多巴胺1类受体活化减轻心力衰竭早期炎症反应的实验研究  

D1-like dopamine receptor 1 activation alleviates cardiac inflammation during early stage of heart failure

作　　者：武栗妃 马友才[2] 王霞[3] 阚晓玉[4] WU Lifei;MA Youcai;WANG Xia;KAN Xiaoyu(Department of Pathophysiology,Shanxi Medical University,Taiyuan 030001,China;Department of Emergency,Beijing Anzhen Hospital,Capital Medical University;Department of Pathophysiology,Capital Medical University;Department of Hematology,Beijing Anzhen Hospital,Capital Medical University)

机构地区：[1]山西医科大学病理生理教研室,太原030001 [2]首都医科大学附属北京安贞医院急诊科 [3]首都医科大学病理生理教研室 [4]首都医科大学附属北京安贞医院血液科

出　　处：《山西医科大学学报》2021年第9期1128-1134,共7页Journal of Shanxi Medical University

摘　　要：目的探讨多巴胺1类受体的激动剂非诺多泮对心力衰竭早期炎症反应的作用。方法8周龄雄性C57BL/6J小鼠20只,随机分为两组:假手术组和TAC组,每组10只,分别喂养6周。8周龄雄性C57BL/6J小鼠40只,完全随机分为4组:假手术联合磷酸盐缓冲溶液(PBS)组、假手术联合非诺多泮组、横向主动脉弓缩窄术(TAC)联合PBS组和TAC联合非诺多泮组,每组10只。各组于手术后立即腹腔注射10 mg/kg PBS或非诺多泮,1次/d,连续注射1周。第7天时超声检查主动脉弓血流峰值和心功能,即刻处死小鼠后取心脏组织进行实时荧光定量和病理检测。提取心力衰竭小鼠心脏组织mRNA,采用实时荧光定量的方法检测多巴胺受体1-5的mRNA水平、心脏炎症因子白细胞介素1β(IL-1β)及肿瘤坏死因子-α(TNF-α)的mRNA水平。收集心力衰竭小鼠的心脏组织,免疫组化染色检查多巴胺受体的表达,伊红-苏木素染色观察心脏炎症细胞浸润。结果多普勒超声显示TAC术后1周主动脉弓血流峰值达2000 mm/s以上,假手术组小鼠主动脉弓血流峰值为800 mm/s。与假手术组比较,TAC组心脏多巴胺受体5 mRNA水平明显升高(0.21±0.02 vs 0.73±0.12,P<0.05)。与假手术组比较,TAC组免疫组化发现心脏多巴胺受体5水平增高。与假手术联合PBS组比较,TAC联合PBS组术后1周心脏炎症因子IL-1β和TNF-α的mRNA水平明显升高(4.18±0.31 vs 10.14±0.99,P<0.05;3.79±0.08 vs 14.43±2.35,P<0.05)。与TAC联合PBS组比较,TAC联合非诺多泮组术后1周心脏炎症因子IL-1β和TNF-α的mRNA水平降低(10.14±0.99 vs 4.19±0.47,P<0.05;14.43±2.35 vs 4.36±0.72,P<0.05)。与假手术联合PBS组比较,TAC联合PBS组术后1周心脏浸润的炎症细胞明显增多。与TAC联合PBS组比较,TAC联合非诺多泮组术后心脏的炎症细胞浸润减少。与TAC联合PBS组比较,TAC联合非诺多泮组术后1周射血分数和短轴缩短分数无明显变化,射血分数分别为(67.3±0.6)%和(62.8±5.Objective To investigate the effect of D1-like dopamine receptor agonist fenoldopam on cardiac inflammation during early stage of heart failure.Methods Twenty male 8-week-old C57BL/6J mice were randomly divided into two groups:sham operation group and TAC group,and the mice were sacrifaced at week 6.Forty 8-week-old male C57BL/6J mice were randomly divided into four groups(n=10 in each group):sham operation+phosphate buffered saline(PBS)group,sham operation+fenoldopam group,transverse aortic constriction(TAC)+PBS group,TAC+fenoldopam group.The mice were intraperitoneally injected with 10 mg/kg PBS or fenoldopam immediately after surgery once a day for one week in four groups,respectively.On the 7th day,ultrasound was used to analyze blood flow peak velocity and cardiac function.The mRNA levels of dopamine receptor 1-5 in heart were detected in heart failure mice using real-time fluorescent quantitative polymease chain reaction(qRT-PCR).The change of dopamine receptor 5 in heart was observed in heart failure mice by immunohistochemical staining.Mice were executed and processed for morphological and mRNA anlysis.Then henhematoxylin-eosin(HE)staining was used to observe the inflmmatory cell infiltration.QRT-PCR was used to measure the mRNA levels of inflammatory factors IL-1β,TNF-α.Results Ultrasound results showed that blood flow peak velocity at ligation achieved 2000 mm/s at week 1 after TAC in TAC group,while the blood flow peak velocity at ligation only achieved 800 mm/s in sham operation group.Compared to sham operation group,the mRNA level of dopamine receptor 5 was elevated in heart in TAC group(0.21±0.02 vs 0.73±0.12,P<0.05),and immunohistochemical staining showed that dopamine receptor 5 was also increased in heart in TAC group.Compared with sham operation+PBS group,the infiltration of inflammtory cells in heart was increased at week 1 in TAC+PBS group.Compared with TAC+PBS group,the infiltration of inflammtory cells was significantly decreased in heart in TAC+fenoldopam group.Compared with sham operat

关 键 词：多巴胺1类受体 心力衰竭 炎症反应 非诺多泮 横向主动脉弓缩窄术 

分 类 号：R541.6[医药卫生—心血管疾病]