Effect of Doxofylline on Reducing the Inflammatory Response in Mechanically Ventilated Rats with Chronic Obstructive Pulmonary Disease

Chu-Yun Liu,1 Jian-Hua Wu,1 Zhi-Yuan Chen,1 Yi Zhang,1 Chun-Ling Huang,2 Ai-Mei Lin,1 Xiao-Ting Xu,1 Xiao-Hua Gao1 1Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 2Department of Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of ChinaCorrespondence: Zhi-Yuan ChenDepartment of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of ChinaTel +86 595-26655108Fax +86 595-22770258Email chen_tyty@163.comObjective: To evaluate the effect of doxofylline on reducing the inflammatory response in mechanically ventilated rats with chronic obstructive pulmonary disease (COPD).Methods: A total of 40 eight-week-old male Sprague Dawley rats were randomly divided into four groups of 10 rats each: a control group (group C), a model group (group M), a model + natural saline group (group N), and a doxofylline group (group D). Then mechanical ventilation, drug intervention, and the extraction of the experimental material were performed in each group. Pulmonary tissue samples were taken after 120 minutes of mechanical ventilation and the pulmonary histopathological changes and the wet/dry (W/D) weight ratio of the pulmonary tissue were identified. The levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected using an enzyme-linked immunosorbent assay, and the expression levels of c-Jun-N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected using immunohistochemistry.Results: Compared with group C, the pulmonary histopathology in groups M, N, and D showed typical changes associated with COPD. Furthermore, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue increased in groups M, N, and D (P < 0.05), while the levels of IL-10 decreased (P < 0.05). Compared with group M, no statistically significant changes in the above indicators were detected in the pulmonary tissue of group N (P > 0.05). Compared with group N, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue decreased in group D (P < 0.05), while the levels of IL-10 increased (P < 0.05).Conclusion: Doxofylline might attenuate pulmonary inflammatory responses in mechanically ventilated rats with COPD, and the JNK/stress-activated protein kinase signaling pathway is involved in doxofylline’s inhibition of inflammatory responses in the pulmonary tissue of rats with COPD.Keywords: chronic obstructive pulmonary disease, TNF-α, IL-10, JNK, p-JNK