Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.
Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.
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DOI：
10.1371/journal.pone.0069053
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sunagawa K
中科院分区：
文献类型：
--
作者：
Ogawa K;Hirooka Y;Kishi T;Ide T;Sunagawa K
左室重构和交感神经系统激活是心力衰竭的主要特征。我们以前证明，增强中枢交感神经流出与脑Toll样受体4（TLR 4）可能介导的脑血管紧张素II 1型受体在心肌梗死（MI）诱导的心力衰竭小鼠。本研究的目的是检查是否沉默脑TLR 4可以防止MI诱导的心力衰竭中的LV重构与交感神经抑制。采用结扎左冠状动脉的方法建立心肌梗塞心衰模型。侧脑室注射hGAPDH-SiRNA后，MI心衰大鼠脑干TLR 4表达水平明显高于假手术组。侧脑室注射TLR 4-SiRNA治疗MI心衰组脑干TLR 4含量明显低于侧脑室注射hGAPDH-SiRNA治疗组。在用TLR 4-SiRNA治疗的MI诱导的心力衰竭中，肺重量、尿去甲肾上腺素排泄和LV舒张末期压显著低于用hGAPDH-SiRNA治疗2周的MI诱导的心力衰竭，并且LV尺寸显著小于用hGAPDH-SiRNA治疗2周的MI诱导的心力衰竭。通过ICV注射TLR 4-SiRNA 2周部分沉默脑TLR 4可部分防止MI诱导的心力衰竭大鼠的LV重构和交感神经抑制。脑TLR 4有可能成为心肌梗死心力衰竭治疗的靶点。
Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure. MI-induced heart failure model rats were created by ligation of left coronary artery. The expression level of TLR4 in brainstem was significantly higher in MI-induced heart failure treated with intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in brainstem was significantly lower in MI-induced heart failure treated with ICV injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA. Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were significantly lower and LV dimension was significantly smaller in MI-induced heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for 2 weeks. Partially silencing brain TLR4 by ICV injection of TLR4-SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of the treatment for MI-induced heart failure.
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影响因子：
2.1
作者：
Kishi T;Hirooka Y
通讯作者：
Hirooka Y
影响因子：
4.6
作者：
Patel, K P
通讯作者：
Patel, K P
DOI：
10.1152/ajpheart.00840.2004
发表时间：
2005-05-01
影响因子：
4.8
作者：
Huang, BS;Leenen, FHH
通讯作者：
Leenen, FHH
影响因子：
10.8
作者：
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通讯作者：
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影响因子：
20.1
作者：
Kimura, Y;Hirooka, Y;Sunagawa, K
通讯作者：
Sunagawa, K