基于 JAK2/STAT3 通路分析姜黄素对视网膜缺血-再灌注损伤大鼠视网膜小胶质细胞极化的影响

Translated title of the contribution: Analysis of the effect of Curcumin on retinal microglia polarization of rats with retinal ischemia reperfusion injury via janus kinase 2/signal transducer and activator of transcription 3 pathway

Yi Yin, Ying Xu, Yuze Zhao, Chenxu Wang, Peilun Xiao, Xiaoshuang Li, Xiaoli Wang, Yansong Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To explore the effect of Curcumin (CUR) on the retinal microglia polarization in retinal ischemia reperfusion injury (RIRI) rats and analyze its mechanism via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, providing the theoretical basis for the clinical application of CUR. Methods Totally 36 healthy male adult Sprague Dawley rats were randomly divided into the Sham group, RIRI group and CUR group, with 12 in each group. The RIRI models were established in the right eye of rats in the RIRI group and CUR group by the high intraocular pressure method. In the Sham group, the needle was only inserted into the anterior chamber of the right eye without increasing intraocular pressure. At 30 min before the modeling, rats in the CUR group were intraperitoneally injected with CUR (100 mg·kg-1), while rats in the RIRI group and Sham group were intraperitoneally injected with an equal dose of physiological saline. At 24 h after modeling, the retinal morphology and the number of retinal ganglion cells (RGC) of rats in each group were observed by hematoxylin-eosin (HE) staining and immunohistochemical staining. Iba-1/CD16 and Iba-1/Arg1 immunofluorescence staining was used to detect the effect of CUR on the polarization of retinal microglia in RIRI rats. Immunohistochemical staining combined with Western blot was used to observe the effect of CUR on the expression of RGC and the molecular expression of JAK2/STAT3 signaling pathway in RIRI rats. Results The HE staining and immunohistochemical staining showed that the retinal cells of rats in the Sham group were neatly arranged, and a large number of Brn-3a+ cells (that is, RGC) were found in the ganglion cell layer. Compared with the Sham group, the thickness of the inner retinal layer increased significantly, and the number of RGC decreased significantly in the RIRI group 24 h after modeling; the thickness of the inner retinal layer in the CUR group was significantly thinner than that in the RIRI group, and the number of RGC was significantly higher than that in the RIRI group (all P < 0. 05). The double immunofluorescence labeling staining showed that the number of Iba-1+ CD16+ cells (M1 microglia) in the RIRI group was significantly higher than that in the Sham group, while the number of retinal Iba-1+ CD16+ cells in the CUR group was significantly less than that in the RIRI group, but still more than that in the Sham group (all P < 0. 05). The number of Iba-1+ Arg1+ cells (M2 microglia) in the RIRI group significantly increased compared with that in the Sham group, while the number of Iba-1+ Arg1+ cells in the CUR group was significantly higher than that in the RIRI group (both P < 0. 05). Immunohistochemical staining results showed that the numbers of porcine-janus kinase 2 (p-JAK2)+ and porcine-signal transducer and activator of transcription 3 (p-STAT3)+ cells in the RIRI group were higher than those in the Sham group, while the numbers of p-JAK2+ and p-STAT3+ cells in the CUR group were significantly lower than those in the RIRI group (all P < 0. 05). The Western blot detection results showed that the protein expression levels of p-JAK2 and p-STAT3 in the Sham group were lower; at 24 h after modeling, the protein expression levels of p-JAK2 and p-STAT3 increased significantly in the RIRI group, while those in the CUR group were significantly lower than the RIRI group, but still higher than the Sham group (all P < 0. 05). Conclusion CUR can regulate the microglia polarization from M1 to M2, so as to alleviate RIRI of rats and show neuroprotective effects. Its mechanism may be related to the activation of the JAK2/STAT3 signaling pathway.

Translated title of the contributionAnalysis of the effect of Curcumin on retinal microglia polarization of rats with retinal ischemia reperfusion injury via janus kinase 2/signal transducer and activator of transcription 3 pathway
Original languageChinese (Traditional)
Pages (from-to)439-443
Number of pages5
JournalRecent Advances in Ophthalmology
Volume43
Issue number6
DOIs
StatePublished - Jun 2023
Externally publishedYes

Keywords

  • Curcumin
  • janus kinase 2/signal transducer and activator of transcription 3 pathway
  • microglia polarization
  • retina ischemia reperfusion injury

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