Zhang Mingjing, Liu Xiaogang, Wu Jie, Yu Yijun, Wang Yuting, Gu Ye
Department of Cardiology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Physiol. 2020 May 14;11:375. doi: 10.3389/fphys.2020.00375. eCollection 2020.
We previously reported that bilateral sympathetic stellate ganglionectomy attenuated cardiac remodeling and fibrosis in rats with chronic volume overload. Transforming growth factor beta 1 (TGF-β1) is a polypeptide member of the transforming growth factor beta superfamily of cytokines and actively involved in many pathological processes of cardiovascular diseases. The present study explored the impact of bilateral sympathetic stellate ganglionectomy on the TGF-β1 pathway in this model. Male Sprague-Dawley rats were randomly divided into sham (S) group, abdominal aorta-cava fistula (AV) group, and bilateral sympathetic stellate ganglionectomy after abdominal aorta-cava fistula (AD) group. Twelve weeks after the abdominal aorta-cava fistula surgery, the myocardial expressions of norepinephrine (NE) and hydroxyproline were significantly higher, while acetylcholine was downregulated in the AV group compared to the S group; the above changes were partly reversed in the AD group. The myocardial expression of TGF-β1 and activity of Smad2/3 phosphorylation were also upregulated in the AV group compared to the S group, which could be reversed by bilateral sympathetic stellate ganglionectomy. , the TGF-β1 expression in cultured myocardial fibroblasts and the proliferation of myocardial fibroblasts were significantly increased post-stimulation with NE in a dose-dependent manner, and these effects could be blunted by co-treatment with a TGF-β1 inhibitor. Our study results indicate that stellate ganglionectomy decreases cardiac norepinephrine release, which leads to decreased TGF-β1 release and reduced fibrosis in rats with chronic volume overload.
我们之前报道过,双侧交感神经节切除术可减轻慢性容量超负荷大鼠的心脏重塑和纤维化。转化生长因子β1(TGF-β1)是转化生长因子β细胞因子超家族的多肽成员,积极参与心血管疾病的许多病理过程。本研究探讨了双侧交感神经节切除术对该模型中TGF-β1通路的影响。雄性Sprague-Dawley大鼠随机分为假手术(S)组、腹主动脉-腔静脉瘘(AV)组和腹主动脉-腔静脉瘘后双侧交感神经节切除术(AD)组。腹主动脉-腔静脉瘘手术后12周,与S组相比,AV组心肌中去甲肾上腺素(NE)和羟脯氨酸的表达显著升高,而乙酰胆碱表达下调;AD组上述变化部分得到逆转。与S组相比,AV组心肌中TGF-β1的表达和Smad2/3磷酸化活性也上调,双侧交感神经节切除术可使其逆转。此外,用NE刺激培养的心肌成纤维细胞后,TGF-β1表达和心肌成纤维细胞增殖呈剂量依赖性显著增加,而与TGF-β1抑制剂联合处理可减弱这些作用。我们的研究结果表明,星状神经节切除术可减少慢性容量超负荷大鼠心脏去甲肾上腺素的释放,从而导致TGF-β1释放减少和纤维化减轻。