title: Midazolam inhibits the apoptosis of astrocytes induced by oxygen glucose deprivation via targeting JAK2-STAT3 signaling pathway.
abstract: BACKGROUND
  There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition.
  
  
  METHODS
  The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10 μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay.
  
  
  RESULTS
  Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ.
  
  
  CONCLUSIONS
  Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.
authors.affiliation: Department of Anesthesiology, the Third Hospital of Harbin Medical University, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: You
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Tu
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Li
authors.forename: Lihong
authors.initials: L
authors.lastname: Zheng
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.forename: Guonian
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism; D008874:Midazolam / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D051028:bcl-2-Associated X Protein; D053614:Janus Kinase 2; D053148:Caspase 3; D005947:Glucose; D008874:Midazolam