[Effects of matrine on airway inflammation and early airway remodeling in asthmatic mice].
OBJECTIVE
To observe the influence of matrine on airway inflammation and early airway remodeling in asthmatic mice.


METHODS
Fifty BALB/c mice were randomly divided into 5 groups: a normal control group (A), an asthmatic group (B), a dexamethasone (DXM) group (C, 2 mg/kg), a high-dose matrine group (D, 50 mg/kg) and a low-dose matrine group (E, 25 mg/kg). The mice model of asthma in the B, C, D, and E groups was established by ovalbumin (OVA) intraperitoneal injections and aerosolization. Intra-gastric administration of different medications in C, D, E groups and 0.9% sodium chloride in B group were carried out 1 hour before provocation. 0.9% sodium chloride was used for intraperitoneal injection, aerosolization and intra-gastric administration in group A. The lung tissue slices were stained, and then the grade of inflammation around the wall of bronchi, mucous secretion, and the percentage of goblet-cells were counted. The areas of bronchial smooth muscle and of collagen deposition in airway wall were analyzed. The transcriptions and protein expressions of transforming growth factor-beta(1) (TGF-beta(1)) and connective tissue growth factor (CTGF) were measured respectively by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry.


RESULTS
In the A, B, C, D, E groups, the grades of inflammation were 1.5 (1, 2), 4 (4, 5), 2 (1, 3), 2 (2, 3), 3 (2, 3.3), respectively; the degrees of mucous secretions were 1.5 (1, 2), 5 (4, 6), 2 (1, 3), 2 (2.5, 4), 3 (3, 4), respectively. These airway inflammatory parameters in group B were significantly higher than in group A (chi(2) = 21.3, 22.6, P all < 0.01), while they were remarkably decreased in group C compared to group B (chi(2) = 13.3, 15.0, P all < 0.01). These parameters in group D and group E were also lower than those in group B (chi(2) = 9.1, 10.9; 9.8, 9.7; P all < 0.05). The percentage of goblet cells in airway epithelium was (1.7 +/- 0.5)%, (54.7 +/- 15.5)%, (20.4 +/- 5.9)%, (31.7 +/- 7.6)% and (36.2 +/- 10.8)%, respectively; it was significantly higher in group B than in group A (t = 12.0, P < 0.01), and remarkably lower in groups C and D than in group B (t = 7.7, 5.1, P all < 0.01), and lower in group E than in B group (t = 4.2, P < 0.05). In these 5 groups, the area of bronchial smooth muscle was (11.5 +/- 2.1) microm(2)/microm, (30.0 +/- 3.3) microm(2)/microm, (15.2 +/- 3.1) microm(2)/microm, (22.2 +/- 4.8) microm(2)/microm and (26.5 +/- 3.4) microm(2)/microm, respectively; it was significantly higher in group B than in group A (t = 11.4, P < 0.01), and remarkably lower in groups C, D and E than in group B (t = 9.1, 4.7, 2.2, P all < 0.01). The area of collagen deposition was (3.9 +/- 1.8) microm(2)/microm, (24.4 +/- 6.1) microm(2)/microm, (15.4 +/- 3.5) microm(2)/microm, (16.6 +/- 6.0) microm(2)/microm and (17.5 +/- 4.4) microm(2)/microm, respectively; it was also significantly higher in group B than in group A (t = 9.3, P < 0.01), and remarkably lower in groups C and D than in group B (t = 4.1, 3.5, P all < 0.01), and lower in group E than in B group (t = 3.2, P < 0.05). The mRNA levels of TGF-beta(1) were 160 +/- 25, 247 +/- 37, 174 +/- 23, 195 +/- 25 and 207 +/- 42, respectively, and those of CTGF were 86 +/- 8, 160 +/- 24, 94 +/- 10, 93 +/- 14 and 104 +/- 10, respectively in the 5 groups. The levels were remarkably increased in group B, as compared to group A (t = 6.1, 11.6, P all < 0.01), and the levels in groups C, D and E were remarkably decreased, as compared to group B, the difference being significant (t = 3.7, 2.7, 5.1; 10.6, 8.6, 10.3; P all < 0.01). The protein level of TGF-beta(1) in lung tissues was 21 +/- 5, 36 +/- 8, 26 +/- 5, 26 +/- 5 and 26 +/- 5, respectively, and that of CTGF was 15 +/- 4, 27 +/- 5, 21 +/- 4, 22 +/- 3 and 23 +/- 4, respectively in the 5 groups. The levels in B group were significantly increased, as compared to group A (t = 5.7, 6.4, P all < 0.01), and those in groups C and D were significantly decreased (t = 3.9, 3.9; 3.2, 2.8, P all < 0.01), and that in group E was also lower (t = 3.8, 2.5, P all < 0.05), as compared to group B. In all the groups, the protein levels of TGF-beta(1) and CTGF were positively correlated with the area of bronchial smooth muscle and with the area of collagen deposition (r = 0.435, 0.583, 0.522, 0.590, P all < 0.01).


CONCLUSIONS
Matrine inhibited airway inflammation and early airway remodeling in asthmatic mice. The signal transduction of TGF-beta(1) and CTGF maybe involved.
Lei
Ze-Lin
ZL
Department of Gerontal Respiratory Medicine, the First Hospital of Lanzhou University, Lanzhou 730000, China.
Liu
Xiao-Ju
XJ
Ma
Jian-Xiu
JX
Zhu
Jun
J
D056151:Airway Remodeling / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D011807:Quinolizines; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone; D000093842:Matrines