王洪宇，裴存文，法 利，段运动

（承德市中心医院眼科，河北承德 067000）

曲伏前列素致高眼压模型大鼠结膜充血的不良反应机制研究

王洪宇＊，裴存文#，法 利，段运动

（承德市中心医院眼科，河北承德 067000）

目的：研究曲伏前列素致高眼压模型大鼠结膜充血的不良反应机制。方法：将50只大鼠随机分为正常对照组、模型组和曲伏前列素低、中、高剂量组（100、200、400 mg/kg），每组10只。除正常对照组外，其余各组大鼠右眼建立高眼压模型，每天滴加相应药物1次，连续1周。末次给药后体外分离并培养各组大鼠右眼角膜周围血管内皮细胞，检测血管内皮细胞活力、细胞凋亡情况和增殖相关因子（Ki-76）、凋亡相关因子（Bad、Bax）、凋亡抑制相关因子（Bcl-2、Bcl-xl）蛋白表达水平。结果：与正常对照组比较，模型组大鼠血管内皮细胞活力明显降低，凋亡率明显增加，Bad、Bax蛋白表达明显增强，Bcl-2、Bcl-xl、Ki-76蛋白表达明显减弱，以上差异均有统计学意义（P＜0.05或P＜0.01）。与模型组比较，曲伏前列素低、中、高剂量组大鼠血管内皮细胞活力明显降低，凋亡率明显增加，Bcl-2、Bcl-xl蛋白表达明显减弱，以上差异均有统计学意义（P＜0.05或P＜0.01）；曲伏前列素中、高剂量组大鼠血管内皮细胞中Bad、Bax蛋白表达明显增强（P＜0.05或P＜0.01），其余指标差异均无统计学意义（P＞0.05）。结论：曲伏前列素可能是通过促进高眼压模型大鼠角膜周围血管内皮细胞凋亡，从而降低其细胞活力，进而引发结膜充血这一不良反应。

曲伏前列素；高眼压；血管内皮细胞；不良反应；结膜充血；大鼠

ABSTRACTOBJECTIVE：To study the ADR mechanism of conjunctival hyperemia in model rats with prostacyclin-induced high intraocular pressure.METHODS：50 rats were randomly divided into normal control group，model group，prostacyclin low-dose，medium-dose，high-dose groups（100，200，400 mg/kg），10 in each group.Except for normal control group，right eyes of rats in other groups were established high intraocular pressure model，dropping corresponding medicine once a day，for 1 week.After last administration，the right eyes cornel peripheral corneal endothelial cells of rats in each group were isolated in vitro and cultured.Vascular endothelial cell viability，cell apoptosis and proliferation-related factor（Ki-76），apoptosis-related factors（Bad，Bax），inhibito of apoptosis-related factors（Bcl-2，Bcl-xl）protein expressions were detected.RESULTS：Compared with normal control group，vascular endothelial cell viability in model group were obviously decreased；apoptosis rate was obviously increased；Bad，Bax protein expressions were obviously enhanced；Bcl-2，Bcl-xl，Ki-76 protein expressions were obviously weakened，with statistical significances（P＜0.05 or P＜0.01）.Compared with model group，vascular endothelial cell viability in prostacyclin low-dose，medium-dose，high-dose groups were obviously decreased；apoptosis rate was obviously increased；Bcl-2，Bcl-xl protein expressions were obviously weakened，with statistical significances（P＜0.05 or P＜0.01）；the Bad，Bax protein expressions in prostacyclin medium-dose，high-dose groups were obviously enhanced（P＜0.05 or P＜0.01），the other indexes had no statistical differences（P＞0.05）.CONCLUSIONS：Prostacyclin may cause conjunctival hyperemia through promoting the apoptosis of cornel peripheral corneal endothelial cells of model rats with high intraocular pressure and decreasing the cell viability.

KEYWORDSProstacyclin；High intraocular pressure；Vascular endothelial cell；ADR；Conjunctival hyperemia；Rats

青光眼发病率高，为不可逆及不可修复的致盲性疾病，其病理特征为眼内压力持续性升高导致眼球内部组织及功能受损，视网膜神经节细胞凋亡、坏死，视乳头损伤及进行性视野缺损[1-4]。……