Li Jing-bo, Lu Zhi-gang, Xu Li, Wang Qi, Zhang Zu-hai, Fang Jia-hua
Department of Ophthalmology, First Hospital of Jingzhou, Yangtze University, Jingzhou, 434000, Hubei, China.
Cell Biochem Biophys. 2014 Mar;68(2):275-82. doi: 10.1007/s12013-013-9707-4.
The retinal ischemia-reperfusion model has been studied extensively and is an ideal animal model for studying clinical situations such as acute glaucoma and optic neuropathy. Our previous reports showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced retinal ganglion cells damage through the drug's anti-NMDA receptor effects. Here, we investigated whether bis(7)-tacrine protects the retina from ischemic injury in a rat model. Retinal ischemia was induced by raising the intraocular pressure to 120 mmHg for 90 min. Rats received intraperitoneal injections of 0.2 mg/kg bis(7)-tacrine or saline at 30 min before ischemia, and then twice a day after retinal ischemia. Morphometric evaluation showed that bis(7)-tacrine dramatically reduced the retinal damage compared with the control group. Moreover, bis(7)-tacrine suppressed ischemia-induced reductions in a- and b-wave amplitudes of electroretinography. Protein levels of p53, the tumor suppressor gene known to induce apoptosis, were increased after ischemic injury, and treatment with bis(7)-tacrine reduced the expression of the protein. Our results suggest that bis(7)-tacrine has a neuroprotective effect against ischemic injury in the rat retina, possibly through the drug's anti-apoptotic effects. Bis(7)-tacrine may potentially be useful as a therapeutic drug in the management of ischemic retinal diseases.
视网膜缺血再灌注模型已得到广泛研究，是用于研究急性青光眼和视神经病变等临床情况的理想动物模型。我们之前的报告显示，双（7）-他克林通过其抗N-甲基-D-天冬氨酸（NMDA）受体作用，对谷氨酸诱导的视网膜神经节细胞损伤具有神经保护作用。在此，我们研究了双（7）-他克林是否能在大鼠模型中保护视网膜免受缺血性损伤。通过将眼压升至120 mmHg并维持90分钟来诱导视网膜缺血。在缺血前30分钟，大鼠腹腔注射0.2 mg/kg双（7）-他克林或生理盐水，视网膜缺血后每天注射两次。形态学评估显示，与对照组相比，双（7）-他克林显著减轻了视网膜损伤。此外，双（7）-他克林抑制了缺血诱导的视网膜电图a波和b波振幅降低。已知可诱导细胞凋亡的肿瘤抑制基因p53的蛋白水平在缺血性损伤后升高，而双（7）-他克林治疗降低了该蛋白的表达。我们的结果表明，双（7）-他克林可能通过其抗凋亡作用对大鼠视网膜缺血性损伤具有神经保护作用。双（7）-他克林可能有望作为治疗缺血性视网膜疾病的治疗药物。
