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区域性表达的活性 MMP3 导致急性视网膜缺血/再灌注损伤后神经节细胞层中神经元的选择性丢失。

Regional Expression of Act-MMP3 Contributes to the Selective Loss of Neurons in Ganglion Cell Layers following Acute Retinal ischemia/Reperfusion Injury.

机构信息

Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, People's Republic of China.

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

出版信息

Curr Eye Res. 2020 May;45(5):591-603. doi: 10.1080/02713683.2019.1684523. Epub 2019 Nov 6.

Abstract

: Evidences suggest that during ischemia/reperfusion events, neuronal loss in ganglion cell layers (GCLs) occurs initially in the peripheral retinae followed by the central. However, which key molecule or factor mediates this selective loss needs elucidation. In the present study, we detected the regional expression of active matrix metalloproteinase 3 (Act-MMP3) in the central and peripheral rat retinae following acute retinal ischemia/reperfusion (RI/R) injury and explored the effects and mechanisms of this regional expression on the selective neuronal loss in GCLs.: QPCR and Western Blotting were used to detect the expression of Act-MMP3 in the central part and peripheral part of the adult rat retinae. Immunofluorescence and double immunofluorescence were used to assess the number of NeuN-positive cells in the GCLs and Iba-1+CD 68-positive cells were determined. Additionally, the Linear-regression analysis was performed to test the correlation between the ODV of Act-MMP3 and the neuronal loss in the GCLs/Iba-1+CD 68 positive cells in retinae.: An evident up-regulation of active matrix metalloproteinase 3 (Act-MMP3) in peripheral retinae preceded to that in central region following acute RI/R. We found Act-MMP3 up-regulation to be associated with the selective neuronal loss in GCLs (central: = 0.7566, < .0001, = 0.5724; peripheral: r = 0.8241, < .0001, r = 0.6792). Suppressing Act-MMP3 ameliorated the selective neuronal loss in GCLs following acute RI/R. Furthermore, the activation of microglia in the peripheral retinae also preceded to that in the central and was found to be correlated with the regional expression of Act-MMP3 (Central: = 0.8540, < .0001, = 0.7294; Peripheral: = 0.7820, < .0001, = 0.6116). Suppressing Act-MMP3 ameliorated the microglia regional activation following acute RI/R.: The regional expression of Act-MMP3 in the rat retinae may contribute to the selective neuronal loss in GCLs and microglia regional activation in acute RI/R.

摘要

: 有证据表明,在缺血/再灌注事件中,神经节细胞层(GCL)中的神经元最初在外周视网膜丢失,然后是中央视网膜。然而,介导这种选择性丢失的关键分子或因素仍需要阐明。在本研究中,我们检测了急性视网膜缺血/再灌注(RI/R)损伤后大鼠中央和外周视网膜中活性基质金属蛋白酶 3(Act-MMP3)的区域表达,并探讨了这种区域表达对 GCL 中选择性神经元丢失的影响及其机制。: 采用 QPCR 和 Western Blotting 检测成年大鼠视网膜中央部和周边部 Act-MMP3 的表达。采用免疫荧光和双重免疫荧光检测 GCL 中 NeuN 阳性细胞的数量,并测定 Iba-1+CD 68 阳性细胞数。此外,进行线性回归分析以检验 Act-MMP3 的 ODV 与视网膜 GCLs/Iba-1+CD 68 阳性细胞中神经元丢失的相关性。: 急性 RI/R 后,外周视网膜中活性基质金属蛋白酶 3(Act-MMP3)的明显上调先于中央区域。我们发现 Act-MMP3 的上调与 GCL 中选择性神经元丢失有关(中央:r = 0.7566, <.0001,r = 0.5724;外周:r = 0.8241, <.0001,r = 0.6792)。抑制 Act-MMP3 可改善急性 RI/R 后 GCL 中选择性神经元丢失。此外,外周视网膜中小胶质细胞的激活也先于中央视网膜,并与 Act-MMP3 的区域表达相关(中央:r = 0.8540, <.0001,r = 0.7294;外周:r = 0.7820, <.0001,r = 0.6116)。抑制 Act-MMP3 可改善急性 RI/R 后小胶质细胞的区域性激活。: 大鼠视网膜中 Act-MMP3 的区域表达可能导致 GCL 中选择性神经元丢失和急性 RI/R 中小胶质细胞的区域性激活。

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