GRP94、EIF2α在原发型闭角性青光眼小梁中的作用研究
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摘要
目的通过检测内质网应激的相关因子GRP94、EIF2α在原发性慢性闭角型青光眼(PCACG)患者小梁组织中的表达,研究内质网应激在PCACG小梁组织氧化损伤中的作用,探讨PCACG的发病机制。方法分别用HE染色法观察实验组及对照组小梁组织镜下显微形态的变化、免疫组化法测定实验组及对照组小梁组织中内质网应激相关因子GRP94、 EIF2α的表达水平。结果 HE染色显示,PCACG患者小梁组织排列不规则,小梁网眼窄小,Schlemm管腔变窄且不规则。免疫组化结果显示,对照组的小梁网组织GRP94、EIF2α少量表达,实验组小梁组织中GRP94、EIF2α的表达明显增加,差异均具有统计学意义(P<0.05)。结论 PCACG患者小梁组织中存在内质网应激,内质网应激EIF2α通道参与了小梁组织的氧化损伤,促进了眼内压的升高。
Objective The aim of this study was to investigate the role of endoplasmic reticulum stress in trabecular tissue of patients with chronic primary angle-closure glaucoma(PCACG) and to explore its role in the pathogenesis of PCACG. Methods Hematoxylin and eosin(H& E) staining was used to observe changes in the microscopic morphology of trabeculae. Expression of the endoplasmic reticulum stress-related factors, GRP94 and EIF2α, in trabecular tissues, was determined by immunohistochemistry. Results H&E staining showed altered morphology of trabecular tissues, such as the narrow trabeculae and narrow lumen and irregular pigmentation of Schlemm's canal. Immunohistochemistry results showed that GRP94 and EIF2α were expressed in the trabecular tissue of the control group and their expression increased significantly in the experimental groups(P<0.05). Conclusion These results show that endoplasmic reticulum stress occurs in the trabecular tissue of PCACG patients. The EIF2α signaling pathway may participate in the oxidative damages of trabecular tissue and promote an increase in intraocular pressure.
Objective The aim of this study was to investigate the role of endoplasmic reticulum stress in trabecular tissue of patients with chronic primary angle-closure glaucoma(PCACG) and to explore its role in the pathogenesis of PCACG. Methods Hematoxylin and eosin(H& E) staining was used to observe changes in the microscopic morphology of trabeculae. Expression of the endoplasmic reticulum stress-related factors, GRP94 and EIF2α, in trabecular tissues, was determined by immunohistochemistry. Results H&E staining showed altered morphology of trabecular tissues, such as the narrow trabeculae and narrow lumen and irregular pigmentation of Schlemm's canal. Immunohistochemistry results showed that GRP94 and EIF2α were expressed in the trabecular tissue of the control group and their expression increased significantly in the experimental groups(P<0.05). Conclusion These results show that endoplasmic reticulum stress occurs in the trabecular tissue of PCACG patients. The EIF2α signaling pathway may participate in the oxidative damages of trabecular tissue and promote an increase in intraocular pressure.
引文
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[2]Feng JY,Chen XJ,Sun XJ,et al.Expression of endoplasmic reticulum stress markers GRP78 and CHOP induced by oxidative stress in blue light-mediated damage of A2E-containing retinal pigment epithelium cells[J].Ophthalmic Res,2014,52(4):224-233.doi:10.1159/000363387.
[3]朱玉广,王杰,朱艳,等.氧化应激介导的NF-κB信号通路对猪小梁细胞MMPs/TIMPs表达的作用研究[J].山东大学学报(医学版),2012,50(5):51-54,59.doi:10.6040/j.issn.1671-7554.2012.05.011.ZHU Yuguang,WANG Jie,ZHU Yan,et al.Role of the NF-κB signaling pathw ay mediated by oxidative stress in extracelluar matrix remodeling of trabecular meshw ork cells[J].Journal of Shandong University(Health Sciences),2012,50(5):51-54,59.doi:10.6040/j.issn.1671-7554.2012.05.011.
[4]孙宝琪,陈晨,李珺,等.氧化应激介导的NF-κB信号通路在人小梁细胞表达的作用研究[J].潍坊医学院学报,2015,37(4):262-264.doi:10.3969/j.issn.1004-3101.2015.04.006.SUN Baoqi,CHEN Chen,LI Jun,et al.The role of NF-κb signaling pathway mediated by oxidative stress in human trabecular meshw ork cells[J].Acta Academiae M edicinae Weifang,2015,37(4):262-264.doi:10.3969/j.issn.1004-3101.2015.04.006.
[5]陈晨,朱艳,李霞,等.过氧化氢对人小梁细胞内质网应激ATF4-CHOP通路的影响[J].潍坊医学院学报,2016,38(5):379-381.doi:10.16846/j.issn.1004-3101.2016.05.019.CHEN Chen,ZHU Yan,LI Xia,et al.The effect of H2O2 on endoplasmic reticulum stress ATF4-CHOP signaling pathw ay in human trabecular meshw ork cells[J].Acta Academiae M edicinae Weifang,2016,38(5):379-381.doi:10.16846/j.issn.1004-3101.2016.05.019.
[6]李珺,李霞,滕兴波,等.内质网应激在慢性闭角型青光眼小梁组织氧化损伤中作用研究[J].潍坊医学院学报,2017,39(5):336-338.doi:10.16846/j.issn.1004-3101.2017.05.006.LI Jun,LI Xia,TENG Xingbo,et al.The role of endoplasmic reticulum stress in trabecular meshw ork of primary chronic angle-closure glaucoma patients[J].Acta Academiae M edicinae Weifang,2017,39(5):336-338.doi:10.16846/j.issn.1004-3101.2017.05.006.
[7]Senft D,Ronai ZA.UPR,autophagy,and mitochondria crosstalk underlies the ER stress response[J].Trends Biochem Sci,2015,40(3):141-148.doi:10.1016/j.tibs.2015.01.002.
[8]Ren LP,Yu X,Song GY,et al.Impact of activating transcription factor 4 signaling on lipogenesis in Hep G2cells[J].M ol M ed Rep,2016,14(2):1649-1658.doi:10.3892/mmr.2016.5453.
[9]Han J,Murthy R,Wood B,et al.ER stress signalling through e IF2αand CHOP,but not IRE1α,attenuates adipogenesis in mice[J].Diabetologia,2013,56(4):911-924.doi:10.1007/s00125-012-2809-5.
[10]Pomar N,Berlanga J J,Campuzano S,et al.Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2alpha(e IF2alpha)kinase.[J].European Journal of Biochemistry,2003,270(2):293-306.