0.01). In WT mice, the expression of MT detected by using Western blotting was significantly decreased by CIH (P＜0.01). However, in MT-TG mice, above-mentioned indicators showed no significant difference between CIH and Ctrl group. Conclusions Oxidative stresses is the main mechanism of CIH - induced renal injury. The possible molecular mechanism of CIH - induced renal injury is that CIH increases the expression of HIF - 1α in kidney tissue, then activate the TGF - β1 - Smad2 signaling pathway and lead to the renal fibrosis. The protection of MT on CIH-induced renal injury may be via its antioxidant effect.