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盐酸戊乙奎醚通过激活Nrf2信号通路改善小鼠肾缺血再灌注诱导的肺损伤。

Penehyclidine hydrochloride ameliorates renal ischemia reperfusion-stimulated lung injury in mice by activating Nrf2 signaling.

作者信息

Yang Qiang, Li Lei, Liu Zhaohui, Li Chunlei, Yu Lili, Chang Yulin

机构信息

Department of Anesthesiology, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China.

Physical Examination Center, Cangzhou Central Hospital, Teaching Hospital of Tianjin Medical University, Cangzhou 061000, Hebei, China.

出版信息

Bioimpacts. 2022;12(3):211-218. doi: 10.34172/bi.2021.23401. Epub 2021 Oct 30.

DOI:10.34172/bi.2021.23401
PMID:35677666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9124878/
Abstract

Penehyclidine hydrochloride (PHC) is an anticholinergic with anti-inflammatory and anti-oxidation activities. PHC displayed protectivity against renal ischemia reperfusion (RIR) injury. Nevertheless, the precise protectivity of PHC on RIR-induced lung injury remains unknown. We examined the effects of PHC on RIR-induced lung injury and investigated the underlying mechanism. We induced RIR in mice and administrated PHC to RIR mice. Kidney function was monitored by measuring the blood urea nitrogen (BUN) and creatinine level in serum. We evaluated the lung injury, myeloperoxidase (MPO) activity in lung, pro-inflammatory cytokine level, and oxidative markers in serum and lung tissues. We tested the expression level of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in lung of RIR mice after PHC treatment. Finally, we evaluated the effects of PHC in RIR Nrf2 mice. PHC greatly downregulated the serum levels of BUN, creatinine, IL-6, NO, malondialdehyde (MDA), and matrix metalloproteinase-2. PHC also ameliorated the lung injury, decreased the MPO activity, and suppressed production of IL-6, TNF-α, IFN-γ, MDA, and O2-, while it promoted production of superoxide dismutase (SOD) and catalase (CAT) in lung. PHC improved the production of Nrf2 and HO-1. The protectivity of PHC was absent in Nrf2 mice. PHC ameliorated RIR-induced lung injury through Nrf2 pathway.

摘要

盐酸戊乙奎醚(PHC)是一种具有抗炎和抗氧化活性的抗胆碱能药物。PHC对肾缺血再灌注(RIR)损伤具有保护作用。然而,PHC对RIR诱导的肺损伤的确切保护作用尚不清楚。我们研究了PHC对RIR诱导的肺损伤的影响,并探讨了其潜在机制。我们在小鼠中诱导RIR,并对RIR小鼠给予PHC。通过测量血清中的血尿素氮(BUN)和肌酐水平来监测肾功能。我们评估了肺损伤、肺组织中的髓过氧化物酶(MPO)活性、促炎细胞因子水平以及血清和肺组织中的氧化标志物。我们检测了PHC处理后RIR小鼠肺组织中核因子红细胞2相关因子2(Nrf-2)和血红素加氧酶1(HO-1)的表达水平。最后,我们评估了PHC对RIR Nrf2小鼠的影响。PHC显著下调了血清中BUN、肌酐、IL-6、NO、丙二醛(MDA)和基质金属蛋白酶-2的水平。PHC还改善了肺损伤,降低了MPO活性,并抑制了IL-6、TNF-α、IFN-γ、MDA和O2-的产生,同时促进了肺组织中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的产生。PHC提高了Nrf2和HO-1的产生。在Nrf2小鼠中,PHC的保护作用消失。PHC通过Nrf2途径改善了RIR诱导的肺损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/0adff77750e5/bi-12-211-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/5793e80ece09/bi-12-211-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/3534cf5a15aa/bi-12-211-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/24af6ca4f02d/bi-12-211-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/0c18d47c4388/bi-12-211-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/8259410ac771/bi-12-211-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/0adff77750e5/bi-12-211-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/5793e80ece09/bi-12-211-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/a75a6f3cb853/bi-12-211-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/3534cf5a15aa/bi-12-211-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/24af6ca4f02d/bi-12-211-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/0c18d47c4388/bi-12-211-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/8259410ac771/bi-12-211-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7077/9124878/0adff77750e5/bi-12-211-g007.jpg

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