论文部分内容阅读
目的:研究安体舒通对脓毒症大鼠心肌损伤的保护作用,为脓毒症心肌损伤的诊治提供新措施。方法:120只雄性Sprague-Dawley大鼠随机(随机数字法)分为3组:假手术组、盲肠结扎穿孔(cecal ligation and perforation, CLP)组、安体舒通组。假手术组大鼠仅施行开腹暴露盲肠并还纳,CLP组和安体舒通组行脓毒症造模,结扎盲肠穿孔并挤出肠内容物后还纳腹腔缝合。安体舒通组以灌胃形式给予安体舒通[20 mg/(kg·d)],假手术组和CLP组给予同等剂量的生理盐水,观察7 d,处死大鼠后采血并取出心肌组织。采用ELISA法分别检测大鼠血清中肿瘤坏死因子-α(tumor necrosis factor-α TNF-α、白介素-6(interleukin-6, IL-6)、心肌肌钙蛋白I(cardiac troponin I, cTnI)及肌酸激酶同工酶MB(creatine kinase-MB, CK-MB)含量变化;心脏超声检测大鼠心脏结构及功能;TUNEL染色检测大鼠左心室肌细胞相对凋亡数量;免疫组织化学检测大鼠左心室TNF-α、IL-6、Bax(bcl2-associated X protein)、Bcl2 (B cell lymphoma 2)和Caspase3表达水平。结果:与CLP组大鼠相比,安体舒通组大鼠血清及心室肌组织中TNF-α和IL-6含量显著减少(n P<0.05);血清中cTnI及CK-MB含量明显降低(n P<0.05);心率(heart rate, HR)、左心室舒张内径(left ventricular diastolic dimension, LVDd)显著降低(n P<0.05),射血分数(ejection fraction, EF)、左室短轴缩短率(left ventricular fractional shortening, FS)明显增加(n P<0.05);心室肌凋亡改善(n P<0.05),凋亡相关蛋白Bcl2明显增加(n P<0.05),Bax和Caspase3表达明显下调(n P<0.05)。CLP组大鼠Bcl2蛋白表达、EF及FS较假手术组明显降低(n P<0.05),余指标显著高于假手术组(n P<0.05)。n 结论:安体舒通能够通过减轻脓毒症引起的炎症反应,减轻心肌受损,缓解心室肌凋亡,改善心室结构及功能,治疗脓毒症心肌损伤。“,”Objective:To investigate the protective effect of spironolactone on myocardial injury in septic rats and to provide a novel measure for the diagnosis and treatment of sepsis myocardial injury.Methods:Totally 120 male Sprague-Dawley rats were randomly divided into the sham group, cecal ligation and perforation group (CLP group), and spironolactone group. The sham group was only exposed to the cecum by laparotomy. CLP was performed to induce sepsis in the CLP group and spironolactone group. The cecal perforation was ligated and the contents of the intestine were squeezed out. The spironolactone group was administered spironolactone by gavage with a dose of 20 mg/(kg·d) per rat. The sham and CLP groups were given the same dose of saline. The experiment period was 7 days. After the rats were sacrificed, blood was collected and myocardial tissue was removed. The changes of serum TNF-α, IL-6, cTnI and CK-MB levels were detected by ELISA. Cardiac structure and function were detected by echocardiography. The relative apoptosis of left ventricular myocytes in rats was detected by TUNEL staining. The levels of TNF-α, IL-6, Bcl2-associated X protein (Bax), B cell lymphoma 2 (Bcl2) and Caspase 3 in the left ventricle tissue were detected by immunohistochemistry.Results:Compared with the CLP group, the levels of TNF-α and IL-6 in serum and left ventricular tissue were significantly decreased (n P<0.05) and serum levels of cTnI and CK-MB were significantly down-regulated (n P<0.05). Heart rate (HR) and left ventricular diastolic dimension (LVDd) were significantly reduced (n P<0.05), and ejection fraction (EF) and left ventricular fractional shortening (FS) increased significantly (n P<0.05). Ventricular muscle apoptosis was improved (n P<0.05),the level of apoptosis-related protein Bcl2 was increased and the Bax and Caspase3 expression were significantly down-regulated (n P<0.05).The expression of Bcl2 protein, EF and FS in the CLP group were significantly lower than those in the sham group(n P<0.05), and the remaining indexes were significantly higher than those in the sham group(n P<0.05).n Conclusions:Spironolactone can treat sepsis-induced myocardial injury by reducing inflammatory response caused by sepsis, reducing myocardial damage, alleviating ventricular muscle apoptosis, and improving ventricular structure and function.