NRG 1β对缺血再灌注损伤大鼠视网膜细胞凋亡及Bax表达影响

2025-04-26

作者：徐建森孟瑞华张杰王景

【摘要】目的探讨神经调节蛋白1β （NRG1β）对大鼠视网膜缺血再灌注损伤后的保护作用及对Bax表达的影响。方法制备大鼠视网膜缺血再灌注模型。将33只Wistar大鼠随机分为正常组（3只）、对照组（15只）、实验组（15只），于缺血再灌注开始时实验组大鼠玻璃体腔注射5 μL的NRG1β，对照组大鼠玻璃体腔注射平衡盐溶液5 μL。用核苷酸末端转移酶介导的dUTP末端标记法检测视网膜神细胞凋亡的变化，同时利用免疫组化方法检测Bax表达情况的变化。结果凋亡细胞主要出现在视网膜内核层及神经节细胞层,而外核层几乎无阳性表达。与对照组比较，实验组再灌注各时间点视网膜细胞凋亡数目显著减少(t=2.57～6.25,P＜0.01)，实验组再灌注各时间点Bax蛋白的表达显著降低(t=3.84～11.97,P＜0.01)。结论 NRG1β对视网膜缺血再灌注损伤具有明显保护作用，NRG1β抑制Bax的表达可能是其抑制视网膜缺血再灌注损伤后细胞凋亡的机制之一。
【关键词】再灌注损伤；视网膜；神经调节蛋白类；bcl2相关X蛋白质
［ABSTRACT］ Objective To investigate the protection of neuregulin1β (NRG1β) on retinal cells after ischemical reperfusion injury and the effects of NRG1β on the expression of Bax protein. Methods A model of retinal ischemia reperfusion in rat was made. Thirtythree wistar rats were divided into three groups as normal (three rats), control (15 rats) and experimental (15 rats). An injection of 5 μL of NRG1β into vitreous cavity of the rats in experimental group was offered, and 5 μL of BSS in the control group. Retinal paraffin sections were stained with TdTmediated dUTP nick end labeling to examine the apoptosis of retinal cells. The expression of Bax was detected immunohistochemically. Results Apoptotic cells mainly appeared in the inner nuclear and the ganglion cell layers, almost no positive expression was seen in the outer nuclear layer. Compared with the control group, the numbers of apoptotic cells and eressions of Bax in various time points in experimental group were significantly lower(t=2.57－11.97,P<0.01). Conclusion NRG1β shows a significant protection for retina with ischemical reperfusion injury. The inhibition of Bax by NRG1β may be one of the mechanisms preventing the apoptosis of this kind of retinal cell injury.
    ［KEY WORDS］ Reperfusion injury; Retina; Neuregulins; Bcl2associated X protein
    视网膜缺血再灌注损伤（RIRI）是眼科临床上常见病理过程，也是目前缺血性眼病领域的研究热点，其实验动物模型的制备日臻成熟[1]，对缺血再灌注损伤机制的研究更全面，基因水平上的研究越来越完备，而最终针对各个可能的损伤机制而采取的保护和治疗措施正逐渐为我们所关注。有研究表明,早期的视网膜缺血再灌注是有益的,经过一定时间,缺血的视网膜并未出现明显功能障碍,但在再灌注后却出现了明显的功能障碍甚至不可逆损伤[2]。本研究利用线栓法制作RIRI模型，玻璃体腔注射神经调节蛋白1β（NRG1β）观察视网膜缺血再灌注前后Bax表达的情况,以探讨NRG1β及Bax在RIRI中的作用,为NRG1β对RIRI的治疗提供理论依据。现将结果报告如下。
    1       材料与方法

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