y-39983预处理对缺血-再灌注损伤大鼠视网膜的保护作用
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Protection of y-39983 preconditioning from retinal ischemia-reperfusion injury in rats
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    摘要:

    目的:探讨ROCK抑制剂y-39983对缺血再灌注(ischemia reperfusion,IR)大鼠视网膜的保护作用。

    方法: SD大鼠60只随机分为正常组(n=15)、IR组(n=15)、生理盐水组(n=15)、y-39983治疗组(n=15)。正常组不做任何处理,后三组制作视网膜IR模型(前房加压灌注法),其中生理盐水组和y-39983治疗组于造模前5min分别向实验眼玻璃体腔内注入无菌生理盐水和y-39983各10μL。采用免疫组化方法检测细胞间黏附分子-1(intercellular cell adhesion molecules-1,ICAM-1)表达。荧光金逆行标记计数各组大鼠视网膜神经节细胞(retinal ganglion cells,RGCs)。应用组织病理学方法和视网膜电流图评估视网膜损伤程度。

    结果:y-39983预处理能降低 ICAM-1 蛋白表达和视网膜水肿程度,并且显著提高了视网膜神经节细胞存活率及b波和O2相对恢复率,缓解IR损伤所致的内层视网膜变薄的情况。

    结论:y-39983能减轻视网膜IR损伤,而这一保护效应在一定程度上与其抑制ICAM-1异常表达增加有关,表明y-39983对IR损伤相关的视网膜疾病有治疗作用。

    Abstract:

    AIM: To investigate the neuroprotective effect of rho-associated coiled coil-forming protein kinase(ROCK)inhibitor y-39983 on retinal ischemia reperfusion(IR)injury in rats.

    METHODS: Sixty adult SD rats were randomly assigned into normal group(n=15), IR group(n=15), saline group(n=15), y-39983 group(n=15), and the rats in later three groups were induced retinal IR by intra-anterior chamber infusion of saline solution. Rats in the saline and y-39983 groups were intravitreously injected with normal saline and y-39983 respectively, 5 minutes prior to the induction of ischemia. The protein expression of intercellular cell adhesion molecules-1(ICAM-1)was determined by immunohistochemical staining. Retrograde labeling of retinal ganalion cells(RGCs)with fluorogold was performed to assess the number of RGCs. Histologic studies and electroretinogram were carried out to evaluate retinal damage.

    RESULTS: The preadminisration of y-39983 decreased ICAM-1 expression, elevated the survival rate of RGCs and the recoverage rate of amplitude of b wave and O2 wave significantly, and attenuated the IR-induced the thinning of inner retina.

    CONCLUSION: y-39983 can protect the rat retina from IR injury at least partially by inhibiting ICAM-1 abnormal expression, suggesting that y-39983 may have therapeutic potential for the retinal diseases associated with IR.

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蒙青青,刘苏. y-39983预处理对缺血-再灌注损伤大鼠视网膜的保护作用.国际眼科杂志, 2013,13(7):1308-1313.

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  • 收稿日期:2013-04-25
  • 最后修改日期:2013-06-17
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  • 在线发布日期: 2013-07-01
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