促红细胞生成素对视网膜色素变性的RCS大鼠的作用

为观察促红细胞生成素对视网膜色素变性的RCS大鼠的作用,探讨其对视网膜变性神经元保护的可能机制。我们把出生后雄性RCS大鼠48只,随机分为给药组和对照组。RCS大鼠给药组从生后5d开始腹腔注射重组人促红细胞生成素(rhEPO),每5d注射一次,剂量为4000IU/kg。RCS大鼠对照组注射生理盐水,剂量同上。HE染色和TUNEL检测观察rhEPO对视网膜色素变性神经元的保护作用。应用免疫组织化学方法检测caspase2蛋白的表达。结果显示:(1)RCS大鼠给药组20d,25d,感光细胞的数目与对照组大鼠相比明显增加(P<0.05);(2)RCS大鼠给药组25dTUNEL检测阳性细胞数目与对照组相比,差异有统计学意义(P<0.05);(3)生后25d到40d,RCS大鼠给药组和对照组在节细胞层和内核层观察到caspase2阳性染色,RCS大鼠给药组在20d和25d内核层caspase2阳性细胞数目多于对照组(P<0.05)。结果提示:在RCS大鼠视网膜变性的早期,rhEPO对神经元起保护作用,可以使感光细胞得到更多存留;rhEPO对视网膜变性神经元的早期保护作用可能是通过抑制凋亡的方式进行的;caspase2蛋白在视网膜的一过性高表达提示其参与了视网膜感光细胞的凋亡过程,rhEPO可减少其早期的表达,对早期变性的神经元发挥保护作用。

THE EFFECT OF ERYTHROPOIETIN ON THE COURSE OF HEREDITARY RETINAL DYSTROPHY IN RCS RATS

To observe the therapeutic effects of erythropoietin (EPO) on experimental retinal degeneration, and to explore the possible protective mechanism of EPO. A total of 48 male RCS rats were divided into treatment and control groups randomly. 4000 IU/kg of rhEPO was injected intraperitoneally in treatment group from postnatal 5 days, once per 5 days. Similarly, saline was injected intraperitoneally in control group. Photoreceptor necrosis and apoptosis was assessed by the method of HE staining and TUNEL detection. The expression of caspase-2 was detected by immunohistochemistry. The results showed that (1) At postnatal 20 and 25 days, the number of photoreceptor of treatment group was more than that of control group (P<0.05). (2) At postnatal 25 days, the number of TUNEL-positive cells is obvious different between the treatment and control groups (P<0.05). (3) From postnatal 25 to 40 days, the caspase-2-positive cells were seen in the ganglion cell layer and inner nuclear layer in the treatment and control groups. The number of positive cells in the inner nuclear layer of treatment group was more than that of control group (P<0.05). The results suggest that rhEPO has the therapeutic effect on the early stage of retinal degeneration, which might make more photoreceptors preserved. RhEPO might preserve degenerated neurons in the early stage through inhibiting apoptosis. caspase-2 protein may have a role in the retinal degeneration and rhEPO might protect apoptotic neurons from inhibiting the expression of caspase-2.