Renal Denervation Attenuates Neuroinflammation in the Brain by Regulating Gut-Brain Axis in Rats With Myocardial Infarction.
Renal Denervation Attenuates Neuroinflammation in the Brain by Regulating Gut-Brain Axis in Rats With Myocardial Infarction.
复制标题
肾去神经支配通过调节心肌梗死大鼠的肠脑轴来减轻大脑中的神经炎症
DOI：
10.3389/fcvm.2021.650140
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发表时间：
2021
影响因子：
3.6
通讯作者：
Shan QJ
中科院分区：
文献类型：
--
作者：
Huo JY;Jiang WY;Lyu YT;Zhu L;Liu HH;Chen YY;Chen M;Geng J;Jiang ZX;Shan QJ
目的：神经炎症的发展恶化了心肌梗死（MI）的预后。本研究旨在探讨去肾神经支配（RDN）对大鼠心肌梗死后神经炎症的影响及其机制。方法和结果：雄性成年SD大鼠进行假手术或结扎左冠状动脉前降支诱导MI。一周后，MI大鼠接受假手术或RDN手术。通过超声心动图分析其心功能，并检测其肠道结构、通透性和炎性细胞因子。通过16 S rDNA测序对肠道微生物群进行表征。通过小胶质细胞活化、炎性细胞因子和炎症相关信号通路分析大鼠脑中神经炎症的程度。与对照组大鼠相比，MI大鼠表现出心脏功能受损、肠损伤、肠屏障通透性增加和微生物生态失调，伴有脑中小胶质细胞活化和促炎细胞因子水平增加。RDN手术显著降低了MI大鼠肾脏和肠交感神经活动的水平，改善了心脏功能，减轻了MI相关的肠损伤和脑中的神经炎症。有趣的是，RDN程序减轻了MI增加的肠屏障通透性和促炎细胞因子和血浆LPS，并改善了MI大鼠的肠道微生物生态失调。RDN对MI大鼠心肌的保护作用不受肠碱性磷酸酶治疗的影响，但受L-苯丙氨酸治疗的影响。结论：RDN可减轻MI大鼠脑内神经炎症反应，其机制可能与减轻MI相关的肠损伤有关。
Aims: The development of neuroinflammation deteriorates the prognosis of myocardial infarction (MI). We aimed to investigate the effect of renal denervation (RDN) on post-MI neuroinflammation in rats and the related mechanisms. Methods and Results: Male adult Sprague-Dawley rats were subjected to sham or ligation of the left anterior descending coronary artery to induce MI. One week later, the MI rats received a sham or RDN procedure. Their cardiac functions were analyzed by echocardiography, and their intestinal structures, permeability, and inflammatory cytokines were tested. The intestinal microbiota were characterized by 16S rDNA sequencing. The degrees of neuroinflammation in the brains of rats were analyzed for microglia activation, inflammatory cytokines, and inflammation-related signal pathways. In comparison with the Control rats, the MI rats exhibited impaired cardiac functions, intestinal injury, increased intestinal barrier permeability, and microbial dysbiosis, accompanied by increased microglia activation and pro-inflammatory cytokine levels in the brain. A RDN procedure dramatically decreased the levels of renal and intestinal sympathetic nerve activity, improved cardiac functions, and mitigated the MI-related intestinal injury and neuroinflammation in the brain of MI rats. Interestingly, the RDN procedure mitigated the MI-increased intestinal barrier permeability and pro-inflammatory cytokines and plasma LPS as well as ameliorated the gut microbial dysbiosis in MI rats. The protective effect of RDN was not significantly affected by treatment with intestinal alkaline phosphatase but significantly reduced by L-phenylalanine treatment in MI rats. Conclusions: RDN attenuated the neuroinflammation in the brain of MI rats, associated with mitigating the MI-related intestinal injury.