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富含甲烷的盐水通过调节 TLR4/NF-B/NLRP3 炎性小体通路来对抗胆汁淤积性肝损伤。

Methane-Rich Saline Counteracts Cholestasis-Induced Liver Damage via Regulating the TLR4/NF-B/NLRP3 Inflammasome Pathway.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Department of the First General Surgery, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China.

出版信息

Oxid Med Cell Longev. 2019 Nov 18;2019:6565283. doi: 10.1155/2019/6565283. eCollection 2019.

Abstract

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-B pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-B subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-B/NLRP3 signaling pathway.

摘要

胆汁淤积性肝损伤由于胆道阻塞或遗传缺陷,常伴有进行性炎症和肝纤维化。富含甲烷的盐水(MRS)具有抗炎作用。然而,MRS 是否能在胆汁淤积性肝损伤中提供保护作用尚不清楚。在这项研究中,Sprague-Dawley 大鼠接受胆管结扎(BDL)以生成胆汁淤积模型,然后在手术后每 12 小时用 MRS(10mL/kg,ip 治疗)处理,以探索 MRS 在胆汁淤积性肝损伤中的潜在保护机制。我们发现 MRS 能有效改善肝功能,减轻肝组织病理损伤和局部炎症细胞浸润。MRS 处理降低了肝纤维化相关蛋白的表达,从而减轻肝纤维化。此外,MRS 处理抑制了 TLR4/NF-B 通路,进一步降低了促炎因子的水平。NF-B 的下调随后降低了 NLRP3 的表达,从而抑制了细胞焦亡。我们的数据表明,甲烷处理通过涉及 TLR4/NF-B/NLRP3 信号通路的抗炎特性来预防胆汁淤积性肝损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e41/6885841/3e1033ea4ce7/OMCL2019-6565283.001.jpg

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