右美托咪啶对大鼠脓毒症转归的影响

目的 探讨右美托咪啶对大鼠脓毒症转归的影响.方法 健康雄性SD大鼠,周龄10～14周,体重260～390 g,采用盲肠结扎-穿孔法制备脓毒症模型.取模型制备成功的大鼠90只,随机分为3组(n=30):对照组(C组)、咪达唑仑组(M组)和右美托咪啶组(D组).术毕C组静脉输注生理盐水1 ml/h;M组静脉输注咪达唑仑0.6 mg·kg-1·h-1;D组静脉输注右美托咪啶5 μg·kg-1·h-1,各组均持续8 h.各组取10只大鼠,观察术后24 h内的生存情况;各组取10只大鼠,于术前、术后2、4、5 h时取颈动脉血样,采用ELISA法测定血浆肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的浓度;各组取10只大鼠,于术后8 h时测定肾功能.处死进行细胞因子和肾功能测定结束后未死亡的大鼠,取脾脏组织,采用Western blot法测定caspsse-3和泛素的表达.结果 与C组比较,M组和D组血浆TNF-α浓度降低,Na+排泄分数降低,脾脏组织caspase-3表达下调,泛素表达上调(P<0-05),血浆IL-6浓度和肌酐清除率差异无统计学意义(P>0.05);与M组比较,D组血浆TNF-α浓度降低(P<0.05),血浆IL-6浓度、Na+排泄分数、肌酐清除率、脾脏组织caspase-3和泛素的表达差异无统计学意义(P>0.05).C组、M组和D组术后24 h内生存率分别为10%、80%和90%.M组和D组术后24 h内生存率高于C组(P<0.05).结论 右美托咪啶可提高脓毒症大鼠的生存机率.

Effects of dexmedetomidine on outcome in rats with sepsis

Objective To investigate the effects of dexmedetomidine on the outcome in rats with sepsis. Methods Male SD rats, aged 10-14 weeks, weighing 260-390 g, were used in this study. Sepsis was induced by cecal ligation and puncture (CLP). Ninety rats of successful sepsis model were randomly divided into 3 groups ( n = 30 each) : control group (group C), midasolam group (group M) and dexmedetomidine group (group D). In group C, M and D, normal saline at a rate of 1 ml/h, midazolam at a rate of 0.6 mg·kg-1·h-1 and dexmedetomidine at a rate of 5 μg·kg-1·h-1 were infused iv for 8 h after operation respectively. Ten rats of each group were selected for observation of the survival condition during 24 h after operation. Another 10 rats of each group were selected and blood samples were taken from carotid artery before operation and at 2, 4 and 5 h after operation for measurement of plasma concentrations of TNF-α and IL-6 by ELISA. The remaining 10 rats of each group were selected at 8 h after operation for determination of the renal function. The rats still alive after the determination of cytokines and renal function were killed and spleen tissues were taken for determination of the expression of caspase-3 and ubiquitin by Western blot. Results Compared with group C, the plasma concentration of TNF-α and fractional excretion of sodium (FENa+) were significantly decreased, caspase-3 expression in spleen tissues was down-regulated and abiquitin expression in spleen tissues was up-regulated in group M and D ( P < 0.05), while there were no significant differences in plasma concentration of IL-6 and creatinine clearance rate (Ccr) at 8 h after operation between group M and C and between group D and C ( P > 0.05). The plasma concentration of TNF-α was significantly lower in group D than in group M ( P < 0.05), while there were no significant differences in plasma concentration of IL-6, FE Na+ , Ccr and expression of caspase-3 and ubiquitin in splen tissues between group D and M ( P>0.05). The survival rates during 24 h after operation were 10%, 80% and 90% in group C, M and D respectively. The survival rates during 24 h after operation were signifrcantly higher in group M and D than in group C ( P > 0.05). Conclusion Dexmedetomidine can raise the survival rate during sepsis.