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目的探讨严重急性呼吸综合征(SARS)冠状病毒N蛋白所致大鼠肺部炎症反应及糖皮质激素(以下简称激素)对其的调节作用。方法24只SD大鼠随机分为4组,每组6只;A组大鼠气管内滴入无菌生理盐水0.2ml,B组(6h)、C组(24h)大鼠气管内滴入SARS病毒N蛋白溶液0.2ml,D组大鼠气管内滴入SARS病毒N蛋白溶液0.2ml的同时腹腔内注射10mg/kg地塞米松。测4组大鼠外周血、支气管肺泡灌洗液(BALF)中WBC总数及分类;测4组大鼠肺组织湿/干(W/D)比值;观察4组大鼠肺组织病理学变化;ELISA测4组大鼠血清及BALF中IL6、IL10、转化生长因子(TGF)β1水平。结果(1)外周血淋巴细胞比例C组较A组低(P<0.05),D组较A、C组均低(P值均小于0.01);D组WBC总数较A、C组均低(P<0.01)。BALF中WBC总数C组较A组高(P<0.05),D组较C组低(P<0.05);B、C组BALF中肺泡巨噬细胞占98%～99%。(2)肺脏W/D比值B、C组较A组高(P<0.05),D组较C组低(P<0.01)。(3)肺组织病理学变化:B、C组大鼠肺泡间隔明显增宽,有较多的炎性细胞渗出,包括中性粒细胞、淋巴细胞、单核细胞、成纤维细胞等,血管充血、淤血,有的支气管腔内有炎性细胞渗出,C组变化较B组无明显加重;D组大鼠肺组织炎性反应较B、C组减轻,肺泡间隔变薄,炎性细胞渗出减少。(4)血清及BALF中IL6、IL10、TGFβ1水平B组较A组高(P<0.01),C组进一步升高(P<0.01),D组较C组低(P<0.01)。结论SARS冠状病毒N蛋白具有致病性,能够引起大鼠肺部炎症反应和(或)急性肺损伤,肺损伤与促炎性细胞因子、抗炎性细胞因子的升高及失衡有关;激素可有效地减轻SARS冠状病毒N蛋白所致的肺部炎症反应。
Objective To investigate the pulmonary inflammatory response induced by severe acute respiratory syndrome (SARS) coronavirus N protein and the regulatory effect of glucocorticoids (Hormone) on them. Methods Twenty-four SD rats were randomly divided into 4 groups with 6 rats in each group. Rats in group A were injected with 0.2 ml sterile saline into trachea, Group B (6 h) and group C Virus N protein solution 0.2ml, Group D rats tracheal instillation of SARS virus N protein solution 0.2ml while intraperitoneal injection of 10mg / kg dexamethasone. The total number and classification of WBC in the peripheral blood and bronchoalveolar lavage fluid (BALF) of the four groups were measured. The wet / dry (W / D) ratio of the lungs of the four groups was measured. The pathological changes of the lungs of the four groups were observed. The levels of IL6, IL10 and transforming growth factor (TGF) β1 in the serum and BALF were measured by ELISA. Results (1) The proportion of peripheral blood lymphocytes in group C was lower than that in group A (P <0.05), in group D was lower than that in group A and C (all P values were less than 0.01) P <0.01). The total number of WBC in BALF was higher in group C than in group A (P <0.05), in group D was lower than that in group C (P <0.05). In group B and C, alveolar macrophages accounted for 98% -99% of BALF. (2) The lung W / D ratio B, C group was higher than A group (P <0.05), D group was lower than C group (P <0.01). (3) Pathological changes of lung tissue: The alveolar septa of rats in groups B and C were obviously broadened with more exudative inflammatory cells, including neutrophils, lymphocytes, monocytes, fibroblasts, etc. Congestion, congestion, and some bronchial lumen exudative inflammatory cells, C group changes were not significantly worse than the B group; D group rats lung tissue inflammatory response than the B, C group, alveolar septum thinning, inflammatory cells Reduce oozing. (4) The levels of IL6, IL10 and TGFβ1 in serum and BALF were significantly higher in group B than in group A (P <0.01), in group C (P <0.01), and in group D (P <0.01). Conclusions The SARS-CoV N protein is pathogenic and can cause lung inflammation and / or acute lung injury in rats. The lung injury is related to the increase and imbalance of proinflammatory cytokines and anti-inflammatory cytokines. The hormones Effectively reduce lung inflammation caused by SARS coronavirus N protein.