山莨菪碱对心搏骤停猪心肺复苏后肺损伤的保护作用及其作用机制研究

Protective Effect and Its Mechanism of Anisodamine on Lung Injury after CPR in Pigs with Sudden Cardiac Arrest

目的探究山莨菪碱对心搏骤停猪心肺复苏(CPR)后肺损伤的保护作用及其作用机制。方法选择健康雄性家猪23头,按照随机数字表法分为假手术组(A组,n=5)、肾上腺素组(B组,n=9)和山莨菪碱+肾上腺素组(C组,n=9)。采用交流电致颤法建立心搏骤停模型。A组家猪只切开左颈外静脉,不进行致颤及CPR;B组和C组家猪制备心搏骤停模型后立即进行CPR,同时B组家猪注射肾上腺素,C组家猪注射肾上腺素+山莨菪碱。ROSC成功家猪和A组家猪在基础时点、心搏骤停8 min、自主循环恢复(ROSC)即刻、ROSC 30 min和ROSC 24 h留取血液标本,检测血浆肿瘤坏死因子α(TNF-α)和白介素6(IL-6)水平;ROSC 24 h处死所有家猪,留取肺组织标本,检测超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)、TNF-α及IL-6含量,肺含水量及湿/干重比(W/D);光镜下观察肺组织形态学变化。结果(1)B组和C组家猪均成功致颤,心电图均表现为心室纤颤。B组ROSC成功7头,C组ROSC成功5头。(2)基础时点3组家猪血浆TNF-α水平比较,差异无统计学意义(P>0.05);心搏骤停8 min、ROSC即刻、ROSC 30 min及ROSC 24 h B组和C组家猪血浆TNF-α水平低于A组,ROSC即刻、ROSC 30 min及ROSC 24 h C组家猪血浆TNF-α水平低于B组(P<0.05)。基础时点、心搏骤停8 min及ROSC即刻3组家猪血浆IL-6水平比较,差异无统计学意义(P>0.05);ROSC 30 min及ROSC 24 h B组和C组家猪血浆IL-6水平高于A组,ROSC 24 h C组家猪血浆IL-6水平低于B组(P<0.05)。(3)B组和C组家猪肺组织SOD含量低于A组,肺组织MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量高于A组(P<0.05)。C组家猪肺组织SOD含量高于B组,肺组织MDA含量、MPO含量、W/D、肺含水量及TNF-α含量低于B组(P<0.05)。(4)光镜下显示,B组家猪肺泡壁毛细血管扩张,肺泡渗出增多,炎性细胞浸润;而C组家猪上述表现明显减轻。结论山莨菪碱可能通过抑制TNF-α、IL-6过度释放,减轻脂质过氧化等来减轻心搏骤停猪CPR后肺损伤,进而发挥保护作用。

Objective To investigate the protective effect and its mechanism of anisodamine on lung injury after CPR in pigs with sudden cardiac arrest.Methods A total of 23 healthy male pigs were divided into A group（n = 5）,B group（n= 9）and C group（n = 9）according to random number table.Alternating current-induced ventricular fibrillation method was used to prepare the animal models of sudden cardiac arrest.Pigs of A group only received incision of left external carotid vein,did not received alternating current-induced ventricular fibrillation or CPR; pigs of B group and C group received immediate CPR after preparation of sudden cardiac arrest models,and pigs of B group received extra injection of epinephrine,while pigs of C group received extra injection of epinephrine and anisodamine.Blood specimens of successful ROSC pigs and A group were collected to detect the plasma levels of TNF-α and IL-6 at basis point,after 8 minutes of sudden cardiac arrest,at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC.After 24 hours of ROSC,all of the pigs were killed and lung tissue samples were collected to detect the SOD,MDA,MPO,TNF-α and IL-6 contents,water content and wet / dry weight ratio（W/D）.Light microscope was used to observe the morphological features of lung tissue.Results（1）Pigs of B group and C group were all successfully induced ventricular fibrillation affirmed by electrocardiogram.Of B group,7 pigs got successful ROSC;of C group,5 pigs got successful ROSC.（2）No statistically significant differences of plasma TNF-α level was found among the three groups at basis point（P〉0.05）; plasma TNF-α level of B group,C group was statistically significantly lower than that of A group after 8 minutes of sudden cardiac arrest,at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC,respectively,and plasma TNF-α level of C group was statistically significantly lower than that of B group at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC,respectively（P〈0.05）.No statistically significant differences of plasma IL-6 level was found among the three groups at basis point,after 8 minutes of sudden cardiac arrest or at once of ROSC（P〉0.05）; plasma IL-6 level of B group,C group was statistically significantly higher than that of A group after 30 minutes of ROSC and after 24 hours of ROSC,respectively,and plasma IL-6 level of C group was statistically significantly lower than that of B group after 24 hours of ROSC（P〈0.05）.（3）SOD content of lung tissue of B group,C group was statistically significant lower than that of A group,respectively,while MDA,MPO,TNF-α,IL-6 contents,water content and W / D of B group and C group were statistically significantly higher than those of A group（P〈0.05）; SOD content of lung tissue of C group was statistically significant higher than that of B group,while MDA,MPO,TNF-α water content and W / D of C group were statistically significantly lower than those of B group（P〈0.05）.Light microscope found alveolar walls capillaries expanded,alveoli exudation elevated and infiltration of inflammatory cells of B group,while above features of C group were relatively relieved.Conclusion Anisodamine can relieve lung injury after CPR in pigs with sudden cardiac arrest through inhibiting the excessive release of TNF-α and IL-6,alleviating of lipid peroxidation,and eventually play a role of protective effect.