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锌对 Wistar 大鼠长期低气压低氧右心血管环的影响。

Effects of Zinc on the Right Cardiovascular Circuit in Long-Term Hypobaric Hypoxia in Wistar Rats.

机构信息

Institute of Health Studies, University Arturo Prat, Av. Arturo Prat 2120, Iquique 1110939, Chile.

Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia and Its Health Sequelae, Hamburg (Germany) and Iquique (Chile), Avenida Arturo Prat 2120, Iquique 1110939, Chile.

出版信息

Int J Mol Sci. 2023 May 31;24(11):9567. doi: 10.3390/ijms24119567.

DOI:10.3390/ijms24119567
PMID:37298516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10253479/
Abstract

Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to receive either 1% Zn sulfate solution (z) or saline (s) intraperitoneally. Body weight, hemoglobin, and RVH were measured. Zn levels were evaluated in plasma and lung tissue. Additionally, the lipid peroxidation levels, HIF2α/MTF-1/MT/ZIP12/PKCε protein expression and pulmonary artery remodeling were measured in the lung. The CIH and CH groups showed decreased plasma Zn and body weight and increased hemoglobin, RVH, and vascular remodeling; the CH group also showed increased lipid peroxidation. Zn administration under hypobaric hypoxia upregulated the HIF2α/MTF-1/MT/ZIP12/PKCε pathway and increased RVH in the intermittent zinc group. Under intermittent hypobaric hypoxia, Zn dysregulation could participate in RVH development through alterations in the pulmonary HIF2α/MTF1/MT/ZIP12/PKCε pathway.

摘要

慢性低氧条件下的低压低氧会引发低氧性肺血管收缩（HPV）和右心室肥厚（RVH）。锌（Zn）在低氧环境下的作用存在争议，目前尚不清楚。我们评估了在长期低压低氧环境下补充 Zn 对肺和 RVH 中 HIF2α/MTF-1/MT/ZIP12/PKCε 通路的影响。Wistar 大鼠暴露于低压低氧环境中 30 天，并随机分为三组：慢性低氧（CH）；间歇性低氧（2 天低氧/2 天常氧；CIH）；和常氧（海平面对照；NX）。每组进一步分为（n = 8）接受腹腔内注射 1% Zn 硫酸盐溶液（z）或生理盐水（s）。测量体重、血红蛋白和 RVH。评估血浆和肺组织中的 Zn 水平。此外，还测量了肺中的脂质过氧化水平、HIF2α/MTF-1/MT/ZIP12/PKCε 蛋白表达和肺动脉重塑。CIH 和 CH 组的血浆 Zn 和体重降低，血红蛋白、RVH 和血管重塑增加；CH 组还表现出脂质过氧化增加。在低压低氧条件下给予 Zn 会上调 HIF2α/MTF-1/MT/ZIP12/PKCε 通路，并增加间歇性 Zn 组的 RVH。在间歇性低压低氧环境下，Zn 失调可能通过改变肺 HIF2α/MTF1/MT/ZIP12/PKCε 通路参与 RVH 的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e549/10253479/ee33f37c0e3a/ijms-24-09567-g006.jpg
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