不同剂量右美托咪定预处理对大鼠体外循环肺损伤的影响

Effects of different doses of dexmedetomidine on lung injury during cardiopulmonary bypass in rats

目的观察不同剂量右美托咪定预处理对大鼠体外循环肺损伤的影响。方法成年雄性大鼠随机分为6组(n=24):单纯开胸组(T组)、单纯CPB组(C组)、肺缺血再灌注组(IR组)、右美托咪定Ⅰ组(DexⅠ组1.5μg/kg)、右美托咪定Ⅱ组(DexⅡ组3μg/kg)、右美托咪定Ⅲ组(DexⅢ组6μg/kg);各组大鼠腹腔麻醉,股静脉穿刺置管连接大鼠膜式氧合器,股动脉穿刺置管连接生物信号采集处理系统监测生命体征。右颈总动脉穿刺置管连接蠕动泵,气管插管连接小动物呼吸机。在左侧第四肋间开胸,游离左肺门并夹闭,建立大鼠体外循环左肺缺血再灌注损伤模型。各组大鼠于CPB前(T1)、开放肺门即刻(T2)及停机后1.5h(T3)时点抽取血液进行血气分析并计算氧合指数(OI)、呼吸指数(RI);取左肺组织形态观察;TUNEL法测细胞凋亡;ELISA检测血清及肺组织中TNF-α、IL-1β、IL-6含量。结果随着时间的延长,T组各时点OI和RI无明显变化;其余各组各时间点OI:T1>T2>T3(P<0.05),RI变化则相反;OI和RI于IR、Dex I、Dex II、Dex III组间差异无统计学意义。T3时点:T组和C组肺损伤程度、凋亡程度和免疫组化评分均比其余各组轻;IR、DexⅠ、DexⅡ、DexⅢ组间差异无统计学意义。肺组织及血浆TNF-α、IL-1β、IL-6含量T组最少,C组次之,IR、DexⅠ、DexⅡ、DexⅢ各组间无明显差异,但明显高于T组、C组(P<0.05)。结论大鼠肺组织、血浆TNF-α、IL-1β、IL-6含量的增加,可能是导致CPB肺损伤的重要原因;不同剂量的右美托咪定预处理对CPB肺损伤没有明显的保护作用,具体原因还需要更深入的研究。

Objective To explore the protective effect of dexmedetomidine on lung injury during cardiopulmonary bypass（ CPB） in rats and whether different doses of dexmedetomidine have such protective effect,to find the optimal dose of dexmedetomidine. Methods Adult SD rats were randomly divided into 6 groups： simple operation group（ group T）,simple CPB group（ group C）,left lung ischemia-reperfusion injury of CPB group（ group IR）,dexmedetomidine I group（ group Dex Ⅰ 1. 5 μg/kg）,dexmedetomidine Ⅱ group（ group Dex Ⅱ 3 μg/kg））,and dexmedetomidine Ⅲ group（ group Dex Ⅲ 6 μg/kg）. Establish CPB left lung ischemia-reperfusion injury model. Arterial blood was collected before CPB（ T1）,at the onset of opening hilum（ T2） and 1. 5 h after CPB（ T3） to calculate oxygenation index（ OI） and respiration index（ RI）. Lung tissues were taken to measure following indexes. Hematoxylin-eosin staining was performed to observe the pathological changes. Paraffin sections were made to detect apoptosis with Td T-mediated d UTP Nick – End Labeling method（ TUNEL） and immunohistochemical score. The expression of TNF-α、IL-1β、IL-6 in lung tissue and serum was measured with enzyme linked immunosorbent assay method（ ELISA）. Results OI and RI are not significantly different between IR,DexⅠ,DexⅡ and DexⅢ groups. The severity of lung injury,the apoptosis degree and the immunohistochemical scores at T3 point showed the lowest levels in group T,followed by group C and group IR、Dex I、Dex II、Dex III,there was nothing different between group IR、Dex I、Dex II、Dex III. The levels of TNF-α,IL-1β and IL-6 also showed no significant difference between IR,Dex Ⅰ,Dex Ⅱ and Dex Ⅲ groups at all time points.Conclusion The increased content of TNF-α 、IL-1β、IL-6 in lung tissue of rat may be the important cause of lung injury after CPB; different doses of dexmedetomidine had no significant protective effect to lung injury after CPB,which needs further investigation.