目的 探討加蘭他敏介導(dǎo)核因子E2相關(guān)因子2(Nrf2)/血紅素氧合酶-1(HO-1)信號通路對慢性高眼壓大鼠視網(wǎng)膜神經(jīng)節(jié)細胞(RGCs)損傷的影響及其機制。方法 48只SD大鼠隨機分為假手術(shù)組、模型組、加蘭他敏組、加蘭他敏+ML385組,每組12只。假手術(shù)組大鼠進行手術(shù)操作但不烙閉鞏膜靜脈,其余各組大鼠采用鞏膜上靜脈烙閉法建立慢性高眼壓大鼠模型。加蘭他敏組大鼠ip 4 mg/kg加蘭他敏溶液;加蘭他敏+ML385組大鼠ip 4 mg/kg加蘭他敏溶液和30 mg/kg ML385。采用便攜式動物眼壓計測定眼壓;蘇木精-伊紅(HE)染色觀察視網(wǎng)膜組織形態(tài)及RGCs數(shù)量;TUNEL染色檢測RGCs凋亡情況;試劑盒法檢測視網(wǎng)膜組織中丙二醛(MDA)、超氧化物歧化酶(SOD)和過氧化氫酶(CAT)水平;Western blotting法檢測視網(wǎng)膜組織中Nrf2、HO-1蛋白表達。結(jié)果 與模型組相比,加蘭他敏組大鼠眼壓降低,視網(wǎng)膜組織病理損傷得到改善,RGCs數(shù)量增多,RGCs凋亡率降低,視網(wǎng)膜組織中SOD、CAT活性以及Nrf2、HO-1蛋白表達水平均升高,MDA含量降低(P<0.05)。與加蘭他敏組相比,加蘭他敏+ML385組大鼠眼壓升高,視網(wǎng)膜組織病理損傷加重,RGCs數(shù)量減少,RGCs凋亡率升高,視網(wǎng)膜組織中SOD、CAT活性以及Nrf2、HO-1蛋白表達水平均降低,MDA含量顯著升高(P<0.05)。結(jié)論 加蘭他敏可能通過激活Nrf2/HO-1信號通路減輕慢性高眼壓大鼠RGCs損傷。

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

新疆維吾爾自治區(qū)自然科學(xué)基金資助項目(2022D01C312)