Lin Jing, Zhou Li-hua, Chen Xin, Huang Zhi-min
Intensive Care Unit, Affiliated Hospital of Inner Mongolia Medical College, Huhehot 010050, Neimenggu, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012 Apr;24(4):207-10.
To investigate the pathogenesis of stress myocardial injury.
Thirty Wistar rats were randomly divided into three groups, with 10 rats in each group: normal control group, movement restriction and ice swimming stress group (rat movement was restricted 6 hours per day; beginning from 13th day rats were allowed to swim in ice water for 5 minutes, ice stress group), and endotoxin stress group [intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg, LPS group]. The myocardial tissue was harvested, the pathological changes in myocardial was observed with light microscopy, and the changes in myocardial ultrastructure were observed with electron microscope. The levels of serum cardiac troponin I (cTnI) was determined by enzyme-linked immunosorbent assay (ELISA), apoptosis of myocardial cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the apoptotic index was calculated.The caspase-8 and caspase-3 expression in myocardial tissue were assessed by immunohistochemistry. The correlation between caspase and apoptotic index was analyzed.
Compared with normal control group, in ice stress group and LPS group, myocardial tissue was found to be injured seriously in different degrees under light microscopy and electron microscopy; the content of cTnI (μg/L) in serum was significantly increased (0.63 ± 0.12, 0.74 ± 0.08 vs. 0.53 ± 0.03, P < 0.05 and P < 0.01); apoptosis index of myocardial tissue was significantly increased in different degrees [(7.91 ± 1.71)%, (12.94 ± 2.00)% vs. 0]; caspase-8 and caspase-3 expressions in the myocardium were increased (caspase-8 gray scale: 126.65 ± 3.13, 114.82 ± 8.67 vs. 156.99 ± 9.66; caspase-3 gray scale: 130.20 ± 2.96, 108.58 ± 5.72 vs. 160.51 ± 5.25, all P < 0.01). However, the above indexes in LPS group were significantly higher than those in ice stress group (P < 0.05 or P < 0.01). The correlation analysis showed that in ice stress group, positive correlation was found between caspase-8, caspase-3 and apoptotic index [r(1) = 0.914, P(1) = 0.002; r(2) = 0.929, P(2) = 0.001]; in LPS group, the positive correlation also exist between caspase-8, caspase-3 and apoptotic index [r(1) = 0.956, P(1) = 0.000; r(2) = 0.916, P(2) = 0.001].
Severe stress may produce stress injury of myocardium via increasing expression of caspase-8 and caspase-3 protein.
探讨应激性心肌损伤的发病机制。
将30只Wistar大鼠随机分为3组，每组10只：正常对照组、运动限制及冰水游泳应激组（大鼠每天运动限制6小时；从第13天起大鼠每天在冰水中游泳5分钟，即冰应激组）和内毒素应激组[腹腔注射脂多糖（LPS）10mg/kg，即LPS组]。取心肌组织，光镜下观察心肌病理变化，电镜下观察心肌超微结构变化。采用酶联免疫吸附测定（ELISA）法测定血清心肌肌钙蛋白I（cTnI）水平，采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测心肌细胞凋亡，并计算凋亡指数。采用免疫组织化学法检测心肌组织中半胱天冬酶-8（caspase-8）和半胱天冬酶-3（caspase-3）的表达。分析半胱天冬酶与凋亡指数的相关性。
与正常对照组比较，冰应激组和LPS组光镜及电镜下均可见不同程度的心肌组织损伤；血清cTnI含量（μg/L）显著升高（0.63±0.12，0.74±0.08比0.53±0.03，P<0.05和P<0.01）；心肌组织凋亡指数不同程度显著升高[（7.91±1.71）%，（12.94±2.00）%比0]；心肌中caspase-8和caspase-3表达增加（caspase-8灰度值：126.65±3.13，114.82±8.67比156.99±9.66；caspase-3灰度值：130.20±2.96，108.58±5.72比160.51±5.25，均P<0.01）。但LPS组上述指标均显著高于冰应激组（P<0.05或P<0.01）。相关性分析显示，冰应激组caspase-8、caspase-3与凋亡指数呈正相关[r（1）=0.914，P（1）=0.002；r（2）=0.929，P（2）=0.001]；LPS组caspase-8、caspase-3与凋亡指数也呈正相关[r（1）=0.956，P（1）=0.000；r（2）=0.916，P（2）=0.001]。
严重应激可能通过增加caspase-8和caspase-3蛋白表达而产生心肌应激性损伤。
