七氟醚预处理对LPS诱导的小鼠心功能障碍的影响

摘要

AIM: To invesligale the effecls of sevoflurane (Sevo) preconditioning on myocardial dysfunclion in lipopolysaccharide (LPS) —challenged mice. METHODS; Forty male BALB/c mice were randomly allocated Lo 4 groups; conlrol group, LPS group, Sevo + LPS group and Sevo group. Following prelrealmenl wilh or wilhoul 2% Sevo for 30 min and washing out for 10 min, all mice received inlraperiloneal injeclion of LPS or normal saline ( NS). The mice received an echocardiographic evaluation by a high — resolution in vivo imaging syslem 12 h after administration of LPS or NS. The mice were then killed and the hearts were removed for histological analysis. Serum levels of lactic dehydrogenase (LDH) , crea-tine kinase — MB ( CK — MB) were measured with an automatic biochemical analyzer. The myocardium was homogenized for detecting the activity of inducible nitric oxide synthase (iNOS) and the content of nitric oxide (NO). RESULTS; Echocardiographic evaluation demonstrated that LPS resulted in an increase in tert ventricular end — diastolic volume and significant decreases in stroke volume, cardiac output and ejection fraction. The alteration of cardiac functions was inhibited by the pretreatment with Sevo. LPS caused significant elevation of LDH and CK — MB in serum samples and severe pathological damage of the hearts. Compared with LPS group, serum levels of LDH and CK — MB were reduced and pathological damage was attenuated in Sevo + LPS group. Sevo preconditioning also significantly attenuated the increases in iNOS and NO induced by LPS. CONCLUSION: Sevo preconditioning protects against myocardial impairment and myocardial dys-funclion in LPS — challenged mice. Inhibition of iNOS activity and of NO production by Sevo preconditioning may contribute to the beneficial role in the process of cardioprotection during endotoxemia.%目的:观察七氟醚(Sevo)预处理对脂多糖(LPS)诱导的心功能障碍的影响并初步探讨其作用机制.方法:40只雄性BALB/c小鼠随机分为4组:对照组(control)、LPS组、Sevo组和Sevo+LPS组.分别用2% Sevo(以纯氧为载气)或纯氧预处理30 min,洗脱10 min后,腹腔注射LPS 18 mg/kg或等量生理盐水.于腹腔注射后12 h,通过高分辨小动物超声系统检测心功能,结束后立即采血并处死小鼠,用生化分析仪检测血清乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)活性;留取小鼠心脏标本,制备石蜡切片,进行HE染色后在光学显微镜上观察各组小鼠心脏的组织结构变化,分别用硝酸还原酶法和比色法检测小鼠心肌组织中一氧化氮(NO)的含量和诱导型一氧化氮合酶(iNOS)的活性.结果:LPS 腹腔注射后12 h,超声检测显示LPS组小鼠左心室舒张末期容积(LVEDV)增大(P＜0.05),每搏输出量(SV)、心输出量(CO)和射血分数(EF)降低(P＜0.05);血清LDH和CK-MB水平升高(P＜0.05);病理切片见心肌明显病变.Sevo+LPS组与LPS组比较,LVEDV减小(P＜0.05),SV、CO和EF增加(P＜0.05),LDH和CK-MB水平显著降低(P＜0.05),心肌组织的病理损伤减轻.LPS引起心肌组织中NO含量和iNOS活性升高(P＜0.05),Sevo对此有抑制作用(P＜0.05).结论:Sevo预处理减轻LPS引起的心肌损伤和心功能障碍,其机制可能与其抑制心肌iNOS活性,减少NO的生成有关.