|Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats|
|Lin Ying1; Zhu Xi1; Yao Wan-zhen2; Yang Yan-lin3; La-ta, A.3; Chen Li3|
|关键词||Acute Lung Injury Alpha 2a Adrenergic Receptor Inflammatory Response|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||RESPIRATORY-DISTRESS-SYNDROME ; MEDICAL PROGRESS ; LIPOPOLYSACCHARIDE ; INFLAMMATION ; SEPSIS ; MODEL ; MICE|
Background Alpha 2A adrenergic receptor (AR) is a subtype of alpha 2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the alpha 2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of alpha 2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats.
Methods A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 mu g), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of alpha 2A AR on inflammatory cells in BALF.
Results When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as alpha 2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-alpha and IL-1 beta were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-alpha, IL-1 beta and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-alpha and IL-1 beta were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-alpha, IL-1 beta and IL-6 in the BALF and the lung histopathological scores (r=0.703, r=0.595, r=0.487 and r=0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to alpha 2A AR on inflammatory cells were also associated with the levels of TNF-alpha, IL-1 beta and IL-6 as well as the lung histopathologial scores (r=0.803, r=0.978, r=0.716 and r=0.808, respectively, P < 0.001).
Conclusions Yohimbine can inhibit TNF-alpha, IL-1 beta and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of alpha 2A AR on inflammatory cells. Chin Med J 2011;124(7):1069-1074
|资助机构||Capital Development Project|
|作者单位||1.Peking Univ, Hosp 3, Cent Lab, Beijing 100191, Peoples R China|
2.Peking Univ, Hosp 3, Dept Surg, Intens Care Unit, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Dept Resp Med, Beijing 100191, Peoples R China
|Lin Ying,Zhu Xi,Yao Wan-zhen,et al. Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats[J]. CHINESE MEDICAL JOURNAL,2011,124(7):1069-1074.|
|APA||Lin Ying,Zhu Xi,Yao Wan-zhen,Yang Yan-lin,La-ta, A.,&Chen Li.(2011).Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats.CHINESE MEDICAL JOURNAL,124(7),1069-1074.|
|MLA||Lin Ying,et al."Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats".CHINESE MEDICAL JOURNAL 124.7(2011):1069-1074.|