精神分裂症大鼠心功能与血管内皮生长因子表达的关系研究

Relationship between cardiac function and the expression of vascular endothelial growth factor in schizophrenic rats

目的 探讨精神分裂症大鼠心功能变化及心功能与心肌组织血管内皮生长因子(VEGF)表达的关系。方法 SD大鼠在怀孕9 d时,对孕鼠经尾静脉分别注射聚肌胞苷酸(Poly I:C)、等体积生理盐水(模型组、对照组孕鼠各5只),制备母体免疫激活模型,检测孕鼠血清白介素-6和肿瘤坏死因子α表达,以检验母体免疫激活模型制备情况。在子鼠42 d时,从每个亲代所产生的子鼠中随机选取出1~3只,模型组、对照组子鼠各12只。待子鼠进入成年期后,进行前脉冲抑制(PPI)实验。对两组子鼠进行M型超声检查评估其心功能;对两组子鼠心脏标体进行苏木素-伊红(HE)染色观察形态学变化,采用免疫组织化学染色观察VEGF的表达。结果 模型组子鼠左心室射血分数及左心室短轴缩短率均低于对照组(P<0.01),左心室收缩末期内径、左心室舒张末期内径及每搏量均高于对照组(P<0.01)。HE染色结果显示,对照组子鼠心肌排列整齐,胞质分泌均匀,胞核清晰可见;模型组子鼠心肌排列稍紊乱,可见部分心肌受损;免疫组织化学染色结果显示,模型组子鼠左室心肌细胞中VEGF表达较多。结论 精神分裂症大鼠心功能减弱、心肌受损,VEGF表达增多。VEGF有望作为监测精神分裂症患者心肌受损的指标之一。

Objective To explore the changes of cardiac function in schizophrenic rats and the relationship between cardiac function and the expression of vascular endothelial growth factor(VEGF).Methods On the 9th day of pregnancy,pregnant schizophrenic rats were injected with polyinosinic-polycytidylic acid(Poly I:C)and equal volume normal saline(model and control group with 5 ones in each),maternal immune activation model was prepared,and serum interleukin 6(IL-6)and tumor necrosis factor-alpha(TNF-α)expression of pregnant rats were detected to test the preparation of the maternal immune activation model.On the 42th day of cubs,1~3 ones were randomly selected from each parent(model and control group with 12 in each).Prepulse inhibition(PPI)experiments were conducted after cubs entered adulthood.M-ultrasound examinations were conducted to assess cardiac functions in cubs of both groups,hematoxylin-eosin staining was performed on cubs'hearts to observe the morphological changes and the expression of VEGF protein was detected using immunohistochemical method.Results Left ventricular ejection fraction and short axis shortening rate of cubs were lower(P<0.01)and end-systolic and end-diastolic diameter of left ventricular as well as stroke volume were higher(P<0.01)in model than control group.The results of hematoxylin-eosin staining showed that myocardial alignment was neat,cytoplasm secretion uniform,and nucleus clearly visible in cubs of control group,myocardial alignment was slightly disordered and partial myocardium was damaged in cubs of model group,the results of immunohistochemical staining showed that the VEGF expression was more in left ventricular myocardial cells in cubs of model group.Conclusion Cardiac function weakens,myocardium damages,and the VEGF expression increases in schizophrenia rats.The VEGF is hopeful to be one of the indicators to monitor myocardial damage in patients with schizophrenia.