Effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion in mice:the role of TGF-β1 in brain tissues / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion (Ⅰ/R) in mice and the role of transforming growth factor-beta 1 (TGF-β1) in brain tissues.Methods Sixty healthy SPF male C57BL/6J mice,weighing 23-25 g,aged 8-10 weeks,were divided into 5 groups (n =12 each) using a random number table method:sham operation group (group Sham),Ⅰ/R group,dexmedetomidine group (group D),dexmedetomidine plus IgG1 isotype control monoclonal antibody group (group DI) and dexmedetomidine plus TGF-β1 neutralizing monoclonal antibody group (group DA).Cerebral Ⅰ/R was induced by occlusion of the middle cerebral artery followed by reperfusion.Dexmedetomidine 50 μg/kg was intraperitoneally injected every 24 h for 14 days starting from 14 days of reperfusion in group D.TGF-β1 neutralizing monoclonal antibody 20 μg and IgG1 isotype control monoclonal antibody 20 μg were intraperitoneally injected at 30 min prior to dexmedetomidine injection in group DA and group DI,respectively.5-bromodeoxyuridine (BrdU) 100 mg/kg was intraperitoneally injected and injected again at an 8-h interval on 27 days of reperfusion.Forced swimming test (FST),sucrose consumption test (SCT) and open field test (OFT) were performed at 16 h after the second administration of BrdU.After the end of behavior testing,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone on ischemic side was measured by immunohistochemistry,and the expression of TGF-β1 protein and mRNA in brain tissues in ischemic area was detected using Western blot and real-time polymerase chain reaction,respectively.Results Compared with group Sham,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group Ⅰ/R (P＜0.05 or 0.01).Compared with group Ⅰ/R,the time spent floating in FST was significantly shortened,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were increased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group D (P＜0.05 or 0.01).Compared with group D,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was decreased in group DA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group DI (P＞0.05).Conclusion Dexmedetomidine can relieve depression and anxiety following cerebral Ⅰ/R,thus promotes nerve regeneration and the mechanism is related to up-regulating the expression of TGF-β1 in brain tissues of mice.