ABSTRACT
Objective To evaluate the effect of isoflurane on the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and β-catenin in neural stem cells (NSCs) in the hippocampus of developing rats.Methods Twenty-four 7-day-old Sprague-Dawley rats,weighing 15-20 g,were divided into 2 groups (n =12 each) using a random number table:control group (group C) and 2％ isoflurane group (group Ⅰ).Group C inhaled 30％ oxygen for 4 h.Group Ⅰ inhaled 2％ isoflurane in 30％ oxygen for 4 h.Six rats were randomly selected from each group,and 5-bromodeoxyuridine (BrdU) 200 mg/kg was intraperitoneally injected immediately before anesthesia to assess the proliferation of NSCs in the hippocampal dentate gyrus.The rats were sacrificed at 6 h after the end of anesthesia,and hippocampi were isolated for determination of the number of BrdU positive cells in the dentate gyrus (by immunohistochemistry) and expression of p-GSK-3β and β-catenin in hippocampal tissues (by Western blot analysis).Results Compared with group C,the number of BrdU positive cells was significantly decreased,and the expression of p-GSK-3β and β-catenin was down-regulated in group Ⅰ (P＜0.05).Conclusion Isoflurane can inhibit the proliferation of NSCs in the hippocampal dentate gyrus of developing rats,and the mechanism may be related to down-regulation of the expression of p-GSK-3β and β-catenin.
ABSTRACT
Objective To investigate the role of high mobility group protein box 1 (HMGB1) in pulmonary vascular remodeling in a rat model of acute lung injury (ALI).Methods Thirty healthy pathogen free male Wistar rats weighing 220-250 g were randomly divided into 3 groups (n =10 each) ∶ group control (group C) ;group LPS (group M) and group LPS + HMGB1 antibody (group H).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 7 ml/kg.ALI was induced with LPS 1 mg/kg infused iv over 30 min in groups M and H.In group H HMGB1 antibody 2 mg/kg was injected iv at 12,24 and 36 h after LPS administration respectively.The animals were sacrificed at 72 h after LPS administration.The left lung was removed for microscopic examination,measurement of the thickness of the medial layer (tunica media) of pulmonary arterioles and determination of the expression of PCNA (by immune-histochemistry) and HMGB1 protein (by Western blotting).Results The medial layer of pulmonary arterioles was significantly thicker and the expression of PCNA and HMGB1 higher in group M than in group C.LPS also induced significant inflammatory cell infiltration within the alveoli and damage to the septa.In group H HMGB1 antibody significantly attenuated the above-mentioned LPS-induced changes.Conclusion HMGB1 may play an important role in the LPS-induced pulmonary vascular remodeling.