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鲍宏刚,苏芳菊,徐志勇,朱立强,薛 丽,杨海青.κ阿片受体选择性激动剂U50488H对大鼠心房纤维化及缝隙连接蛋白43重构的影响[J].现代生物医学进展英文版,2020,(10):1824-1828.
κ阿片受体选择性激动剂U50488H对大鼠心房纤维化及缝隙连接蛋白43重构的影响
Effects of Selective κ-opioid Receptor Agonist U50488H on Atrial Fibrosis and Connexin43 Remodeling in Rats
Received:November 26, 2019  Revised:December 22, 2019
DOI:10.13241/j.cnki.pmb.2020.10.006
中文关键词: U50488H  心房纤维化  Cx43重构  κ阿片受体
英文关键词: U50488H  atrial fibrosis  Cx43  κ-opioid receptor
基金项目:全军2017年后勤科研面上项目(CWH17L004)
Author NameAffiliationE-mail
BAO Hong-gang Department of Cardiology, The central theater air force hospital, Datong, Shanxi, 037000, China baohonggang@163.com 
SU Fang-ju Department of Cardiology, 940 Hospital of PLA, Lanzhou, Ganshu, 730000, China  
XU Zhi-yong Department of Cardiology, The central theater air force hospital, Datong, Shanxi, 037000, China  
ZHU Li-qiang Department of Cardiology, The central theater air force hospital, Datong, Shanxi, 037000, China  
XUE Li Department of Cardiology, The central theater air force hospital, Datong, Shanxi, 037000, China  
YANG Hai-qing Department of Cardiology, The central theater air force hospital, Datong, Shanxi, 037000, China  
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中文摘要:
      摘要 目的:观察κ阿片受体选择性激动剂U50488H对大鼠心房纤维化及缝隙连接蛋白43重构的影响。方法:40只SPF级雄性wistar大鼠(180±20 g)随机等分为4组:对照组、盐酸异丙肾上腺素(isoprenaline ISO)[5 mg/(kg?d)](ISO组)、ISO[5 mg/(kg?d)]+U50488H [1.5 mg/(kg?d)]组(U50488H组)、ISO[5 mg/(kg?d)]+Nor-BNI(κ阿片受体阻断剂)[2 mg/(kg?d)] +U50488H [1.5 mg/(kg?d)]组(Nor-BNI组)。每组每天1次给予相应试剂, 7 d后处死大鼠。H-E染色法观察心肌纤维化情况;Masson染色法计算胶原容积分数;免疫组化SP法观察Cx43分布,并进行半定量分析;Western blot检测Cx43蛋白的表达。结果:① HE、Masson染色结果示对照组无明显心房纤维化,ISO组出现明显的纤维化,而U50488H组较ISO组心房纤维化程度均减弱(P均<0.01),其效应可被Nor-BNI抑制。② Cx43含量在ISO组较对照组均减少(P均<0.01),分布无规律性,侧面分布相对增多,U50488H组中Cx43含量减少程度较ISO组减弱(P<0.01),且分布较规律。其效应可被Nor-BNI阻断。结论:κ阿片受体选择性激动剂U50488H可抑制大鼠心房纤维化及缝隙连接蛋白43重构。
英文摘要:
      ABSTRACT Objective: To observe the effects of selective κ-opioid receptor agonist U50488H on atrial fibrosis and connexin43 remodeling in rats induced by Isoprenaline(ISO). Methods: Forty SPF male wistar rats were randomly divided into four groups(n=10): control group, ISO(5 mg/[kg?d]) group (ISO group), ISO[5 mg/(kg?d)]+U50488H [1.5 mg/(kg?d)] group (U50488H group), ISO[5 mg/(kg?d)]+Nor-BNI [2 mg/(kg?d)]+U50488H [1.5 mg/(kg?d)]group(Nor-BNI group). Each group was given corresponding reagents once a day. The rats were killed after 7 days. H-E staining was used to observe myocardial fibrosis and Masson staining was used to calculate collagen volume fraction; Immunohistochemical method was used to observe the distrubutiong of Cx43, Western blot was used to detecte the expression of Cx43. Results: ①The results of H-E and Masson staining showed that there was no significant atrial fibrosis in the control group and there was significant fibrosis in the ISO group, while the degree of atrial fibrosis in the U50488H group was weaker than that in the ISO group(P<0.01), and its effect could be inhibited by Nor BNI. ② Compared with the control group, the Content of Cx43 obviously reduced(P<0.01)and distribution disordered very much in ISO group, while the content of Cx43 in U50488H group was not obvious changed(P<0.01)and the distribution is regularly, the effect of U50488H can be inhibited by Nor-BNI. Conclusion: The selective agonist U50488H of κ opioid receptor can inhibit the atrial fibrosis and the connexin 43 remodeling in rats.
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