SR 59230A对心衰大鼠心脏MicroRNAs表达的影响

doi:10.12047/j.cjap.5561.2017.109

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (5): 456-460.doi: 10.12047/j.cjap.5561.2017.109

SR 59230A对心衰大鼠心脏MicroRNAs表达的影响

景佳妮, 李凡璐, 王茜, 宛欣, 赵倩倩, 崔香丽

山西医科大学生理学系, 细胞生理学山西省重点实验室, 太原 030001

收稿日期:2017-01-19 修回日期:2017-05-15 出版日期:2017-09-28 发布日期:2018-06-19
通讯作者: 崔香丽,Tel:0351-4135329;E-mail:cuixlcxl@sina.com E-mail:cuixlcxl@sina.com
基金资助:
崔香丽,Tel:0351-4135329;E-mail:cuixlcxl@sina.com

SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats

JING Jia-ni, LI Fan-lu, WANG Xi, WAN Xin, ZHAO Qian-qian, CUI Xiang-li

Department of Physiology, Cell Physiology Key laboratory of Shanxi Province, Shanxi Medical University, Taiyuan, Shanxi 030001, China

Received:2017-01-19 Revised:2017-05-15 Online:2017-09-28 Published:2018-06-19
Contact: 崔香丽,Tel:0351-4135329;E-mail:cuixlcxl@sina.com E-mail:cuixlcxl@sina.com
Supported by:
崔香丽,Tel:0351-4135329;E-mail:cuixlcxl@sina.com

摘要/Abstract

摘要： 目的：观察β3肾上腺素受体（β3-AR）对心衰大鼠心脏MicroRNAs表达的影响及可能的作用机制。方法：大鼠冠脉左前降支结扎造成心衰模型，假手术大鼠只穿线不结扎。造模成功大鼠再随机分为：心衰组（CHF control group）和心衰+SR 59230A组（CHF+SR group）；假手术大鼠也随机分为假手术组（Sham group）和假手术+SR 59230A组（Sham+SR group）。Sham+SR组和CHF+SR组每天两次腹腔注射SR （85 mmol/L，1 ml），连续注射7周。结果：①miScript miRNA PCR Arrays显示，在体阻断β3-AR后，假手术组与心衰组有18种MicroRNAs共同表达下调；经文献比对，与NF-κB相关的MicroRNAs有6种，分别为miR-125b-5p，miR-143-3p，miR-145-5p，miR-26a-5p，miR-30a-5p和miR-320-5p。②大鼠心脏组织切片观察到NF-κB在心衰大鼠心肌细胞核与细胞质中均有分布，而p53在心肌细胞质分布较多，NF-κB和p53表达明显高于假手术组（P<0.05）。阻断β3-AR后，心衰组心脏NF-κB和p53表达显著减少（P<0.05），而假手术组NF-κB和p53表达略增加（P<0.05）。③Western blot结果发现心衰大鼠NF-κB p65表达高于假手术组（P<0.05），给予β3-AR阻断剂后，心衰组心脏NF-κB p65和p53-Phospho-Serine 15表达均下降（P<0.05），而假手术组心脏阻断β3-AR后，NF-κB、p53和p53-Phospho-Serine 15表达均增加（P<0.05）。结论：阻断β3肾上腺素受体有利于缓解心衰大鼠心脏的损伤；β3-AR可引起MicroRNAs表达变化且与NF-κB信号通路有关。

关键词: 大鼠, 心脏, β3肾上腺素受体, SR 59230A, MicroRNAs, NF-κB

Abstract: Objective: To investigate the effects of β3-adrenoceptors(β3-AR) inhibitor SR 59230A on MicroRNAs expression in rat myocardium with chronic heart failure and the related mechanisms.Methods: One hundred male SD rats were randomly divided into sham operated group(40)and chronic heart failure(CHF)group(60). Coronary artery ligation was used to induce CHF. Then the rats in CHF group were further randomly divided into CHF control group and CHF+SR 59230A group (CHF+SR). Rats in the sham group were divided into sham control group and sham+SR 59230A group (Sham+SR). The rats in Sham+SR group and CHF+SR group were treated with 1 ml SR 59230A(85 mmoL/L in 0.9% saline)twice a day for seven weeks by intraperitoneal injection, while the rats in control groups were injected with the same amount of saline for seven weeks separately. miScript miRNA PCR Arrays were used to determine the expression profile of MicroRNAs. Immunohistochemistry was used to evaluate the distribution of the related proteins in the heart tissue sections. Western blot was used to detect the expressions of nuclear factor-kappaB(NF-κB),p53 and p53-Phospho-Serine 15 in the heart.Results: ①After in vivo blockade of β3-AR by SR 59230A, there were 18MicroRNAs down-regulated in sham control group and CHF control group. Within them, 6 MicroRNAs were related to NF-κB signaling pathway, they were miR-125b-5p,miR-143-3p,miR-145-5p,miR-26a-5p,miR-30a-5p and miR-320-5p. ②Slides from the heart tissue showed that NF-κB was distributed both in nucleus and cytoplasm, while p53 in cytoplasm was more than that in nucleus in heart tissue sections. The expressions of NF-κB and p53 were higher in the CHF control group than those in the sham control group(P<0.05), but were lower in CHF+SR group than those in CHF control group(P<0.05),while they were elevated in Sham+SR group compared to the sham control group(P<0.05). ③ Compared with the sham control group, the protein expression of NF-κB p65 was increased significantly in the CHF control group (P<0.05). After treated with SR59230A in vivo,the protein expressions of NF-κB and p53-Phospho-Serine 15 were decreased significantly in CHF rats(P<0.05),while the protein expressions of NF-κB, p53 and p53-Phospho-Serine 15 proteins were increased in the sham rats (P<0.05).Conclusion: Blocking of β3-AR improved the damaged heart in CHF rats; β3-AR caused the change of MicroRNAs expression, and it related to NF-κB signal pathway.

Key words: rats, hearts, β3-adrenoceptors, SR 59230A, MicroRNAs, NF-κB

景佳妮, 李凡璐, 王茜, 宛欣, 赵倩倩, 崔香丽. SR 59230A对心衰大鼠心脏MicroRNAs表达的影响[J]. 中国应用生理学杂志, 2017, 33(5): 456-460.

JING Jia-ni, LI Fan-lu, WANG Xi, WAN Xin, ZHAO Qian-qian, CUI Xiang-li. SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats[J]. CJAP, 2017, 33(5): 456-460.

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SR 59230A对心衰大鼠心脏MicroRNAs表达的影响

SR 59230A on the expression of MicroRNAs in myocardium of heart failure rats

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