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

宋辉; 姚为华; 余晨曦; 舒百全; 刘易; 韦康

doi:10.6039/j.issn.1001-0408.2023.15.10

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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

药学研究 | 更新时间：2023-08-10

- 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
- Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury
- 中国药房 2023年34卷第15期页码：1840-1846
- 作者机构：
  
  黄冈市中心医院眼科，湖北黄冈　438000
- 作者简介：
  
  主治医师。研究方向：玻璃体视网膜疾病。E-mail：songhui8264@163.com
- 基金信息：
  
  湖北省卫生计生科研项目(WJ2020F087)
- DOI：10.6039/j.issn.1001-0408.2023.15.10
  中图分类号： R965;R772.21
- 纸质出版日期：2023-08-15，
  
  收稿日期：2022-12-20，
  
  修回日期：2023-05-31，
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宋辉,姚为华,余晨曦等.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[J].中国药房,2023,34(15):1840-1846.

SONG Hui,YAO Weihua,YU Chenxi,et al.Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury[J].ZHONGGUO YAOFANG,2023,34(15):1840-1846.
宋辉,姚为华,余晨曦等.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[J].中国药房,2023,34(15):1840-1846. DOI： 10.6039/j.issn.1001-0408.2023.15.10.

SONG Hui,YAO Weihua,YU Chenxi,et al.Effect and potential mechanism of sodium ferulate on corneal endothelial dysfunction and CEC injury[J].ZHONGGUO YAOFANG,2023,34(15):1840-1846. 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（

＜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（

＜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（

＜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（

＜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。

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

-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 （

＜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

-ATPase and Ki67 in BAK+SF group were significantly increased （

＜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 （

＜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 （

＜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.

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

Keywords

corneal endothelial cellsbullous keratopathyRhoA-ROCK-BMP pathway

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