健康和2型糖尿病Goto-Kakizaki大鼠坐骨神经损伤与修复后神经再生的性别差异
Gender differences in nerve regeneration after sciatic nerve injury and repair in healthy and in type 2 diabetic Goto-Kakizaki rats.
作者信息
Stenberg Lena, Dahlin Lars B
机构信息
Department of Clinical Sciences - Hand Surgery, Lund University, Skane University Hospital, Malmö, Sweden.
出版信息
BMC Neurosci. 2014 Sep 13;15:107. doi: 10.1186/1471-2202-15-107.
BACKGROUND
In view of the global increase in diabetes, and the fact that recent findings indicate that diabetic neuropathy is more frequently seen in males, it is crucial to evaluate any gender differences in nerve regeneration in diabetes. Our aim was to evaluate in short-term experiments gender dissimilarities in axonal outgrowth in healthy and in genetically developed type 2 diabetic Goto-Kakizaki (GK) rats, and also to investigate the connection between activated (i.e. ATF-3, Activating Transcription Factor 3) and apoptotic (cleaved caspase 3) Schwann cells after sciatic nerve injury and repair. Female and male diabetic GK rats, spontaneously developing type 2 diabetes, were compared with corresponding healthy Wistar rats. The sciatic nerve was transected and instantly repaired. After six days the nerve was harvested to measure axonal outgrowth (i.e. neurofilament staining), and to quantify the number of ATF-3 (i.e. activated) and cleaved caspase 3 (i.e. apoptotic) stained Schwann cells using immunohistochemistry.
RESULTS
Axonal outgrowth was generally longer in male than in female rats and also longer in healthy than in diabetic rats. Differences were observed in the number of activated Schwann cells both in the distal nerve segment and close to the lesion site. In particular the female diabetic rats had a lower number. There were no gender differences in number of cleaved caspase 3 stained Schwann cells, but rats with diabetes exhibited more (such cleaved caspase 3 stained Schwann) cells both at the lesion site and in the distal part of the sciatic nerve. Axonal outgrowth correlated with the number of ATF3 stained Schwann cells, but not with blood glucose levels or the cleaved caspase 3 stained Schwann cells. However, the number of cleaved caspase 3 stained Schwann cells correlated with the blood glucose level.
CONCLUSIONS
We conclude that there are gender differences in nerve regeneration in healthy rats and in type 2 diabetic GK rats.
背景
鉴于全球糖尿病发病率上升，且近期研究结果表明糖尿病性神经病变在男性中更为常见，评估糖尿病神经再生中的性别差异至关重要。我们的目的是在短期实验中评估健康和基因发育的2型糖尿病Goto-Kakizaki（GK）大鼠轴突生长的性别差异，并研究坐骨神经损伤和修复后活化的（即ATF-3，活化转录因子3）和凋亡的（裂解的半胱天冬酶3）雪旺细胞之间的联系。将自发发展为2型糖尿病的雌性和雄性糖尿病GK大鼠与相应的健康Wistar大鼠进行比较。切断坐骨神经并立即修复。六天后，收获神经以测量轴突生长（即神经丝染色），并使用免疫组织化学定量ATF-3（即活化的）和裂解的半胱天冬酶3（即凋亡的）染色的雪旺细胞数量。
结果
雄性大鼠的轴突生长通常比雌性大鼠长，健康大鼠的轴突生长也比糖尿病大鼠长。在远端神经节段和损伤部位附近，活化的雪旺细胞数量存在差异。特别是雌性糖尿病大鼠的数量较少。裂解的半胱天冬酶3染色的雪旺细胞数量没有性别差异，但糖尿病大鼠在损伤部位和坐骨神经远端都表现出更多（这种裂解的半胱天冬酶3染色的雪旺）细胞。轴突生长与ATF3染色的雪旺细胞数量相关，但与血糖水平或裂解的半胱天冬酶3染色的雪旺细胞无关。然而，裂解的半胱天冬酶3染色的雪旺细胞数量与血糖水平相关。
结论
我们得出结论，健康大鼠和2型糖尿病GK大鼠的神经再生存在性别差异。
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