Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats
Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats
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DOI：
10.1080/01616412.2016.1232013
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发表时间：
2016-01-01
影响因子：
1.9
通讯作者：
Asil, Talip
中科院分区：
文献类型：
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作者：
Altintas, Ozge;Altintas, Mehmet Ozgen;Asil, Talip
目的：在本研究中，我们旨在评估缺血预处理（IPreC）对糖尿病大鼠短暂性大脑中动脉闭塞（MCAo）脑卒中脑部miRNA表达谱的影响。方法：80只雄性Spraque Dawley大鼠被分为8组。为了评估 miRNA 的表达谱，我们在 STZ 诱导糖尿病 (DM) 7 天后诱导短暂的 MCAo。我们还在短暂性MCAo前72小时进行了IPreC，以评估IPreC是否对缺血再灌注损伤具有神经保护作用。结果：与非糖尿病大鼠相比，STZ治疗的大鼠的一般特征包括体重减轻和血糖水平升高。我们证明了 miRNA 表达谱的生物学功能，如水通道蛋白 4 形成（miR-29b-2、miR-124a-3p、miR-130a、miR-223 和 miR-320a）、谷氨酸毒性（miR107、miR-145、miR-223）、可挽救缺血区域（miR-9a、miR-19b、 miR-29b-2、miR-341、miR-339-5p、miR-15-5p、miR-99b-5p）和新血管生成（let-7f-5p、miR-126a 和 miR-322-3p）在 IPreC 后受到调节。与其他组相比，脑缺血前的缺血预处理显着减少了梗死面积[IPreC + MCAo (27 +/- 11 mm(3)) vs. MCAo (109 +/- 15 mm(3)) p < 0.001； DM + IPreC + MCAo (38 +/- 9 mm(3)) 与 DM + MCAo (165 +/- 41 mm(3)) p < 0.001，分别]。讨论：研究结果揭示了缺血预处理的神经保护作用，并得到 MCA 梗塞中上调的促生存 miRNA 的支持。
Objectives: In this study, we aimed to evaluate the effect of the Ischemic preconditioning (IPreC) on the expression profile of cerebral miRNAs against stroke by induced transient middle cerebral artery occlusion (MCAo) in diabetic rats.Methods: Eighty male Spraque Dawley rats were allocated to eight groups. In order to evaluate the expression profile of miRNAs, we induced transient MCAo seven days after STZ-induced diabetes (DM). Also we performed IPreC 72 h before transient MCAo to assess whether IPreC could have a neuroprotective effect against ischemia-reperfusion injury.Results: The general characteristics of STZ-treated rats included reduced body weight and elevated blood glucose levels compared to non-diabetic ones. We demonstrated that miRNA expression profiles, which are determined for biological functions such as aquaporin 4 formation (miR-29b-2, miR-124a-3p, miR-130a, miR-223 and miR-320a), glutamate toxicity (miR107, miR-145, miR-223), salvageable ischemic area (miR-9a, miR-19b, miR-29b-2, miR-341, miR-339-5p, miR-15-5p, miR-99b-5p), and neoangiogenesis (let-7f-5p, miR-126a and miR-322-3p), were regulated following IPreC. Ischemic preconditioning before cerebral ischemia significantly reduced infarction size compared with the other groups [ IPreC + MCAo (27 +/- 11 mm(3)) vs. MCAo (109 +/- 15 mm(3)) p < 0.001; DM + IPreC + MCAo (38 +/- 9 mm(3)) vs. DM + MCAo (165 +/- 41 mm(3)) p < 0.001, respectively].Discussion: The study results revealed the neuroprotective effects of ischemic preconditioning, supported with the upregulated pro-survival miRNAs in MCA infarcts.