Effect of erigeron breviscapus on relieving acute ocular hypertension and protecting retinal ganglion cells in glaucoma rats based on mitogen activated protein kinase signaling pathway_Chinese Journal of Ocular Fundus Diseases

Authors：

Ran Wenying , Zhu Dongmei ,  Wang Yuan

Department of Ophthalmology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China;

Corresponding author：

Wang Yuan, Email: cheng8852xiang@163.com

Keywords：

Erigeron breviscapus; Ocular hypertension; p38 mitogen-activated protein kinases; Retinal ganglion cells

DOI：

10.3760/cma.j.cn511434-20210407-00181

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Objective To investigate the effect of erigeron breviscapus (EBHM) on ocular hypertension and the protective effect of retinal ganglion cells (RGCs) in rats by regulating mitogen activated protein kinase (MAPK) signaling pathway.Methods Sixty male Sprague-Dawley rats were divided into control group, model group, low-dose EBHM group (group A), medium-dose EBHM group (group B), and high-dose EBHM group (group C) by random number table method. There were 12 rats in the group, the left eye was used as the experimental eye. The rats of model group, group A, group B, and group C were infused with normal saline through the anterior chamber to construct an acute ocular hypertension model; the control group was given general anesthesia only. Then, 2-30 days after modeling, rats in the control group and model group were given 3 ml of normal saline once a day; rats in group A, group B, and group C were given 0.30, 0.45, and 0.60 g/100 g EBHM by intragastric administration, respectively, 1 time/d. The rat intraocular pressure was measured before modeling and 1, 14, and 30 days after modeling, and the proportion of high intraocular pressure model was measured. Thirty days after modeling, hematoxylin-eosin (HE) staining was used to observe the pathological changes of retinal tissue; immunofluorescence staining was used to detect the changes in the number of RGCs; real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect p38 in the retinas of rats in each group. The relative expression of MAPK and Caspase-3 mRNA; western blot was used to detect p38MAPK and phosphorylation in the retina of rats in each group relative expression of phosphorylate-p38MAPK (p-p38MAPK) and Caspase-3 protein. One-way analysis of variance was used for multi-sample comparison, and SNK-q test was used for comparison between two samples.Results One day after modeling, none of the rats in the control group developed acute ocular hypertension, and the other groups were successfully modeled. Compared with the model group, the rates of acute ocular hypertension at 14 days after modeling in groups B and C were lower (χ²=98.701, P＜0.05), and the rates of acute ocular hypertension at 30 days after modeling in groups A, B, and C were 0. There was no statistically significant difference in the rates of acute ocular hypertension between 14 and 30 days after modeling in the A, B, and C groups (P＞0.05). The results of HE staining showed that the structure of the retina in the control group was complete, and the layers were clearly visible; the RGCs count was not abnormal, and the morphology was plump and round. The retina of rats in the model group became thinner; the number of RGCs was greatly reduced, the morphology was vacuolated, and the arrangement was sparse. The retina of rats in groups A, B, and C became thicker, and the number of RGCs increased, and the retina structure in group C was better restored. The results of immunofluorescence staining showed that the RGCs counts of rats in groups A, B, and C were higher than those in the model group, and the difference was statistically significant (F=297.514, P＜0.05); pairwise comparison between groups, group A was lower than that of group B and C Group (q=2.842, 5.263), group B was lower than group C (q=2.457), the difference was statistically significant (P＜0.05). The results of RT-qPCR and Western blot showed that compared with the model group, the relative expression of Caspase-3 mRNA (F=267.912) and protein (F=692.279) and the relative expression of p-p38MAPK protein in the retina of rats in groups A, B and C. The expression level (F=150.061) all decreased, and the difference was statistically significant (P＜0.05); pairwise comparisons between groups showed that Caspase-3 mRNA (q=6.977, 15.642) and protein (q=6.997, 15.642) relative expression levels and p-p38MAPK protein (q=12.443, 24.358) relative expression levels are lower than groups A and B, group B was lower than group A (q=11.678, 12.471, 10.204), the difference was statistical academic significance (P＜0.05).Conclusions EBHM can significantly reduce intraocular pressure in rats with acute ocular hypertension, increase RGCs counts, and reduce retinal damage. Its regulatory mechanism may be related to the MAPK pathway.

Citation： Ran Wenying, Zhu Dongmei, Wang Yuan. Effect of erigeron breviscapus on relieving acute ocular hypertension and protecting retinal ganglion cells in glaucoma rats based on mitogen activated protein kinase signaling pathway. Chinese Journal of Ocular Fundus Diseases, 2021, 37(6): 455-461. doi: 10.3760/cma.j.cn511434-20210407-00181 Copy

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1. Vithayathil J, Pucilowska J, Landreth GE. ERK/MAPK signaling and autism spectrum disorders[J]. Prog Brain Res, 2018, 241: 63-112. DOI: 10.1016/bs.pbr.2018.09.008.
2. Liu G, Tang G, Liang W, et al. PK-PD correlation of Erigeron breviscapus injection in the treatment of cerebral ischemia-reperfusion injury model rats[J]. J Mol Neurosci, 2021, 71(2): 302-324. DOI: 10.1007/s12031-020-01651-3.
3. 郭欣, 林珊, 吴丽明, 等. 灯盏细辛化学成分及药理作用研究进展[J]. 中成药, 2019, 41(2): 393-402. DOI: 10.3969/j.issn.1001-1528.2019.02.030.Guo X, Lin S, Wu LM, et al. Advances in studies on chemical constituents and pharmacological effects of Erigeron breviscapus[J]. Chinese Traditional Patent Medicine, 2019, 41(2): 393-402. DOI: 10.3969/j.issn.1001-1528.2019.02.030.
4. 武燕, 马秋艳, 杨迎新, 等. 肝失疏泄大鼠模型眼压和眼压波动[J]. 中国中医眼科杂志, 2019, 29(4): 262-265. DOI: 10.13444/j.cnki.zgzyykzz.2019.04.002.Wu Y, Ma QY, Yang YX, et al. Intraocular pressure and its fluctuation in rat model with liver failure in dredging and regulation syndrome[J]. Chinese Journal of Chinese Ophthalmology, 2019, 29(4): 262-265. DOI: 10.13444/j.cnki.zgzyykzz.2019.04.002.
5. Wang P, Huang H, Chen B, et al. Systems pharmacology dissection of mechanisms of Dengzhan Xixin injection against cardiovascular diseases[J]. Chem Pharm Bull (Tokyo), 2020, 68(9): 837-847. DOI: 10.1248/cpb.c20-00122.
6. Guo YJ, Pan WW, Liu SB, et al. ERK/MAPK signalling pathway and tumorigenesis[J]. Exp Ther Med, 2020, 19(3): 1997-2007. DOI: 10.3892/etm.2020.8454.
7. 何理烨, 梁亮, 朱梦男, 等. 鼠尾草酸对急性高眼压模型大鼠视网膜神经节细胞的保护作用[J]. 中华实验眼科杂志, 2018, 36(4): 254-258. DOI: 10.3760/cma.j.issn.2095-0160.2018.04.005.He LY, Liang L, Zhu MN, et al. Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats model[J]. Chin J Exp Ophthalmol, 2018, 36(4): 254-258. DOI: 10.3760/cma.j.issn.2095-0160.2018.04.005.
8. Lu M, Wang Y, Zhan X. The MAPK pathway-based drug therapeutic targets in pituitary adenomas[J/OL]. Front Endocrinol (Lausanne), 2019, 10: 330[2019-05-22]. https://pubmed.ncbi.nlm.nih.gov/31231308/. DOI: 10.3389/fendo.2019.00330.
9. Zhang W, Chen M, Meng HL, et al. Molecular cloning and expression analysis of SRLK1 gene in self-incompatible asteraceae species Erigeron breviscapus[J]. Mol Biol Rep, 2019, 46(3): 3157-3165. DOI: 10.1007/s11033-019-04773-z.
10. Li ZJ, Liu YY, Yang CW, et al. The complete chloroplast genome sequence of erigeron breviscapus and erigeron multiradiatus (asteraceae)[J]. Mitochondrial DNA B Resour, 2019, 4(2): 3826-3827. DOI: 10.1080/23802359.2019.1683478.
11. 彭涛, 于丹丹, 谢美娜, 等. 黄芪多糖对高眼压大鼠视网膜神经节细胞凋亡的影响[J]. 中国临床药理学杂志, 2020, 36(10): 1344-1346. DOI: 10.13699/j.cnki.1001-6821.2020.10.047.Peng T, Yu DD, Xie MN, et al. Effects of astragalus polysaccharides on retinal ganglion cell apoptosis in rats with high intraocular pressure[J]. The Chinese Journal of Clinical Pharmacology, 2020, 36(10): 1344-1346. DOI: 10.13699/j.cnki.1001-6821.2020.10.047.
12. Yang Y, Liu M, Zhang W, et al. Identification and characterization of two new 1-O-Acyl-glucose-ester forming glucosyltransferases from erigeron breviscapus[J]. J Agric Food Chem, 2019, 67(10): 2848-2855. DOI: 10.1021/acs.jafc.8b07215.
13. 张莹莹, 李智冬, 蒋楠, 等. 黄芩苷在小鼠急性高眼压视神经损伤中的作用及机制研究[J]. 中华眼科杂志, 2020, 56(5): 376-382. DOI: 10.3760/cma.j.cn112142-20200107-00011.Zhang YY, Li ZD, Jiang N, et al. Effect and mechanism of Baicalin on optic nerve injury induced by acute ocular hypertension in mice[J]. Chin J Ophthalmol, 2020, 56(5): 376-382. DOI: 10.3760/cma.j.cn112142-20200107-00011.
14. He S, Dong X, Zhang G, et al. High quality genome of erigeron breviscapus provides a reference for herbal plants in asteraceae[J]. Mol Ecol Resour, 2021, 21(1): 153-169. DOI: 10.1111/1755-0998.13257.

Chinese Journal of Ocular Fundus Diseases

Effect of erigeron breviscapus on relieving acute ocular hypertension and protecting retinal ganglion cells in glaucoma rats based on mitogen activated protein kinase signaling pathway

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