Page 54 - 《中国药房》2023年15期

阿魏酸钠对角膜内皮功能障碍及CEC损伤的影响及潜在机制 Δ

宋 辉 ，姚为华，余晨曦，舒百全，刘 易，韦 康（黄冈市中心医院眼科，湖北 黄冈 438000）
＊

中图分类号 R965；R772.21 文献标志码 A 文章编号 1001-0408（2023）15-1840-07
DOI 10.6039/j.issn.1001-0408.2023.15.10

摘 要 目的 探讨阿魏酸钠（SF）对角膜内皮功能障碍及角膜内皮细胞（CEC）损伤的影响及潜在机制。方法 将雄性新西兰兔分
为对照组、苯扎氯铵（BAK）组和BAK+SF组，每组6只。除对照组外，其余组以前房注射BAK建立大泡性角膜病变模型，BAK+SF
组于术后次日腹腔注射SF溶液200 mg/kg，每天2次，连续14 d。观察各组兔角膜透明度和基质水肿情况（术前及术后第1、7、14
天），检测其角膜厚度（术后第14天）和眼内压（术后第1～14天）；于术后第14天，评估其角膜内皮结构并检测功能相关蛋白[鬼笔
环肽、胞质紧密连接蛋白1（ZO-1）、钠钾ATP酶、Ki67]的表达情况。于术后14 d采集BAK组角膜组织，分离、培养原代兔CEC，将
其分为空白组和不同质量浓度 SF 组，检测不同培养时间下各组细胞的活力和 Ras 同源基因家族 A（RhoA）、骨形成蛋白受体 1A
（BMPR1A）、BMRP2蛋白的表达情况。结果 与BAK组比较，BAK+SF组兔角膜透明度和基质水肿情况逐渐好转，且角膜厚度显
著减小（P＜0.05）；其CEC仅缺损至B区，且表现为正常的六边形内皮细胞结构；其角膜内皮组织中鬼笔环肽、ZO-1、钠钾ATP酶、
Ki67蛋白的表达均显著升高（P＜0.05）。当SF质量浓度≤200 mg/L时，其对兔CEC的增殖有一定的促进作用，具有浓度依赖性
（P＜0.05）和时间依赖趋势，且 50、100、200 mg/L 的 SF 可浓度依赖性地上调细胞中 RhoA、BMPR1A、BMPR2 蛋白的表达（P＜
0.05）。结论 SF可改善大泡性角膜病变模型兔受损角膜内皮的透明度，减轻基质水肿，减小角膜厚度，维持角膜内皮结构完整性
并促进角膜内皮功能恢复；该成分还可促进兔CEC的增殖，此作用可能与激活RhoA-Rho激酶-骨形成蛋白信号通路有关。
关键词 阿魏酸钠；角膜内皮细胞；大泡性角膜病变；Ras同源基因家族A-Rho激酶-骨形成蛋白信号通路

Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury
SONG Hui，YAO Weihua，YU Chenxi，SHU Baiquan，LIU Yi，WEI Kang（Dept. of Ophthalmology， Huanggang
Central Hospital， Hubei Huanggang 438000， China）

ABSTRACT OBJECTIVE To investigate the effect and potential mechanism of sodium ferulate （SF） on corneal endothelial

dysfunction and corneal endothelial cell （CEC） injury. METHODS The male New Zealand rabbits were divided into control group，
benzalkonium chloride （BAK） group and BAK+SF group， with 6 rabbits in each group. Except for control group， the other groups
were given BAK into the anterior chamber to induce bullous keratopathy model， and BAK+SF group then given SF solution 200
mg/kg intraperitoneally the next day after surgery， twice a day， for consecutive 14 d. The transparency of corneal and edema of
corneal stroma in each group of rabbits （before and on the 1st， 7th， and 14th day after surgery） were observed， and the corneal
thickness （14th day after surgery） and intraocular pressure （1st to 14th day after surgery） were measured. On the 14th day after
operation， the corneal endothelial structure was evaluated and the expressions of functionally related proteins [phalloidin， zonula
occludens-1 （ZO-1）， Na /K -ATPase， Ki67] were detected. On the 14th day after surgery， the corneal tissue was collected in BAK
+
+
group， the primary rabbit CECs were isolated and cultured， and they were divided into blank group and SF groups with different
mass concentrations. The cell viabilities after being cultured for different time， and the protein expressions of Ras homologous gene
family A （RhoA）， bone morphogenetic protein receptor 1A （BMPR1A） and BMRP2 were determined in each group. RESULTS
Compared with BAK group， the transparency of corneal and edema of corneal stroma were gradually improved， and the corneal
thickness was significantly decreased in BAK+SF group （P＜0.05）. The rabbit CECs in BAK+SF group were only damaged to zone
B and showed a normal hexagonal endothelial cells structure. The protein expressions of phalloidin， ZO-1， Na /K -ATPase and Ki67
+
+
in BAK+SF group were significantly increased （P＜0.05）. When SF concentration was lower than and equal to 200 mg/L， it could
promote the proliferation of rabbit CEC， in concentration manner （P＜0.05） and time-dependent trend. SF at concentrations of 50，
100， and 200 mg/L could up-regulate the protein expressions of RhoA， BMPR1A and BMPR2 in concentration-dependent manner
（P＜0.05）. CONCLUSIONS SF can improve the transparency of corneal and edema of corneal stroma in bullous keratopathy
model rabbits， reduce corneal thickness， maintain the integrity of corneal endothelium structure， and promote the recovery of
corneal endothelial function； this compound can promote the proliferation of CEC， the mechanism of which may be related to the
activation of RhoA-ROCK-BMP pathway.
Δ 基金项目 湖北省卫生计生科研项目（No.WJ2020F087）
＊第一作者 主治医师。研究方向：玻璃体视网膜疾病。E-mail： KEYWORDS sodium ferulate； corneal endothelial cells；
songhui8264@163.com bullous keratopathy； RhoA-ROCK-BMP pathway

· 1840 · China Pharmacy 2023 Vol. 34 No. 15 中国药房 2023年第34卷第15期