β_3肾上腺素能受体通过微小RNA对慢性心力衰竭大鼠左心房肌L型钙离子通道的调控  

β_3 adrenergic receptor regulates left atrial L-type calcium channel in chronic heart failure rats via miRNA

作　　者：赵强[1] 邹月柳 邹筱冬 邓春玉[2] 李彪[1] 曾芳[1] Zhao Qiang;Zou Yueliu;Zou Xiaodong;Deng Chunyu;Li Biao;Zeng Fang(Department of Cardiology,Affiliated Guangzhou Red Cross Hospital of Jinan University Medical School,Guangzhou 510220,Guangdong Province,China)

机构地区：[1]暨南大学医学院附属广州红十字会医院心血管内科,510220 [2]广东省人民医院医学研究中心

出　　处：《中华老年心脑血管病杂志》2019年第1期67-71,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：广东省自然科学基金(2015A030313734);广东省科技计划(2014A020212005);广州市医药卫生科技项目(20151A011020)

摘　　要：目的探讨β_3肾上腺素能受体(β_3-AR)对慢性心力衰竭(CHF)大鼠左心房肌L型Ca2+通道亚单位α2δ-2编码基因CACNA2D2的调控是否与微小RNA(miRNA)-1及miRNA-328存在关联。方法 22只雄性Wistar大鼠随机选6只为正常对照组(NC组),另16只采用皮下注射异丙肾上腺素建立CHF动物模型,将存活的12只大鼠再随机分为CHF组6只和BRL组(在大鼠尾静脉注射β_3-AR特异性激动剂BRL-37344) 6只。采用超声心动图检测大鼠左心房内径(LAD)、左心房射血分数(LAEF)及LVEF。采用苏木精-伊红染色检测大鼠左心房肌病理学变化。采用实时荧光定量PCR检测大鼠左心房肌β_3-AR、CACNA2D2以及miRNA-1、miRNA-328表达水平。结果BRL组大鼠LAD显著大于NC组和CHF组[(4. 42±0. 15) mm vs (3. 50±0. 21) mm和(4. 09±0. 17) mm,P <0. 01]; BRL组LAEF显著低于NC组和CHF组[(34. 91±1. 51)%vs (59. 89±3. 17)%和(40. 09±0. 95)%,P <0.01]。与CHF组比较,BRL组大鼠左心房肌细胞水肿进一步加重,可见明显肥大细胞等病理学改变更显著。与NC组比较,CHF组大鼠左心房肌β3-AR、CACNA2D2、miRNA-1及miRNA-328表达上调(P <0. 01);与CHF组比较,BRL组大鼠左心房肌β3-AR、CACNA2D2、miRNA-1及miRNA-328表达进一步上调(P <0. 01)。miRNA-1、miRNA-328、CACNA2D2与β3-AR表达呈正相关(r=0. 870、0. 904、0. 911,P <0. 01); CACNA2D2与miRNA-1、miRNA-328表达呈正相关(r=0. 880、0. 954,P <0. 01)。结论β3-AR对左心房CACNA2D2的正性调控可能与miRNA-1、miRNA-328存在关联。Objective To study whether the regulatory effect ofβ3-adrenergic receptor(β3-AR)on left atrial L-type calcium channel is related with miRNA-1 and miRNA-328 in chronic heart failure(CHF)rats.Methods Twenty-two male Wistar rats were divided into control group(n=6)and model group(n=16).A CHF model of rats was established by subcutaneous injection with isoprenaline.The surviving rats in model group were further divided into CHF group(n=6)and BRL group(n=6).The LAD,LAEF and LVEF were measured by echocardiography.The pathological changes of left atrium were detected with HE staining.The expressions ofβ3-AR,CACNA2D2,miRNA-1 and miRNA-328 in left atrium were detected by RT-qPCR.Results The LAD was significantly longer while the LAEF was significantly lower in BRL group than in control group and CHF group(4.42±0.15 mm vs 3.50±0.21 mm and 4.09±0.17 mm,P<0.01;34.91%±1.51%vs 59.89%±3.17%and 40.09%±0.95%,P<0.01).The pathological changes of left atrium were more significant in BRL group than in CHF group and the expression levels ofβ3-AR,CACNA2D2,miRNA-1 and miRNA-328 were significantly higher in CHF group and BRL group than in control group and in BRL group than in CHF group(P<0.01).The expression levels of miRNA-1,miRNA-328,CACNA2D2 were positively related with those ofβ3-AR while the expression levels of CACNA2D2 were positively related with those of miRNA-1 and miRNA-328(r=0.870、0.904、0.911,P<0.01;r=0.880、0.954,P<0.01).Conclusion The regulatory effect ofβ3-AR on expression of CACNA2D2 in left atrium is related with the expressions of miRNA-1 and miRNA-328.

关 键 词：受体 肾上腺素能β3 心力衰竭 钙通道 L型 心房 微RNAS 

分 类 号：R541.6[医药卫生—心血管疾病]