Gao Zhen, Halmurat Upur, Wang Jing, Jing Jing, Li Zheng, Xu Dan, Li Fengsen
J Tradit Chin Med. 2016 Oct;36(5):671-7. doi: 10.1016/s0254-6272(16)30088-7.
To reveal the effects on expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease (COPD) and a cold-dryness symptom pattern induced by elastase and smoking.
The COPD model was established with an elastase dose into the trachea combined with exposure to smoking; the COPD model cold-dryness symptom pattern was further developed by exposure to a cold, dry environment. After 90 days, pathologic lung sections, inflammatory cytokine levels (measured by enzyme linked immunosorbent assay), mRNA and protein expression of mucus-associated proteins and aquaporins (measured by real-time polymerase chain reaction and western blots) were examined.
Cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in the COPD and the cold-dryness symptom pattern COPD groups were all significantly higher than in controls (each P < 0.01). IL-6 and IL-8 levels were higher in the cold-dryness symptom pattern COPD group than in the COPD group (each P < 0.05). The AQP5 mRNA expression in the cold-dryness symptom pattern COPD and COPD groups was lower than in the control group (P < 0.01), and that in the cold-dryness symptom pattern COPD group was lower than the COPD group (P < 0.05). The expression of MUC5AC and MUC5B mRNAs in the cold-dryness symptom pattern COPD group and COPD group was higher than in the control group (each P < 0.01), and that in the cold-dryness symptom pattern COPD group was higher than the COPD group (P < 0.01, and P < 0.05, respectively). The ratio of MUC5AC mRNA/MUC5B mRNA was COPD group < the cold-dryness symptom pattern COPD group < the control group. AQP4 and AQP5 protein expression in the cold-dryness symptom pattern COPD group was lower than that in the COPD group which was lower again than in the control group. MUC5AC and MUC5B expression in the cold-dryness symptom pattern COPD group was higher than in the COPD group and higher again than in the control group.
Cold-dryness affects the expression of mucus-associated protein mRNA and its corresponding proteins, reducing the secretion of aquaporins and increasing the secretion of mucins. Imbalance in aquaporins and mucins can affect the function of mucus, increasing airway obstruction.
揭示弹性蛋白酶和吸烟诱导的慢性阻塞性肺疾病(COPD)兼寒燥证大鼠气道黏液相关蛋白表达的变化。
采用气管内注入弹性蛋白酶并结合烟熏建立COPD模型;通过置于寒冷干燥环境进一步建立COPD兼寒燥证模型。90天后,检测肺组织病理切片、炎症细胞因子水平(采用酶联免疫吸附测定法)、黏液相关蛋白和水通道蛋白的mRNA及蛋白表达(采用实时聚合酶链反应和蛋白质印迹法)。
COPD组和COPD兼寒燥证组的细胞因子白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)均显著高于对照组(均P<0.01)。COPD兼寒燥证组的IL-6和IL-8水平高于COPD组(均P<0.05)。COPD兼寒燥证组和COPD组的水通道蛋白5(AQP5)mRNA表达低于对照组(P<0.01),且COPD兼寒燥证组低于COPD组(P<0.05)。COPD兼寒燥证组和COPD组的黏蛋白5AC(MUC5AC)和黏蛋白5B(MUC5B)mRNA表达高于对照组(均P<0.01),且COPD兼寒燥证组高于COPD组(分别为P<0.01和P<0.05)。MUC5AC mRNA/MUC5B mRNA比值为COPD组<COPD兼寒燥证组<对照组。COPD兼寒燥证组的水通道蛋白4(AQP4)和AQP5蛋白表达低于COPD组,COPD组又低于对照组。COPD兼寒燥证组的MUC5AC和MUC5B表达高于COPD组,COPD组又高于对照组。
寒燥影响黏液相关蛋白mRNA及其相应蛋白的表达,减少水通道蛋白的分泌,增加黏蛋白的分泌。水通道蛋白与黏蛋白失衡会影响黏液功能,加重气道阻塞。