摘要
目的:观察他克莫司通过激活酪氨酸激酶(JAKs)/信号转导因子和转录激活因子(STATs)信号通路对川崎病小鼠血管内皮功能及心肌细胞凋亡的影响。方法:选取健康级小鼠40只,适应性喂养1周后分为正常组、模型组、阿司匹林组、他克莫司组,每组10只小鼠。除正常组10只小鼠外,其余30只小鼠均建立川崎病模型。建模成功后,正常组和模型组分别采用相应体积的0.5%羧甲基纤维素钠水溶液灌胃,阿司匹林组采用阿司匹林50 mg/kg灌胃,他克莫司组采用他克莫司40 mg/kg灌胃。应用超声心动图测定小鼠心脏功能,采用酶联免疫吸附法(ELISA)检测川崎病小鼠血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、血管内皮生长因子(VEGF)表达,采用苏木精-伊红(HE)染色观察各组小鼠病理组织,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(TUNEL)检测小鼠心肌细胞凋亡率,蛋白免疫印迹法(Western Blot)检测JAK2、STAT3蛋白表达。结果:正常组小鼠心脏舒张功能正常、无障碍产生;模型组小鼠出现心脏舒张功能障碍,左室舒张末期内径(LVEDD)增加,左室射血分数(LVEF)降低;他克莫司组LVEF有所提升,LVEDD相对减少;阿司匹林组心脏舒张功能略微缓解,LVEF、LVEDD等略显改善。与正常组比较,模型组TNF-α、IL-6、VEGF表达升高(P<0.05);与模型组比较,他克莫司组TNF-α、IL-6、VEGF表达降低(P<0.05);与他克莫司组比较,阿司匹林组TNF-α、IL-6、VEGF表达升高(P<0.05)。正常组小鼠心肌纤维排列整齐,细胞排列有序紧密,细胞核呈卵圆形,细胞质鲜红;模型组小鼠心肌纤维排列紊乱且心肌组织断裂和溶解,间质纤维化和组织坏死,细胞排列紊乱,出现水肿和坏死等,细胞核大小不均匀并有炎性浸润;他克莫司组心肌断裂组织及溶解现象有所缓解,细胞核排列趋于整齐,分布趋于有序、紧密;阿司匹林组心肌纤维排列紊乱现象有所缓解,部分�
Objective:To observe the effects of tacrolimus on vascular endothelial function and cardiomyocyte apoptosis in mice with Kawasaki disease by activating tyrosine kinase(JAKs)/signal transduction factor and transcriptional activator(STATs)signaling pathway.Methods:After 1 week of adaptive feeding,forty healthy mice were selected and divided into normal group,model group,aspirin group,and tacrolimus group,with 10 mice in each group.Kawasaki disease model was established in 30 mice except 10 mice in normal group.After modeling,the normal group and the model group were gavaged with the corresponding volume of 0.5%aqueous solution of sodium methylcellulose,the aspirin group was gavaged with aspirin 50 mg/kg,and the tacrolimus group was gavaged with tacrolimus 40 mg/kg.The cardiac function of mice was detected by echocardiography,the expressions of interleukin-6(IL-6),tumor necrosis factorα(TNF-α)and vascular endothelial growth factor(VEGF)in mice with Kawasaki disease were detected by enzyme-related immunosorbent assay(ELISA),and the pathological changes of tissues in each group were observed by hematoxylin-eosin(HE)staining.The rate of cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay(TUNEL),and the expressions of JAK2 and STAT3 were detected by Western Blot.Results:Cardiac diastolic function in the normal group was normal.Cardiac diastolic function in the model group was observed,left ventricular end-diastolic diameter(LVEDD)was increased,and left ventricular ejection fraction(LVEF)was decreased.LVEF in the tacrolimus group was increased,LVEDD was decreased.Cardiac diastolic function in the aspirin group was slightly relieved,and LVEF and LVEDD were slightly improved.Compared with normal group,the expressions of TNF-α,IL-6,and VEGF in the model group were increased(P<0.05).Compared with model group,the expressions of TNF-α,IL-6,and VEGF in the tacrolimus group were decreased(P<0.05).Compared with tacrolimus group,the expressions of TNF-α,IL-6 and
作者
娄萍
赵欣
赵颖
张丹
LOU Ping;ZHAO Xin;ZHAO Ying;ZHANG Dan(Shaanxi Provincial People's Hospital,Xi'an 710068,Shaanxi,China)
出处
《中西医结合心脑血管病杂志》
2023年第12期2170-2175,共6页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
陕西省国际科技合作计划项目(No.S2021-YF-GHMS-0100)。
关键词
川崎病
他克莫司
酪氨酸激酶/信号转导因子和转录激活因子信号通路
血管内皮
心肌细胞
凋亡
小鼠
实验研究
Kawasaki disease
tacrolimus
activating tyrosine kinase/signal transduction factor and transcriptional activator signaling pathway
vascular endothelium
cardiomyocytes
apoptosis
mice
experimental study
