南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (05): 624-631.doi: 10.12122/j.issn.1673-4254.2020.05.03

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从CXCL12/CXCR4轴探析空瓶诱导的慢性情绪应激对急性心肌梗死大鼠炎性因子的影响

侯季秋，陈雅丽，马 迪，王 超，靳会会，安 莹，赵海滨   

  • 出版日期:2020-05-20 发布日期:2020-05-20
  • 基金资助:

Effect of chronic emotional stress induced by empty bottle stimulation on inflammatory factors in rats with acute myocardial infarction: analysis of the CXCL12/CXCR4 axis

  

  • Online:2020-05-20 Published:2020-05-20

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摘要： 目的 探析空瓶刺激诱导的慢性情绪刺激对急性心梗大鼠CXCL12/CXCR4介导的炎性反应影响。方法 采用21 d不确定空瓶饮水刺激法建立焦虑模型，冠状动脉左前降支结扎方法建立心肌梗死模型，于焦虑造模的第15天进行心梗手术造模建立 复合模型。随机分为假手术组（只穿线不结扎，n=6）、心肌梗死组（结扎冠脉左前降支，n=6）、复合模型组（结扎冠脉左前降支结合不确定空瓶饮水刺激，n=6），抑制剂组（复合模型组基础上经腹腔注射AMD3100（1 mg·kg-1·d-1），给药6 d，n=7）。超声心动检测左室射血分数（LVEF）、左心室缩短分数（LVFS）等评价大鼠心脏功能，高架迷宫试验、旷场试验评价大鼠行为学， ELISA、免疫组化检测CXCL12、CXCR4、IL-1β、IL-18、NE的表达情况。结果 复合模型组大鼠LVEF、LVFS均低于假手术组及心梗组（P<0.05），抑制剂组LVEF、LVFS均高于复合模型组（P<0.05），抑制剂组LVID;d、LVID;s均低于复合模型组（P<0.05）；高架十字迷宫试验中复合模型组大鼠停留在开臂时间及进入开臂的次数均明显低于假手术组及心梗组（P<0.05），抑制剂组大鼠在开臂上的时间及进入开臂的次数比复合模型组明显增加（P<0.05），旷场试验中复合模型组大鼠的水平运动和垂直运动较假手术组与心梗组减少（P<0.05），而抑制剂组大鼠垂直运动较复合模型组增加（P<0.05）；复合模型组大鼠心梗边缘区CXCR4表达均高于假手术组、心梗组和抑制剂组（P<0.05）；抑制剂组IL-1β、IL-18、中性粒细胞活性蛋白酶的表达均低于复合模型组（P<0.05）；与假手术组相比，复合模型组尼氏体的数量明显减少（P<0.01）。结论 空瓶刺激诱导的慢性情绪应激可导致CXCL12/CXCR4轴功能失调，造成心梗后炎性级联反应，恶化心梗后心肌细胞坏死、心功能及海马神经元的损伤。

Abstract: Objective To investigate the effect of chronic emotional stimulation induced by empty bottle stimulation on CXCL12/ CXCR4-mediated inflammatory response in rats with acute myocardial infarction (AMI). Methods Rat models of anxiety were established by a 21-day stimulation with uncertain empty bottle drinking water, and myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery; compound models were established by performing myocardial infarction operation on the 15th day of anxiety modeling. The rats were randomly divided into 4 groups: shamoperated group (n=6), myocardial infarction group (n=6), compound model group (with myocardial infarcted and anxiety; n= 6), and inhibitor group (compound models treated daily with 1 mg/kg AMD3100 for 6 days; n=7). Echocardiography was used to examine the LVEF and LVFS to evaluate the cardiac function of the rats. Elevated maze test and open field test were used to evaluate the behaviors of the rats. The expressions of CXCL12, CXCR4, IL-1β, IL-18 and neutrophil active protease (NE) in the myocardial tissues and blood samples were detected with ELISA and immunohistochemistry. Results The LVEF and LVFS were lower in the compound model group than in the sham group and myocardial infarction group (P<0.05), and were higher in inhibitor group than in the compound model group (P<0.05). LVID;d and LVID;s were lower in the inhibitor group than in the compound model group (P<0.05). Compared to those in the sham group and myocardial infarction group, the rats in the compound model group more obviously preferred to stay in the closed arm (P<0.05) in EPM; the rats in the inhibitor group had more times of entering and staying in the open arm than the compound model rats (P<0.05); the horizontal and vertical movements were less in the compound model rats than in those in the sham group and the myocardial infarction group (P<0.05) in OFT, and the vertical movement of the rats in inhibitor group was higher than those in the compound model group (P< 0.05). The expression of CXCR4 in the marginal zone of myocardial infarction was significantly higher in the compound model group than in the sham-operated group, myocardial infarction group and inhibitor group (P<0.05). The expressions of IL-1β, IL-18 and NE in the inhibitor group were significantly lower than those in the compound model group (P<0.05). Compared with at in the sham-operated group, the number of Nissl bodies in the compound model group decreased significantly (P< 0.01). Conclusion Chronic emotional stress induced by empty bottle stimulation can lead to dysfunction of the CXCL12/CXCR4 axis, which causes inflammatory cascade after myocardial infarction to worsen myocardial cell necrosis, cardiac function and hippocampal neuronal damage after the infarction.