Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China;
Department of Internal Medicine, Public Health Clinical Center, Affiliated to Shandong University, Jinan, Shandong, China.
Allergol Immunopathol (Madr). 2023 Mar 1;51(2):36-44. doi: 10.15586/aei.v51i2.701. eCollection 2023.
The purpose is to confirm whether long noncoding RNA relieves chronic intermittent hypoxia (CIH)-induced lung inflammation.
Male Sprague Dawley rats were used to establisha CIH rat model. Hematoxylin and Eosin staining was used on the lung tissue injury to determine the successful construction of CIH animal model. Arterial partial pressure of oxygen (PaO) and carbon dioxide (PaCO) were measured. was overexpressed to evaluate its role in the progression and development of CIH. T cell differentiation and cytokine production were determined using flow cytometry. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labelling assay kit. The target of and was predicted by the Encyclopedia of RNA Interactomes (ENCORI) and confirmed using luciferase assay.
was downregulated in CIH rat models. Lung tissue injury was observed in CIH rats, and the injury was attenuated by the overexpression of . PaO was reduced and PaCO was induced in CIH rats, which was reversed by the overexpression of . The overexpression of inhibited CIH-induced cell apoptosis. It also reversed alterations in the levels of interferon gamma (IFNγ), interleukin (IL)-2, IL-6, IL-1β, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) in rats caused by CIH. The overexpression of prevented the induction in CD4 IFN-γ T cells and reduction in CD4TGF-β1 T cells. The overexpression of upregulated tumor necrosis factor-alpha-induced protein 8-like 2 () key regulator through directly targeting . Further experiments proved that was the direct target of .
This study manifested that acted as an anti-inflammatory regulator and protected lung tissue injury from CIH in the rat model; this was mediated by upregulation of through directly targeting upregulated the expression of , providing new understanding and therapeutic target for CIH.
目的是确认长链非编码 RNA 是否能缓解慢性间歇性低氧（CIH）引起的肺部炎症。
使用雄性 Sprague Dawley 大鼠建立 CIH 大鼠模型。通过苏木精和伊红染色观察肺组织损伤，以确定 CIH 动物模型构建成功。测量动脉血氧分压（PaO）和二氧化碳分压（PaCO）。过表达以评估其在 CIH 进展和发展中的作用。使用流式细胞术测定 T 细胞分化和细胞因子产生。使用末端脱氧核苷酸转移酶 dUTP 缺口末端标记试剂盒测定细胞凋亡。通过 RNA 相互作用组百科全书（ENCORI）预测的靶标，并通过荧光素酶测定进行验证。
在 CIH 大鼠模型中下调。在 CIH 大鼠中观察到肺组织损伤，而过表达则减轻了损伤。在 CIH 大鼠中降低了 PaO 并诱导了 PaCO，而过表达则逆转了这一现象。过表达抑制了 CIH 诱导的细胞凋亡。它还逆转了 CIH 引起的大鼠中干扰素γ（IFNγ）、白细胞介素（IL）-2、IL-6、IL-1β、肿瘤坏死因子α（TNF-α）和转化生长因子β1（TGF-β1）水平的变化。过表达防止了 CD4 IFN-γ T 细胞的诱导和 CD4 TGF-β1 T 细胞的减少。过表达通过直接靶向上调肿瘤坏死因子-α诱导蛋白 8 样 2（）关键调节因子。进一步的实验证明是直接的靶标。
本研究表明，在大鼠模型中，作为一种抗炎调节剂，通过直接靶向上调，保护肺组织免受 CIH 损伤；这上调了的表达，为 CIH 提供了新的理解和治疗靶点。
