Dept of Endocrinology, Pathophysiology and Applied Biology, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.
Exp Neurol. 2011 Apr;228(2):215-21. doi: 10.1016/j.expneurol.2011.01.005. Epub 2011 Jan 15.
Clinical observations suggest a sex-dimorphism in the incidence and symptomatology of diabetic neuropathy, but this possible gender effect has never been investigated in detail in a well-characterized experimental model such as streptozotocin (STZ)-induced diabetes. Therefore, in this study we have compared with a multimodal set of tests the impact of diabetes on the sciatic nerve in male and female rats. To assess whether sex-dimorphism in peripheral diabetic neuropathy is dependent on gonadal hormones we have also analyzed the effect of ovariectomy and orchidectomy on the sciatic nerve of STZ-diabetic rats. Nerve conduction velocity (NCV), Na(+),K(+)-ATPase activity, expression of myelin proteins, thermal sensitivity and reactive oxygen species production were similarly affected in male and female animals by STZ. However, ovariectomy, but not orchidectomy, significantly counteracted STZ-induced alterations on NCV, Na(+),K(+)-ATPase activity, and expression of myelin proteins. This effect of ovariactomy was associated to an increase in the levels of neuroactive steroids, such as dehydroepiandrosterone, testosterone and dihydrotestosterone, in the sciatic nerve of diabetic rats. These neuroactive steroids have been demonstrated to be protective agents in this experimental model of diabetic neuropathy. However, their efficacy has been so far tested only in male animals. Therefore, the present data might represent an important background to evaluate their efficacy also in female diabetic animals.
临床观察表明，糖尿病性神经病的发病率和症状在性别上存在差异，但这种可能的性别效应在链脲佐菌素（STZ）诱导的糖尿病等特征明确的实验模型中从未被详细研究过。因此，在这项研究中，我们使用多种测试方法比较了糖尿病对雄性和雌性大鼠坐骨神经的影响。为了评估周围性糖尿病神经病的性别差异是否依赖于性腺激素，我们还分析了卵巢切除术和睾丸切除术对 STZ 糖尿病大鼠坐骨神经的影响。神经传导速度（NCV）、Na(+)、K(+)-ATP 酶活性、髓鞘蛋白表达、热敏感性和活性氧物质的产生在雄性和雌性动物中均受到 STZ 的相似影响。然而，卵巢切除术而非睾丸切除术显著拮抗了 STZ 引起的 NCV、Na(+)、K(+)-ATP 酶活性和髓鞘蛋白表达的改变。这种卵巢切除术的作用与神经活性甾体水平的增加有关，如在糖尿病大鼠的坐骨神经中，脱氢表雄酮、睾酮和二氢睾酮等神经活性甾体的水平增加。这些神经活性甾体已被证明是这种糖尿病性神经病实验模型中的保护剂。然而，迄今为止，它们的疗效仅在雄性动物中进行了测试。因此，目前的数据可能为评估它们在雌性糖尿病动物中的疗效提供重要背景。
