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三种新鲜制剂通过雌激素受体途径改善脂多糖诱导的脓毒症急性肾损伤的作用。

Effects of three types of fresh improve lipopolysaccharide-induced acute kidney injury in sepsis through the estrogen receptor pathway.

作者信息

Liu Meng, Zeng Mengnan, Guo Pengli, Zhang Yuhan, Yang Xiaofeng, Jia Jufang, Zhang Qinqin, Zhang Beibei, Cao Bing, Wang Ru, Zheng Xiaoke, Feng Weisheng

机构信息

Department of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, China.

The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou 450046, China.

出版信息

Iran J Basic Med Sci. 2023;26(5):579-586. doi: 10.22038/IJBMS.2023.67322.14757.

DOI:10.22038/IJBMS.2023.67322.14757
PMID:37051100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10083830/
Abstract

OBJECTIVES

To explore the effects and mechanism of three types of fresh , namely Beijing No. 3 (BJ3H), Huaizhong No. 1 (HZ1H), and Taisheng (TS) on lipopolysaccharide (LPS)-induced acute kidney injury in the sepsis (S-AKI) mice model through the estrogen receptor pathway.

MATERIALS AND METHODS

BALB/c mice were randomly divided into control (CON), model (LPS), astragalus injection (ASI), BJ3H, HZ1H, TS water extract groups, the estrogen receptor antagonist ICI182,780 groups were added to each group. The antagonist groups received an intraperitoneal injection of ICI 0.5 hr before administration and an intraperitoneal injection of LPS 3 days after administration. The kidney pathology, function, inflammatory factors, immune cells, levels of reactive oxygen species (ROS), apoptosis, and the protein expression levels of TLR4/NF-κB/NLRP3 signaling pathway in the mice kidneys were detected.

RESULTS

ASI, BJ3H, HZ1H, and TS improved LPS-induced renal pathology in S-AKI mice, reduced the kidney and serum levels of inflammatory factors, positive rates of macrophages and neutrophils, levels of ROS and apoptosis, and the relative expression levels of TLR4, MyD88, NF-κB p-p65/NF-κB p65, and NLRP3 proteins in the kidney. In addition, they increased the positive rate of dendritic cells (DCs) in the mice kidneys. The overall effect of HZ1H was superior to that of ASI, BJ3H, and TS. However, after adding ICI, the regulatory effects of drugs were inhibited.

CONCLUSION

The three types of fresh may completely or partially affect the TLR4/NF-κB/NLRP3 signaling pathway through the estrogen receptor pathway to exert a protective effect on S-AKI.

摘要

目的

通过雌激素受体途径探讨北京3号(BJ3H)、怀仲1号(HZ1H)和太生(TS)三种鲜药对脂多糖(LPS)诱导的脓毒症急性肾损伤(S-AKI)小鼠模型的影响及其机制。

材料与方法

将BALB/c小鼠随机分为对照组(CON)、模型组(LPS)、黄芪注射液(ASI)组、BJ3H组、HZ1H组、TS水提物组,每组再加入雌激素受体拮抗剂ICI182,780组。拮抗剂组在给药前0.5小时腹腔注射ICI,给药后3天腹腔注射LPS。检测小鼠肾脏的病理、功能、炎症因子、免疫细胞、活性氧(ROS)水平、细胞凋亡以及TLR4/NF-κB/NLRP3信号通路的蛋白表达水平。

结果

ASI、BJ3H、HZ1H和TS改善了LPS诱导的S-AKI小鼠的肾脏病理,降低了肾脏和血清中的炎症因子水平、巨噬细胞和中性粒细胞阳性率、ROS水平和细胞凋亡,以及肾脏中TLR4、MyD88、NF-κB p-p65/NF-κB p65和NLRP3蛋白的相对表达水平。此外,它们增加了小鼠肾脏中树突状细胞(DCs)的阳性率。HZ1H的总体效果优于ASI、BJ3H和TS。然而,加入ICI后,药物的调节作用受到抑制。

结论

三种鲜药可能通过雌激素受体途径完全或部分影响TLR4/NF-κB/NLRP3信号通路,从而对S-AKI发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/a6ccdd778503/IJBMS-26-579-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/d68e53bd3c2f/IJBMS-26-579-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/40b41194eb30/IJBMS-26-579-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/489f98991a71/IJBMS-26-579-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/16d574d611aa/IJBMS-26-579-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/a6ccdd778503/IJBMS-26-579-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/d68e53bd3c2f/IJBMS-26-579-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/40b41194eb30/IJBMS-26-579-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/489f98991a71/IJBMS-26-579-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/16d574d611aa/IJBMS-26-579-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a307/10083830/a6ccdd778503/IJBMS-26-579-g005.jpg

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