摘要
目的:观察右美托咪定对左向右分流型先天性心脏病大鼠心脏功能及认知功能的影响。方法:30只6周龄SPF级大鼠,按随机数字表法分为正常对照组(n=6)、模型组(n=12)和模型干预组(n=12);后两组行套管法右颈总动脉-颈外静脉分流术建立左向右分流型先天性心脏病模型。模型干预组大鼠术前腹腔注射右美托咪定(100mg/kg)1次,术后每3天1次,共6周;模型组和正常对照组同法注射等量生理盐水。术后每周监测各组大鼠体重;第2、4、6周采用水迷宫试验观察各组大鼠逃避潜伏时间,检测各组大鼠认知功能;术后6周末采用小动物超声成像系统检测各组大鼠心功能指标:右室舒张末期前后径(RVEDD)、右室前壁舒张末期厚度(RVWTd)、室间隔舒张末期厚度(IVSd),之后断头处死各组大鼠,采用ELISA检测各组大鼠血清炎性因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和血清心肌细胞损伤标记物氨基端前B型钠尿肽(NT-proBNP)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白(cTnI);摘取大脑和心脏进行组织HE染色和Masson染色观察海马组织损伤及右心室心肌纤维化;同时Western blotting检测海马和心脏组织IL-6、IL-1β、TNF-α水平。结果:6周末模型组大鼠体重显著低于正常对照组,模型干预组明显高于模型组(均P<0.01)。相比于正常对照组,模型组大鼠术后第2、4、6周的逃避潜伏时间显著延长,模型干预组较模型组明显缩短(均P<0.05)。术后6周末,模型组心功能指标RVEDD、RVWTd、IVSd水平较正常对照组明显升高,而模型干预组较模型组明显降低(均P<0.01);心肌损伤标志物NT-proBNP、CK-MB、cTnI模型组显著高于正常对照组,模型干预组明显低于模型组(均P<0.01);HE染色和Masson染色显示,模型组大鼠呈现明显海马组织损伤及右心室心肌纤维化,而模型干预组得到明显改善。血清、海马及心肌组织炎性因子IL-6、IL-1β、TNF-α水平,模型组显著高于正常对照组,模型干预组较模型组明显降低(均P<0.05)。结论:右美托咪定能够显著改善左向右分流型先天性心脏病大鼠心脏功能及认知功能。
Objective:To investigate the effects of dexmedetomidine on the cardiac function and cognitive function of left to right shred congenital heart disease in rats.Method:Thirty 6-week-old SPF rats were divided into normal control group(n=6),model group(n=12)and model intervention group(n=12)according to random number table method;The left-to-right shunt type congenital heart disease model was established by common carotid artery-external jugular vein shunt.Rats in model intervention group were intraperitoneally injected with dexmedetomidine(100mg/kg)once before operation,and once every 3 days after operation for 6 weeks;model group and normal control group were injected with the same amount of normal saline in the same way.The body weight of the rats in each group was monitored every week after the operation;the water maze test was used to observe the escape latency of the rats in each group at the 2nd,4th and 6th week,and the cognitive function of the rats in each group was detected;Six weeks after the operation,the small animal ultrasound imaging system was used to detect the cardiac function indexes of right ventricular end-diastolic diameter(RVEDD),right ventricular anterior wall end-diastolic thickness(RVWTd)and ventricular septal end-diastolic thickness(IVSd)in each group.Rats in each group were sacrificed,and serum inflammatory factors interleukin 6(IL-6),interleukin 1b(IL-1β),tumor necrosis factorα(TNF-α)and serum myocardial cell damage markers amino-terminal pro-B-type natriuretic peptide(NT-proBNP),creatine kinase isoenzyme(CK-MB),cardiac troponin(cTnI);brains and hearts were harvested for tissue HE staining and Masson staining to observe the damage of hippocampus and myocardial fibrosis of right ventricle;At the same time,Western blotting was used to detect the levels of IL-6,IL-1βand TNF-αin hippocampus and heart tissue.Results:The body weight of rats in the model group was significantly lower than that of the normal control group at the end of 6 weeks,and the model intervention group was significantly higher than the model group(both P<0.01).Compared with the normal control group,the escape latency of rats in the model group was significantly prolonged at the 2nd,4th,and 6th weeks after operation,and the model intervention group was significantly shorter than the model group(all P<0.05).At 6 weeks after operation,the levels of cardiac function indexes RVEDD,RVWTd and IVSd in the model group were significantly higher than those in the normal control group,while those in the model intervention group were significantly lower than those in the model group(all P<0.01);myocardial injury markers NT-proBNP,CK-MB and cTnI in model groups were significantly higher than the normal control group,and the model intervention group was significantly lower than the model group(both P<0.01).HE staining and Masson staining showed that the rats in the model group showed obvious hippocampal tissue damage and right ventricular myocardial fibrosis.The model intervention group showed significant improvement.The levels of serum,hippocampal/myocardium inflammatory factors IL-6,IL-1β,and TNF-αin the model group were significantly higher than the normal control group,and the model intervention group was significantly lower than the model group(all P<0.05).Conclusion:Dexmedetomidine can significantly improve the cardiac function and cognitive function in rats with left-to-right shred congenital heart disease.
作者
刘新燕
周佩佩
马漫漫
李东兴
侯俊德
韩银锋
LIU Xin-yan;ZHOU Pei-pei;MA Man-man;LI Dong-xing;HOU Jun-de;HAN Yin-feng(Department of Anesthesiology, Handan Central Hospital, Handan 056001, China)
出处
《微循环学杂志》
2022年第1期6-11,18,共7页
Chinese Journal of Microcirculation
基金
河北省科技计划项目(162777196)。
关键词
右美托咪定
左向右分流型先天性心脏病
心脏功能
认知
Dexmedetomidine
Left to right shred congenital heart disease
Cardiac function
Cognitive dysfunction
