College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
Biol Trace Elem Res. 2022 Sep;200(9):4045-4057. doi: 10.1007/s12011-021-03011-7. Epub 2021 Nov 5.
Zinc (Zn) is an essential trace element for the body. Studies have confirmed that Zn deficiency can cause oxidative stress. The purpose of the present study was designed to investigate the effect of Zn on fibrosis in lung of mice and its mechanism. Mice were fed with different Zn levels dietary, then we found that the Zn-deficient diet induced a decrease of Zn level in lung tissue. The results also revealed the alveolar structure hyperemia and an inflammatory exudated in the alveolar cavity. Moreover, immunohistochemical results showed that the expression of α-smooth muscle actin (α-SMA) increased. And the Sirius red staining indicated an increase in collagen with Zn deficiency. Furthermore, oxygen radicals (ROS) levels were significantly increased, and the antioxidants were significantly decreased. Meanwhile, inflammatory factors (TNF-α and IL-1β) were remarkably increased, and the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) were detected by qPCR. The results showed that the expression of TIMPs was increased but the expression of MMPs was decreased. The results of the experiment in vitro were consistent with that in vivo. All the results indicated that Zn deficiency aggravated the oxidative stress response of lung tissue to induce inflammation, leading to fibrosis in lung.
锌(Zn)是人体必需的微量元素。研究证实,锌缺乏可导致氧化应激。本研究旨在探讨锌对小鼠肺纤维化的影响及其机制。用不同锌水平的饮食喂养小鼠,然后我们发现缺锌饮食诱导肺组织中锌水平降低。结果还显示肺泡结构充血和肺泡腔中有炎症渗出物。此外,免疫组织化学结果显示α-平滑肌肌动蛋白(α-SMA)的表达增加。而且天狼星红染色表明胶原缺乏导致胶原增加。此外,氧自由基(ROS)水平显著升高,抗氧化剂显著降低。同时,炎症因子(TNF-α和IL-1β)显著增加,ELISA 结果表明胶原 I、III、IV 和纤维连接蛋白(FN)增加。此外,通过 qPCR 检测了基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)的表达。结果表明 TIMPs 的表达增加,但 MMPs 的表达减少。体外实验结果与体内结果一致。所有结果表明,锌缺乏加重了肺组织的氧化应激反应,导致炎症,进而导致肺纤维化。