目的 探讨加兰他敏介导核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)信号通路对慢性高眼压大鼠视网膜神经节细胞(RGCs)损伤的影响及其机制。方法 48只SD大鼠随机分为假手术组、模型组、加兰他敏组、加兰他敏+ML385组,每组12只。假手术组大鼠进行手术操作但不烙闭巩膜静脉,其余各组大鼠采用巩膜上静脉烙闭法建立慢性高眼压大鼠模型。加兰他敏组大鼠ip 4 mg/kg加兰他敏溶液;加兰他敏+ML385组大鼠ip 4 mg/kg加兰他敏溶液和30 mg/kg ML385。采用便携式动物眼压计测定眼压;苏木精-伊红(HE)染色观察视网膜组织形态及RGCs数量;TUNEL染色检测RGCs凋亡情况;试剂盒法检测视网膜组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)水平;Western blotting法检测视网膜组织中Nrf2、HO-1蛋白表达。结果 与模型组相比,加兰他敏组大鼠眼压降低,视网膜组织病理损伤得到改善,RGCs数量增多,RGCs凋亡率降低,视网膜组织中SOD、CAT活性以及Nrf2、HO-1蛋白表达水平均升高,MDA含量降低(P<0.05)。与加兰他敏组相比,加兰他敏+ML385组大鼠眼压升高,视网膜组织病理损伤加重,RGCs数量减少,RGCs凋亡率升高,视网膜组织中SOD、CAT活性以及Nrf2、HO-1蛋白表达水平均降低,MDA含量显著升高(P<0.05)。结论 加兰他敏可能通过激活Nrf2/HO-1信号通路减轻慢性高眼压大鼠RGCs损伤。

Objective To investigate the effect of galanthamine mediated Nrf2/HO-1 signaling pathway on RGCs injury in rats with chronic ocular hypertension and its mechanism. Methods Forty-eight SD rats were randomly divided into sham operation group, model group, galanthamine group, galanthamine + ML385 group, with 12 rats in each group. The rats in the sham operation underwent surgical procedures without cauterizing the scleral veins, while the rats in the other groups used cauterization of the superior scleral veins to establish the chronic ocular hypertension rat model. Galanthamine group rats ip 4 mg/kg galanthamine solution, galantamine + ML385 group of rat ip 4 mg/kg galantamine solution and 30 mg/kg ML385. The intraocular pressure was measured by portable animal tonometer, retinal tissue morphology and the number of RGCs were observed by HE staining. The apoptosis of RGCs was detected by TUNEL staining, the levels of MDA, SOD, and CAT in retinal tissue were measured by kit method. The expression of Nrf2 and HO-1 proteins in retinal tissue were detected by Western blotting. Results Compared with the model group, the intraocular pressure was decreased of rats in galanthamine group, pathological damage of retinal tissue was improved, the number of RGCs were increased, the apoptosis rate of RGCs were decreased, the activities of SOD, CAT and the expression levels of Nrf2 and HO-1 proteins in retinal tissue were increased, while the content of MDA in retinal tissue was decreased (P < 0.05). Compared with the galanthamine group, the intraocular pressure was increased of rats in galanthamine + ML385 group, the pathological damage of retinal tissue was aggravated, the number of RGCs were decreased, the apoptosis rate of RGCs were increased, the activities of SOD, CAT and the expression levels of Nrf2 and HO-1 proteins in retinal tissue were decreased, while the content of MDA in retinal tissue was increased (P < 0.05). Conclusion Galanthamine may alleviate RGCs injury in chronic ocular hypertension rats by activating Nrf2/HO-1 signaling pathway.

R965

新疆维吾尔自治区自然科学基金资助项目(2022D01C312)