Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure.
Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure.
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肠屏障功能障碍通过 TLR4 通路加剧心力衰竭小鼠的神经炎症
DOI：
10.3389/fphys.2021.712338
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发表时间：
2021
影响因子：
4
通讯作者：
Shan QJ
中科院分区：
文献类型：
--
作者：
Huo JY;Jiang WY;Yin T;Xu H;Lyu YT;Chen YY;Chen M;Geng J;Jiang ZX;Shan QJ
本研究旨在探讨心力衰竭（HF）后神经炎症的变化及其可能机制。对雄性野生型（WT）和Toll样受体4（TLR 4）敲除（KO）小鼠进行假手术或结扎左冠状动脉前降支以诱导HF。8周后，通过超声心动图检测心脏功能，通过测定紧密连接蛋白表达、肠通透性和血浆代谢物水平检测肠屏障功能。通过测量小胶质细胞活化、炎性细胞因子水平和促炎信号通路来检查脑中神经炎症的改变。应用肠屏障保护剂肠碱性磷酸酶（IAP）和肠内稳态抑制剂L-苯丙氨酸（L-Phe）研究HF小鼠肠屏障功能障碍与神经炎症的关系。8周后，HF WT小鼠肠通透性和血浆脂多糖（LPS）水平明显升高，同时伴有脑内TLR 4表达增加和神经炎症反应增强。用肠屏障保护剂IAP治疗显著减轻HF后的神经炎症，同时有效地增加血浆LPS水平。TLR 4-KO小鼠在HF诱导的神经炎症中表现出显著改善，这不受肠屏障抑制剂或保护剂的显著影响。HF可导致肠屏障功能障碍，增加LPS的肠-血转运，进而通过TLR 4途径促进神经炎症反应。
The present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms. Male wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF. Eight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors. HF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.
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影响因子：
9.9
作者：
Okello, A.;Edison, P.;Brooks, D. J.
通讯作者：
Brooks, D. J.
影响因子：
5.6
作者：
Drapala A;Szudzik M;Chabowski D;Mogilnicka I;Jaworska K;Kraszewska K;Samborowska E;Ufnal M
通讯作者：
Ufnal M
影响因子：
18.2
作者：
Huynh, Quan L.;Whitmore, Kristyn;Marwick, Thomas H.
通讯作者：
Marwick, Thomas H.
DOI：
10.1073/pnas.1220180110
发表时间：
2013-04-23
影响因子：
11.1
作者：
Kaliannan, Kanakaraju;Hamarneh, Sulaiman R.;Hodin, Richard A.
通讯作者：
Hodin, Richard A.
影响因子：
13.8
作者：
Offer, Alison;Arnold, Matthew;Parish, Sarah
通讯作者：
Parish, Sarah