TMP Prevents Retinal Neovascularization and Imparts Neuroprotection in an Oxygen-Induced Retinopathy Model
TMP Prevents Retinal Neovascularization and Imparts Neuroprotection in an Oxygen-Induced Retinopathy Model
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TMP 在氧诱导的视网膜病变模型中预防视网膜新生血管形成并提供神经保护
DOI：
10.1167/iovs.11-9315
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发表时间：
2012-04-01
影响因子：
4.4
通讯作者：
Min, Wang
中科院分区：
文献类型：
--
作者：
Liang, Xiaoling;Zhou, Huanjiao;Min, Wang
目的.观察川芎嗪（TMP）对氧诱导视网膜病变（OIR）模型视网膜新生血管（NV）的影响，并探讨其神经保护作用。新生C57 BL/6 J小鼠从出生后第7天（P7）至P12接受75%氧气，然后返回室内空气。从P12至P17每天给予TMP（200 mg/kg）或生理盐水。采用免疫组化、HE染色、TUNEL法、RT-PCR等方法观察川芎嗪对视网膜神经血管修复的影响。TMP通过促进修复毛细血管网边缘的内皮尖端细胞的形成和保存无血管视网膜中的星形胶质细胞模板，有效地预防病理性NV并加速生理性血管再生。TMP还通过拯救神经元如无长突细胞、视杆双极细胞、水平细胞和Muller细胞来防止无血管视网膜中的形态学变化并显著减少TUNEL阳性细胞。在TMP处理的小鼠视网膜中，无长突细胞体及其明显条带的损失不太明显;杆双极和水平细胞体的数量以及外丛状层中树突的密度均大于OIR对照小鼠。TMP不仅能减少Muller细胞胞体排列的丢失和突起的变形，而且还能减少Muller细胞GFAP的反应性表达。结论：TMP可下调HIF-1 α和VEGF mRNA的表达。TMP通过预防NV和保护视网膜星形胶质细胞和神经元免于缺血诱导的细胞死亡来改善神经血管恢复，部分原因是其下调HIF-1a和VEGF mRNA表达。（Invest Ophthalmol维斯科学。2012; 53：2157-2169）DOI：10.1167/iovs.11-9315
PURPOSE. To evaluate the effects of tetramethylpyrazine (TMP) on retinal neovascularization (NV) and neuroprotection in an oxygen-induced retinopathy (OIR) model.METHODS. Neonatal C57BL/6J mice were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. TMP (200 mg/kg) or normal saline was given daily from P12 to P17. Immunostaining, HE staining, TUNEL assay, and RT-PCR were used to assess the effects of TMP on retinal neurovascular repair.RESULTS. TMP effectively prevented pathologic NV and accelerated physiologic revascularization by enhancing the formation of endothelial tip cells at the edges of the repairing capillary networks and preserving the astrocytic template in the avascular retina. TMP also prevented morphologic changes and significantly decreased TUNEL-positive cells in the avascular retina by rescuing neurons such as amacrine, rod bipolar, horizontal, and Muller cells. In TMP-treated mice retinas, there was a less obvious loss of amacrine cell bodies and their distinct bands; the number of both rod bipolar and horizontal cell bodies, as well as the density of their dendrites in the outer plexiform layer, was greater than that in OIR control mice. TMP not only decreased the loss of alignment of Muller cell bodies and distortion of processes but reduced the reactive expression of GFAP in Muller cells. Furthermore, HIF-1 alpha and VEGF mRNA expression were downregulated in TMP-treated mice retinas.CONCLUSIONS. TMP improved neurovascular recovery by preventing NV and protecting retinal astroglia cells and neurons from ischemia-induced cell death partially due to its downregulation of HIF-1a and VEGF mRNA expression. (Invest Ophthalmol Vis Sci. 2012; 53:2157-2169) DOI:10.1167/iovs.11-9315