Juranek Judyta K, Aleshin Alexey, Rattigan Eileen M, Johnson Lynne, Qu Wu, Song Fei, Ananthakrishnan Radha, Quadri Nosirudeen, Yan Shi Du, Ramasamy Ravichandran, Schmidt Ann Marie, Geddis Matthew S
Division of Surgical Science, Columbia University Medical Center, New York, NY, 10032, USA.
Biochem Insights. 2010 Sep 1;2010(3):47-59. doi: 10.4137/BCI.S5340.
The aim of our project was to study the effect of streptozotocin (STZ)-induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products), and its ligands-S100B and Carboxymethyl Lysine (CML)-advanced glycation endproduct (AGE) in the laboratory pig. Six months after STZ-injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products-methyl-glyoxal (MG) were performed. The results of our study revealed that STZ-injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT) and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.
我们项目的目的是研究链脲佐菌素（STZ）诱导的高血糖对实验猪坐骨神经形态、血浆标志物以及晚期糖基化终产物受体（RAGE）及其配体——S100B和羧甲基赖氨酸（CML）（一种晚期糖基化终产物）免疫组化表达的影响。在注射STZ六个月后，进行了血浆测量、坐骨神经纤维密度的形态计量分析、潜在分子神经病变相关因素的免疫荧光分布检测、血浆晚期糖基化终产物水平的酶联免疫吸附测定（ELISA）以及坐骨神经中一种糖基化前体和糖酵解中间产物——甲基乙二醛（MG）水平的高效液相色谱分析。我们的研究结果显示，注射STZ的动物血浆葡萄糖、γ-谷氨酰转移酶（GGT）和甘油三酯水平升高。与对照动物相比，注射STZ的猪的坐骨神经中小直径有髓纤维数量显著减少，RAGE和S100B的免疫反应性更高，MG水平升高。我们的结果与高血糖/糖尿病诱发的周围神经病变患者的临床发现相符，表明家猪可能是研究高血糖诱导的周围神经神经并发症潜在机制的合适大型动物模型，并且可作为神经病变候选药物临床前评估的相关模型。
