[Establishing a model of neutropenia rat with Pseudomonas aeruginosa pneumonia and a study on its inflammatory reaction].
OBJECTIVE
To establish an animal model and study the inflammatory reaction of P. Aeruginosa pneumonia in neutropenia rats. METHODS Fifty SD rats were randomly divided into two groups: drug-treated group and control CON group. Drug-treated group was given a combination regimen of cyclophosphamide (15 m x kg(-1) d(-1)) and cortisone acetate (100 mg x kg(-1) x d(-1)) for seven days,then both groups were intratracheally challenged with P. Aeruginosa (0.2 ml ATCC 27853 6 x 10(8) CFU/ml). Their blood, bronchial alveolar lavage fluid (BALF) and lung tissue were collected before and 3, 6, 9, 24 h after challenging. Cytological and bacteriological examinations were performed, histopathologic changes of lung tissue were observed. Total proteins (TP) of BALF and the wet/dry ratio (W/D) of lung tissue were determined.


RESULTS
(1) Compared with CON group, rats of drug-treated group showed obviously weight loss and thymus atrophy [(141 +/- 8) g] vs [(201 +/- 14) g], [(0.06 +/- 0.05) g] vs (0.40 +/- 0.10) g, P < 0.001], developed leukocytopenia [(0.9 +/- 0.3) x 10(9)/L] vs [(7.3 +/- 1.9) x 10(9)/L, P < 0.001] and the numbers of alveolar macrophage in BALF decreased significantly; (2) After PA challenging, drug-treated rats showed less activities, worse situations and higher mortality (10.8%) than CON group which recovered quickly and none of them died. PA was identified from samples of BALF and lung tissue, both groups developed inflammatory reaction at 6 - 9 h in high level. Pulmonary pathologic study revealed that polymorphonuclears response of drug-treated group was delayed and less serious than that of CON group [at 9 h, drug-treated group, (102 +/- 13)/HP vs CON group (291 +/- 20)/HP, P < 0.01], however, interstitial edema, capillary congestion and focal hemorrhages were more obvious; (3) After PA challenging especially at 6 - 9 h, W/D ratio and TP concentrations were significantly high in both groups than those of before [drug-treated group, W/D (9.2 +/- 1.3) vs (5.9 +/- 1.4) TP (1.59 +/- 0.83) mg/ml vs (0.19 +/- 0.07) mg/ml; CON group:W/D 7.2 +/- 2.5 vs 4.9 +/- 0.8,TP(0.42 +/- 0.16) mg/ml vs (0.13 +/- 0.04) mg/ml, P < 0.05], however the alterations were much greater in drug-treated group (P < 0.05). Alteration of TP concentration showed some correlation with numbers of polymorphonuclears in lung tissue of CON group (r = 0.926, P < 0.05), but not in drug-treated group (r = 0.58, P = 0.31).


CONCLUSIONS
It was indicated that there may be other mechanisms than polymorphonuclears infiltration contributing to the more severe lung injury in drug-treated group characterized as neutropenia.
Li
Z
Z
Department of Pulmonary Medicine, Zhongshan Hospital, Institute of Respiratory Disease, Fudan University, Shanghai 200032, China.
Qu
J
J
He
L
L
D000818:Animals; D004195:Disease Models, Animal; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000382:microbiology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000473:pathology; D011552:Pseudomonas Infections / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D051381:Rats; D017207:Rats, Sprague-Dawley