[A study of pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and effects of glucocorticoids on it].
OBJECTIVE
To study the pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and the effects of glucocorticoids on the inflammatory reaction.


METHODS
The pulmonary inflammatory reaction in rat models were induced by intratracheal instillation of N-protein of SARS-CoV with a dose of 0.2 mg/kg. The rats were randomly divided into four groups: normal saline control group (Nc group), N-protein group 1 (P1 group, 6 h), N-protein group 2 (P2 group, 24 h), and N-protein + dexamethasone group (P + D group, dexamethasone 10 mg/kg intraperitoneally). The blood samples, bronchial alveolar lavage fluid (BALF) and lung tissue were collected after challenge. The cytological and histopathologic changes of lung tissues were observed and the wet/dry ratios (W/D) of lung tissue were determined. The interleukin (IL)-6, IL-10 and transforming growth factor-beta1 (TGF-beta1) of serum and BALF were measured by ELISA.


RESULTS
(1) Compared with the percentage of peripheral blood lymphocytes in Nc group [(68.42 +/- 13.07)%], that in P2 group [(50.50 +/- 14.36)%] was significantly decreased (P < 0.05); compared with Nc group and P2 group, that in P + D group was furthermore significantly decreased (P < 0.01). Compared with the total WBC of peripheral blood in Nc group [(5.86 +/- 2.25) x 10(9)] and P2 group [(4.83 +/- 1.49) x 10(9)], that in P + D group [(1.96 +/- 1.30) x 10(9)] was significantly decreased (P < 0.01). (2) Compared with the total WBC of BALF in Nc group [(95 +/- 29) x 10(7)], that in P2 group [(160 +/- 60) x 10(7)] was significantly increased (P < 0.05); but compared with P2 group, that in P + D group [(62 +/- 23) x 10(7)] was significantly decreased (P < 0.05). Analysis of BALF differential cell counts showed that the majority of cells were alveolar macrophages in all groups. (3) The W/D ratios of lung tissue in both P1 and P2 group [(5.18 +/- 0.29) and (5.19 +/- 0.34), respectively] after N-protein challenge were significantly increased than that in Nc groups [(4.77 +/- 0.27), P < 0.05]; the W/D ratio in P + D group (4.70 +/- 0.18) was significantly decreased than that in P2 group (P < 0.01). (4) Compared with Nc group, the levels of IL-6, IL-10, TGF-beta1 in both serum and BALF of P1 group were significantly increased (P < 0.01), and the levels of these cytokines in P2 group were significantly higher than those in P1 group (P < 0.01), but significantly lower in P + D group compared with P2 group (P < 0.01).


CONCLUSIONS
The N-protein of SARS-CoV had pathogenicity and could induce obvious pulmonary inflammatory reaction and acute lung injury, which were related to the increase and imbalance of pro-inflammatory and anti-inflammatory cytokines. Glucocorticoids could effectively alleviate the pulmonary inflammatory reaction induced by N-protein of SARS-CoV.
Hao
Dong
D
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
He
Li-xian
LX
Qu
Jie-ming
JM
Pan
Jue
J
Hu
Bi-jie
BJ
Zhang
Jing
J
Li
Zhuo-zhe
ZZ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D000086462:Coronavirus Nucleocapsid Proteins; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008297:Male; D019590:Nucleocapsid Proteins / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
D000086462:Coronavirus Nucleocapsid Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D019590:Nucleocapsid Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D003907:Dexamethasone