No.3 Respiratory Department, Jiangxi Provincial Chest Hospital, Nanchang, Jiangxi, China (mainland).
Department of Science and Education, Jiangxi Provincial Chest Hospital, Nanchang, Jiangxi, China (mainland).
Med Sci Monit. 2018 Jan 18;24:356-362. doi: 10.12659/msm.905509.
BACKGROUND This study aimed to investigate the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on airway changes in chronic obstructive pulmonary disease (COPD) rats exposed to air pollutant particles less than 2.5 micrometers in diameter (PM2.5), and to evaluate the mechanisms. MATERIAL AND METHODS Three groups were included in this study: a normal group, a COPD model group, and a COPD with 1,25(OH)2D3 treatment group. In each group, the rats were divided into four subgroups: control and different doses of PM2.5 (1.6, 8 and 40 mg/kg body weight). Apoptosis in lung tissue was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of c-Jun N-terminal kinase 1 (JNK1) and mucin 5AC (MUC5AC) were detected by real-time polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence staining. RESULTS Compared with corresponding subgroups in normal group, the apoptotic rates in COPD group were significantly increased. By contrast, 1,25(OH)2D3 treatment group significantly reduced COPD-induced apoptosis in lung tissue. Upon the dose increase of PM2.5, the apoptotic rate was also elevated in each group. Compared with the corresponding control in each group, PM2.5 increased apoptosis in a dose-dependent manner. Importantly, 1,25(OH)2D3 also prevented apoptosis in COPD rats exposed to PM2.5. Mechanically, the expression of MUC5AC and JNK1 in COPD group was significantly upregulated, compared with corresponding subgroups in the normal group. Treatment with 1,25(OH)2D3 reduced expression of MUC5AC and JNK1 in COPD rats. It was found that the expression of MUC5AC and JNK1 was elevated with the dose increase of PM2.5 in each group. Consistently, 1,25(OH)2D3 also reduced the expression of MUC5AC and JNK1 in COPD rats exposed to PM2.5. CONCLUSIONS 1,25(OH)2D3 prevented lung injury in COPD rats with or without PM2.5 exposure. Our results suggest that 1,25(OH)2D3 is useful to mitigate the injury caused by COPD.
本研究旨在探讨 1,25-二羟维生素 D3（1,25(OH)2D3）对暴露于直径小于 2.5 微米的空气污染物颗粒（PM2.5）的慢性阻塞性肺疾病（COPD）大鼠气道变化的影响，并评估其机制。
本研究包括三组：正常组、COPD 模型组和 COPD 加 1,25(OH)2D3 治疗组。在每组中，大鼠又分为四个亚组：对照组和不同剂量的 PM2.5（1.6、8 和 40mg/kg 体重）。采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记法（TUNEL）检测肺组织细胞凋亡。实时聚合酶链反应（RT-PCR）、Western blot 和免疫荧光染色检测 c-Jun N 末端激酶 1（JNK1）和粘蛋白 5AC（MUC5AC）的表达。
与正常组相应亚组相比，COPD 组细胞凋亡率显著升高；而 1,25(OH)2D3 治疗组可显著降低 COPD 大鼠肺组织诱导的细胞凋亡。随着 PM2.5 剂量的增加，各组细胞凋亡率也逐渐升高；与各组相应对照组相比，PM2.5 呈剂量依赖性诱导细胞凋亡。重要的是，1,25(OH)2D3 还可预防 COPD 大鼠暴露于 PM2.5 时的细胞凋亡。机制上，与正常组相应亚组相比，COPD 组 MUC5AC 和 JNK1 的表达明显上调；1,25(OH)2D3 治疗降低了 COPD 大鼠 MUC5AC 和 JNK1 的表达。结果发现，各组中 PM2.5 剂量增加时 MUC5AC 和 JNK1 的表达也随之升高；1,25(OH)2D3 也降低了 COPD 大鼠暴露于 PM2.5 时 MUC5AC 和 JNK1 的表达。
1,25(OH)2D3 可预防 COPD 大鼠暴露于或不暴露于 PM2.5 时的肺损伤。我们的结果表明，1,25(OH)2D3 有助于减轻 COPD 引起的损伤。
