右旋美托咪定对脓毒血症大鼠心功能障碍的影响

Influence of dexmedetomidine on cardiac dysfunction in rats with sepsis

目的观察右旋美托咪定对脓毒血症大鼠心功能障碍的影响。方法 30只SD大鼠随机均分假手术(Sham)组、盲肠结扎穿孔(CLP)组和右旋美托咪定(Dex)组,每组各10只。采用盲肠结扎穿孔法建立大鼠脓毒血症模型。Dex组大鼠建模后即给予负荷量的右旋美托咪定7μg/kg,20 min后以5μg/(kg·h)持续泵注,其余两组均于术后持续泵注等量生理盐水。采集术后6 h、12 h、24 h时的平均动脉压(MAP)、心率(HR)、左心室舒张末压(LVEDP)、左心室收缩压(LVSP)、左心室最大收缩速率(+d P/dt),左室最大舒张速率(-d P/dt)。采用ELISA试剂盒法检测血清中血清脂联素、肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)水平。结果与Sham组比较,CLP组与Dex组大鼠在术后6 h、12 h和24 h的血流动力学指标MAP、HR、LVEDP、LVSP、+d P/dt和-d P/dt及24 h的血清脂联素、TNF-α及IL-1β水平均明显均明显降低(P<0.05)。与CLP组比较,Dex组大鼠在术后6 h、12 h和24 h的血流动力学指标MAP、HR、LVEDP、LVSP、+d P/dt及-d P/dt均明显升高(P<0.05),术后24 h时血清脂联素水平升高、TNF-α及IL-1β水平明显减少(P<0.05)。结论 Dex可明显改善脓毒血症大鼠心功能障碍并维持血流动力学稳定,其作用可能与上调血清脂联素表达水平、抑制TNF-α和IL-1β炎症因子表达,减轻脓毒症所致心脏毒性和心肌损伤有关。

Objective To observe the influence of dexmedetomidine on cardiac dysfunction in rats with sepsis. Methods SD rats（n=30） were randomly divided into sham-operation group（Sham group）, cecal ligation and puncture group（CLP group） and dexmedetomidine group（Dex group, each n=10）. The rat model of sepsis was established by applying CLP. Dex group was given load dose of Dex（7 μg/kg, and 5 μg/kg·h after 20 min）, and other 2 groups were given the same dose of normal saline solution. The changes of mean arterial pressure（MAP）, heart rate（HR）, LVEDP, LVSP, ＋d P/dt and-d P/dt were observed after CLP for 6 h, 12 h and 24 h respectively. The levels of serum adiponectin（ADP）, tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were detected by using ELISA. Results Compared with Sham group, MAP, HR, LVEDP, LVSP, ＋d P/dt and-d P/dt after 6 h, 12 h and 24 h, and levels of serum ADP, TNF-α and IL-1β after 24 h decreased significantly in CLP group and Dex group（P〈0.05）. Compared with CLP group, MAP, HR, LVEDP, LVSP, ＋d P/dt and-d P/dt after 6 h, 12 h and 24 h increased significantly（P〈0.05）, level of serum ADP increased and levels of TNF-α and IL-1β decreased significantly（P〈0.05） in Dex group after 24 h. Conclusion Dex can significantly relieve cardiac dysfunction and maintain stable hemodynamics in sepsis rats, and the effect maybe related to up-regulating serum ADP, inhibiting TNF-α and IL-1β, and abating sepsis-induced cardiotoxicity and myocardial injury.