ABSTRACT
Objective To investigate the relationship between glycoprotein synthase kinase-3 (GSK-3β) and mitochondrial cleavage protein (Drp-1) during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.Methods Clean-grade healthy male Sprague-Dawley rats,weighing 250-300 g,were used in this study.Diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 30 g/kg.Forty rats with diabetes mellitus were divided into 5 groups (n =8 each) using a random number table method:ischemia-reperfusion (I/R) group,sevoflurane postconditioning group (SP group),sevoflurane postconditioning plus Drp1 inhibitor Mivi-1 group (SM group),sevoflurane postconditioning plus GSK-3β inhibitor SB216763 group (SB group) and sevoflurane postconditioning plus Mivi-1 plus SB216763 group (SMB group).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled 2.5％ sevoflurane for 10 min starting from 5 min before reperfusion in SP,SM,SB and SBM groups.Mivi-1 1.2 mg/kg was injected via the caudal vein at 15 min before reperfusion in group SM.SB216763 0.2 mg/kg was injected via the caudal vein at 5 min before reperfusion in group SB.Mivi-1 1.2 mg/kg and SB216763 0.2 mg/kg were injected via the caudal vein at 15 and 5 min before reperfusion,respectively,in group SMB.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of serum cardiac troponin Ⅰ (cTnⅠ) concentrations.The rats were sacrificed and myocardial specimens were obtained from the apex for determination of the cell apoptosis (by TUNEL) and expression of caspase-3 (by Western blot),and apoptotic index (AI) was calculated.Results Compared with group I/R,no significant change was found in caspase-3 expression,AI or serum cTnⅠ concentrations (P＞0.05),and the pathological changes of myocardium were comparable in group SP,and the expression of caspase-3 was significantly down-regulated,and AI and serum cTnⅠ concentration were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SP,the expression of caspase-3 was significantly down-regulated,AI and serum cTnⅠ concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SMB or group SB,the expression of caspase-3 was significantly down-regulated,AI and serum cTnI concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group SMB.Conclusion It is not a single regulatory relationship between GSK-3β and Drp-1 in the pathophysiological process of diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.
ABSTRACT
Objective To evaluate the effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats.Methods Sixty clean healthy male Sprague-Dawley rats,aged 18 months,weighing 350-500 g,were divided into 3 groups (n=20 each) using a random number table:control group (group C),sleep deprivation group (group D) and ulinastatin group (group U).Sleep deprivation was induced by using modified multiple platform method in D and U groups,and then splenectomy was performed in three groups.Ulinastatin 100 U/g was intraperitoneally injected before sleep deprivation and immediately after operation in group U.Ten rats were randomly selected at 3 days after operation and sacrificed,and hippocampi were removed for determination of the contents of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.Morris water maze test was performed at 3-7 days after operation in the rest ten rats in each group,and the escape latency and time of staying at the original platform were recorded.Results Compared with group C,the escape latency was significantly prolonged at 4-6 days after operation,the time of staying at the original platform was shortened,and the contents of IL-1β,IL-6 and TNF-α were increased at 3 days after operation in D and U groups (P＜0.05).Compared with group D,the escape latency was significantly shortened at 4-6 days after operation,the time spent in the original platform was prolonged,and the contents of IL-1β,IL-6 and TNF-α were decreased at 3 days after operation in group U (P＜0.05).Conclusion Ulinastatin can mitigate postoperative cognitive dysfunction in preoperative sleep deprived aged rats,which is related to inhibiting inflammatory responses.