S-烯丙基-L-半胱氨酸对大鼠脓毒症相关心肌损伤的影响及其与铜死亡的关系

Effect of S⁃ally⁃L⁃cysteine on sepsis⁃related myocardial injury in rats and its relationship with cuproptosis

目的:评价S-烯丙基-L-半胱氨酸(SAC)对大鼠脓毒症相关心肌损伤的影响及其与铜死亡的关系。方法:成年雄性SD大鼠(体重210~240 g)60只,采用随机数表法将大鼠分为假手术组、脓毒症心肌病组、SAC+脓毒症心肌病组。盲肠结扎穿刺术构建脓毒症模型。于脓毒症模型构建前1 h按照210 mg/kg的剂量将SAC腹腔注射给药。模型及干预制备成功后采用心电监测和右颈总动脉插管有创动脉监测记录各组大鼠心率(HR)、平均动脉压(MAP)和左室收缩压(LVSP)。采集动脉血和心肌组织样本检测CK-MB同工酶、SOD、ROS和铜离子水平。酶联免疫吸附(ELISA)法检测心肌组织TNF-α、IL-6、NF-κB和FDX1水平。苏木精-伊红(HE)染色检测心肌组织病理变化。结果:与假手术组相比,脓毒症心肌病组大鼠HR、MAP和LVSP水平降低(P<0.05),SOD水平降低(P<0.05),CK-MB同工酶、ROS、铜离子、TNF-α、IL-6、NF-κB和FDX1水平升高(P<0.05),脓毒症心肌病组大鼠心肌组织出现明显紊乱,心肌纤维肿胀或断裂,可见大量炎性细胞浸润。与脓毒症心肌病组大鼠相比,SAC+脓毒症心肌病组大鼠HR、MAP和LVSP水平升高(P<0.05),SOD水平升高(P<0.05),CK-MB同工酶、ROS、铜离子、TNF-α、IL-6、NF-κB和FDX1水平降低(P<0.05),心肌纤维紊乱情况、心肌纤维肿胀程度与心肌纤维断裂程度均减轻,炎性细胞浸润较少。结论:SAC可有效减轻脓毒症大鼠心肌损伤,其机制与SAC对心肌组织铜死亡的抑制作用相关。

Objective:To evaluate the effect of S⁃ally⁃L⁃cysteine(SAC)on sepsis⁃related myocardial dam⁃age in rats and its relationship with cuproptosis.Methods::Sixty adult male SD rats(weighing 210⁃240 g)were divided into sham operation group,septic cardiomyopathy group,and SAC+septic car⁃diomyopathy group by random number table method.A sepsis model was established by cecal ligation and puncture.SAC was administered intraperitoneally at a dose of 210 mg/kg one hour before the es⁃tablishment of the sepsis model.After the model and intervention were successfully prepared,the heart rate(HR),mean arterial pressure(MAP)and left ventricular systolic blood pressure(LVSP)were recorded by ECG monitoring and right common carotid artery cannulation invasive arterial moni⁃toring.Arterial blood and myocardial tissue samples were collected to detect the levels of CK⁃MB iso⁃enzyme,SOD,ROS,and copper ions.The levels of TNF⁃α,IL⁃6,NF⁃κB,and FDX1 in myocardi⁃al tissue were detected by enzyme⁃linked immunosorbent assay(ELISA).The pathological changes of myocardial tissue were detected by hematoxylin⁃eosin(HE)staining.Results:When compared with the sham⁃operated group,the levels of HR,MAP and LVSP in the septic cardiomyopathy group were decreased(P<0.05),the level of SOD was decreased(P<0.05),the levels of CK⁃MB isoen⁃zyme,ROS,copper ion,TNF⁃α,IL⁃6,NF⁃κB,and FDX1 were increased(P<0.05),the myocar⁃dial tissue of the rats in the septic cardiomyopathy group was obviously disordered,myocardial cells were swollen or broken,and a large number of inflammatory cells were infiltrated.When compared with the septic cardiomyopathy group,the HR,MAP and LVSP levels of the SAC+septic cardiomy⁃opathy group were increased(P<0.05),and the SOD level was increased(P<0.05).When com⁃pared with the septic cardiomyopathy group,the levels of enzymes,ROS,copper ions,TNF⁃α,IL⁃6,NF⁃κB,and FDX1 were decreased,myocardial injuries and inflammatory cell infiltration were less in SAC+septic cardiomyopathy group(P<0.05).Conclusion::SAC can effectively alleviate myocar⁃dial injury in rats with sepsis,and the mechanism is related to the inhibitory effect of SAC on cupro⁃ptosis in myocardial tissue.