Henninger Nadja, Woderer Stefanie, Kloetzer Hans-Martin, Staib Arnulf, Gillen Ralph, Li Li, Yu Xiaolei, Gretz Norbert, Kraenzlin Bettina, Pill Johannes
Medical Research Center, University Hospital Mannheim, University of Heidelberg, D68167 Mannheim, Germany.
Biosens Bioelectron. 2007 Aug 30;23(1):26-34. doi: 10.1016/j.bios.2007.03.016. Epub 2007 Mar 30.
Considerable progress in improved control of disturbed glucose metabolism can be expected by continuous glucose monitoring. The aim of the study was to evaluate in male Sprague-Dawley rats tissue response to implantation of a new amperometric glucose-oxidase-based glucose sensor (NTS) compared to a commercially available sensor system CGMS of MiniMed. Both sensors were tested under working conditions over a period of 3 days. Using NTS, glucose in interstitial fluid reflected glucose in arterial blood even in rapidly changing hyper- and hypoglycaemia whereas the CGMS did not detect the experimentally induced glucose changes adequately. Gene expression profiling was performed using Affymetrix chips. Acute phase response to injury by sensor application for a short time is indicated by down regulation of the increase in mRNA of proteases e.g. metallothionein-1alpha and matrix metalloprotease-3 at day 3. Improvement of anabolic situation is suggested by decrease in mRNA of insulin-like growth factor binding protein whereas increase of heme oxygenase and hypoxia-inducible factor may be related to defense mechanisms. Changes of mRNA together with slight fibrous capsule formation suggest good histocompatibility. Comparability of the patterns of changed mRNA in tissue surrounding SCGM with and without operating voltage as shown in dendrogram indicates no contribution of hydrogen peroxide to worsening biocompatibility. Beside established histological investigations of foreign body reaction weeks or months after implantation, gene expression profiling provides additional information to biocompatibility already early after implantation.
通过持续葡萄糖监测，有望在改善血糖代谢紊乱的控制方面取得显著进展。本研究的目的是评估雄性Sprague-Dawley大鼠对一种新型基于葡萄糖氧化酶的安培型葡萄糖传感器（NTS）植入的组织反应，并与美敦力公司市售的传感器系统CGMS进行比较。两种传感器均在工作条件下进行了为期3天的测试。使用NTS时，即使在快速变化的高血糖和低血糖情况下，组织间液中的葡萄糖也能反映动脉血中的葡萄糖，而CGMS却不能充分检测到实验诱导的葡萄糖变化。使用Affymetrix芯片进行基因表达谱分析。在第3天，蛋白酶如金属硫蛋白-1α和基质金属蛋白酶-3的mRNA增加受到下调，这表明传感器短时间应用对损伤的急性期反应。胰岛素样生长因子结合蛋白的mRNA减少提示合成代谢状态改善，而血红素加氧酶和缺氧诱导因子的增加可能与防御机制有关。mRNA的变化以及轻微的纤维囊形成提示良好的组织相容性。树状图显示，有和无工作电压时，SCGM周围组织中mRNA变化模式具有可比性，这表明过氧化氢对生物相容性恶化没有影响。除了在植入后数周或数月对外来异物反应进行既定的组织学研究外，基因表达谱分析在植入后早期就能为生物相容性提供额外信息。
