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祛瘀活血方对非酒精性脂肪性肝炎模型小鼠SOCS1/TLR4信号通路的影响

Effects of Qutan Huoxue Formula on the SOCS1/TLR4 Signaling Pathway in NASH Model Mice.

作者信息

Zhang Yurong, Zhu Xiaoning, Zheng Ding, Yin Yue, Peng Mengyun, Wang Jing

机构信息

Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China.

出版信息

Evid Based Complement Alternat Med. 2020 Nov 20;2020:1570918. doi: 10.1155/2020/1570918. eCollection 2020.

Abstract

The purpose of this study was to investigate the effects of Qutan Huoxue Formula (QHF) on liver injury in mice with nonalcoholic steatohepatitis (NASH) by upregulating SOCS1 to inhibit the TLR4/NF-B signaling pathway. Thirty male C57BL/6J mice (20-22 g) were randomly divided into the normal diet group (ND group), methionine- and choline-deficient diet group (MCD group), and Qutan Huoxue Formula group (QHF group). Mice in the ND group were fed a regular diet, while mice in other two groups were fed MCD diet. After successful molding, the QHF group was gavaged by QHF. The ND group and MCD group were gavaged by the same volume of normal saline, once a day. During the period of gavaging, all mice continue to be fed MCD fodder except for the ND group. All mice were killed at 8 w. H&E staining and Oil Red O staining were used to observe the pathological changes of liver tissues. Serum level of ALT, AST, TC, and TG was detected by enzyme-linked immunosorbent assay. The expression of liver SOCS1, TLR4, Myd88, and NF-B was detected by real-time PCR, immunohistochemistry, and Western blot. QHF can significantly reduce the serum levels of ALT, AST, TC, and TG of NASH mice and reduce the degree of liver fat degeneration and inflammation. It also can decrease both mRNA and protein expressions of liver TLR4, Myd88, and NF-B. The mRNA expression of SOCS1 increased, while the SOCS1 protein expression decreased. In conclusion, QHF can significantly alleviate hepatic steatosis and inflammation in NASH mice by upregulating SOCS1 to inhibit the TLR4/NF-B signaling pathway.

摘要

本研究旨在通过上调SOCS1以抑制TLR4/NF-κB信号通路,探讨祛瘀活血方(QHF)对非酒精性脂肪性肝炎(NASH)小鼠肝损伤的影响。将30只雄性C57BL/6J小鼠(20-22克)随机分为正常饮食组(ND组)、蛋氨酸和胆碱缺乏饮食组(MCD组)和祛瘀活血方组(QHF组)。ND组小鼠给予常规饮食,而其他两组小鼠给予MCD饮食。造模成功后,QHF组给予QHF灌胃。ND组和MCD组给予等体积生理盐水灌胃,每日1次。在灌胃期间,除ND组外,所有小鼠继续给予MCD饲料。所有小鼠在8周时处死。采用苏木精-伊红(H&E)染色和油红O染色观察肝组织病理变化。采用酶联免疫吸附测定法检测血清ALT、AST、TC和TG水平。采用实时荧光定量PCR、免疫组织化学和蛋白质印迹法检测肝脏SOCS1、TLR4、Myd88和NF-κB的表达。QHF可显著降低NASH小鼠血清ALT、AST、TC和TG水平,减轻肝脏脂肪变性和炎症程度。它还可降低肝脏TLR4、Myd88和NF-κB的mRNA和蛋白表达。SOCS1的mRNA表达增加,而SOCS1蛋白表达降低。综上所述,QHF可通过上调SOCS1抑制TLR4/NF-κB信号通路,显著减轻NASH小鼠的肝脂肪变性和炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e542/7700041/31cfcd5cb771/ECAM2020-1570918.001.jpg

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