瘦素介导硫化氢对 6-羟多巴胺诱导的帕金森病的保护作用：涉及增强瓦博格效应。
Leptin mediates protection of hydrogen sulfide against 6-hydroxydopamine-induced Parkinson's disease: Involving enhancement in Warburg effect.
机构信息
Institute of Neurology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China.
Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China.
出版信息
Neurochem Int. 2020 May;135:104692. doi: 10.1016/j.neuint.2020.104692. Epub 2020 Feb 4.
BACKGROUND
Hydrogen sulfide (HS) has therapeutic effects on Parkinson's disease (PD). Warburg effect, namely aerobic glycolysis, is benefit to PD. Leptin, a hormone secreted in adipose, plays an important role in the treatment of PD.
OBJECTIVE
To determine whether the mechanism underlying protection of HS against PD is involved in promoting Warburg effect via upregulation of leptin.
METHODS
We set a PD model via unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in Sprague Dawley rat. PD-like behavior was analyzed by apomorphine-induced rotations, open field activity test, stepping test and cylinder test. Dopaminergic neurons were detected by immunohistochemistry. The expressions of Hexokinase-2, pyruvate kinase M-2, lactate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, and leptin were measured by Western blot. Lactate dehydrogenase (LDHA) activity was monitored by ELISA. The lactate content was measured by lactate assay kit.
RESULTS
We showed that NaHS (a donor of HS) prevented 6-OHDA-induced PD-like behaviors as well as the loss of dopaminergic neurons. We also found that NaHS enhanced the Warburg effect and upregulated leptin expression in the substantia nigra of 6-OHDA-exposed rats. While, inhibited leptin signaling by OBR13-A reversed the protections of HS against 6-OHDA-exerted PD-like behaviors and the loss of dopaminergic neurons in the substantia nigra, and abolished HS-enhanced in the Warburg effect in the substantia nigra.
CONCLUSION
These data indicated that leptin mediates the protection of HS against PD, which involves enhancing the Warburg effect of the substantia nigra.
背景
硫化氢（HS）对帕金森病（PD）有治疗作用。Warburg 效应，即有氧糖酵解，有利于 PD。瘦素是脂肪分泌的一种激素，在 PD 的治疗中起着重要作用。
目的
确定 HS 对 PD 的保护作用机制是否涉及通过上调瘦素来促进 Warburg 效应。
方法
我们通过向 Sprague Dawley 大鼠单侧纹状体注射 6-羟多巴胺（6-OHDA）建立 PD 模型。通过阿扑吗啡诱导旋转、旷场活动试验、踏步试验和圆筒试验分析 PD 样行为。免疫组织化学检测多巴胺能神经元。Western blot 检测己糖激酶-2、丙酮酸激酶 M-2、乳酸脱氢酶、丙酮酸脱氢酶激酶、丙酮酸脱氢酶和瘦素的表达。通过 ELISA 监测乳酸脱氢酶（LDHA）活性。通过乳酸测定试剂盒测量乳酸含量。
结果
我们表明，NaHS（HS 的供体）可预防 6-OHDA 诱导的 PD 样行为以及多巴胺能神经元的丢失。我们还发现，NaHS 增强了 6-OHDA 暴露大鼠黑质中的 Warburg 效应并上调了瘦素表达。然而，通过 OBR13-A 抑制瘦素信号转导可逆转 HS 对 6-OHDA 引起的 PD 样行为和黑质中多巴胺能神经元丢失的保护作用，并消除 HS 增强的黑质中的 Warburg 效应。
结论
这些数据表明，瘦素介导了 HS 对 PD 的保护作用，涉及增强黑质的 Warburg 效应。
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