[Effect of peroxisome proliferators activated receptor gamma and its ligand on airway mucus hypersecretion in rats].
OBJECTIVE
To explore the effect and the molecular mechanisms of peroxisome proliferators activated receptor gamma (PPAR-gamma) and its ligand on airway mucus hypersecretion.


METHODS
Thirty-six Sprague-Dawley rats were randomized into the following groups: (1) Rats in the saline control group (n = 6) received normal saline inhalation; (2) Rats in the rosiglitazone control group (n = 6) received inhaled saline and oral rosiglitazone 8 mg/kg simultaneously; (3) Rats in the acrolein group (n = 6) received inhaled acronine 3.0 mg/L, 6 h/day, for 12 days; (4) Rats in the rosiglitazone intervention group (n = 18) received inhaled acrolein and oral rosiglitazone 2 mg/kg, 4 mg/kg, 8 mg/kg, respectively, as the low dose, the moderate dose and the high dose intervention groups (n = 6 each). The lung tissue sections were stained with HE for histopathological examination. The changes of airway mucus were examined with AB-PAS. Expressions of MUC5AC and PPAR-gamma protein in the bronchial epithelium were detected by immunohistochemistry. The expression of mRNA was measured with real time RT-PCR. The data were analyzed with SPSS 10.0 software. Variables were compared with One-Way ANOVA and q test. The correlations between variables were analyzed using Pearson's correlation coefficient.


RESULTS
The levels of airway mucus were (60.2 +/- 9.3)%, (4.9 +/- 1.0)%, (53.3 +/- 8.5)%, (26.5 +/- 7.4)%, (12.5 +/- 3.7)% respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 93.80, P < 0.01). The protein expressions of MUC5AC in the bronchial epithelium examined by immunohistochemistry were 4339 +/- 453, 1636 +/- 282, 3996 +/- 346, 3048 +/- 331, 2376 +/- 343 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 67.74, P < 0.01). The protein expressions of PPAR-gamma were 1159 +/- 184, 838 +/- 151, 1272 +/- 189, 1568 +/- 282, 1872 +/- 270 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 21.53, P < 0.01). The mRNA expressions of MUC5AC (the relative copies) were 35.3 +/- 10.0, 2.2 +/- 0.7, 30.5 +/- 10.2, 18.6 +/- 5.3, 10.8 +/- 2.6 respectively in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 29.67, P < 0.01). The mRNA expressions of PPAR-gamma (the relative copies) were 7.8 +/- 1.9, 2.0 +/- 0.6, 9.8 +/- 2.8, 18.6 +/- 5.3, 31.6 +/- 8.9 in the acrolein group, the saline control group, the low dose rosiglitazone intervention group, the moderate dose rosiglitazone intervention group, and the high dose rosiglitazone intervention group, the difference being significant among groups (F = 39.47, P < 0.01). The expression of MUC5AC mRNA was negatively correlated with the protein expression of PPAR-gamma in the acrolein group (r = -0.880, P < 0.01).


CONCLUSIONS
PPAR-gamma was involved in airway mucus hypersecretion induced by acrolein. PPAR-gamma and its ligand rosiglitazone inhibited acrolein-induced airway mucus hypersecretion, possibly through downregulation of MUC5AC.
Liu
Wei-Jia
WJ
Department of Respiratory Medicine, Sichuan University West China Hospital, Chengdu 610041, China.
Li
Wan-Cheng
WC
Xu
Zhi-Bo
ZB
Feng
Yu-Lin
YL
D000818:Animals; D008024:Ligands; D008297:Male; D055271:Mucin 5AC / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D008024:Ligands; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone