[Effect of Radix Astragali on signal transducer and activator of transcription activator-4 and its mRNA expression in a rat model of asthma].
OBJECTIVE
To study the effect of Radix Astragali (RA) on the expression of signal transducer and activator of transcription-4 (STAT4) and its mRNA in the bronchus of a rat model of asthma.


METHODS
Forty male SD rats were randomly divided into four groups: the control group, asthma group, high dosage of RA group and low dosage of RA group. In the experiment, the rat model of asthma was established by the ovalbumin (OVA) challenge methods. The lung tissue was gainedfrom the left lung, bronchoalveolar lavage fluid (BALF) was gained from the right lung. The eosinophils (EOS) numbers and differentiated cell numbers in BALF were counted by different counting fluids; the protein expressions of STAT4 were detected by immunohistochemistry; the mRNA expressions of STAT4 were detected by in situ hybridization.


RESULTS
(1) In the BALF of the asthma group, the absolute numbers of EOS, the ratios of EOS to the total cell numbers (EOS%) of asthma group [(35.81 +/- 7.30) x 10(7)/L, (8. 20 +/- 1.75)%] were all significantly higher than those of the control group [(1.51 +/- 1.04) x 10(7)/L, (0.70 +/- 0.48)%] (P < 0.01); the total cell numbers in BALF, the absolute numbers of EOS and EOS% of RA groups [(14.89 +/- 2.35) x 10(7)/L, (4.70 +/- 0.82)%; (10.98 +/- 1.81) x 10(7)/L, (3.56 +/- 0.53)%] were all significantly lower than those of asthma group (P < 0.01); (2) The concentration of IL-4 in BALF of asthma group (25.70 +/- 7.36) was significantly higher than that of the control group (8.55 +/- 2.97) (P < 0.01); the concentration of IL-4 of BALF of RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly lower than that of asthma group (P < 0.01); the concentration of IL-12 of BALF of asthma group (16.10 +/- 3.38) was significantly lower than that of the control group (42.33 +/- 9.66) (P < 0.01); the concentration of IL-12 of BALF of the RA groups [(31.89 +/- 5.46), (35.26 +/- 6.03)] was significantly higher than that of the asthma group (P < 0.01); (3) Immunohistochemistry and in situ hybridization showed that the protein content of STAT4 and the STAT4 mRNA expression around the bronchus of asthma group [(0.096 +/- 0.012), (0.098 +/- 0.011)] were lower than those of the control group [(0.216 +/- 0.034), (0.228 +/- 0.032)], while those of RA groups [(0.176 +/- 0.012), (0.185 +/- 0.023); (0.183 +/- 0.011), (0.201 +/- 0.019)] were all significantly higher than that of the asthma group (P < 0.01), the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells were the chief expression cells; (4) the STAT4 and the STAT4mRNA expression around the bronchus had positive correlation with the concentration of IL-12 in BALF while had negative correlation with the concentration of IL-4, absolute numbers of EOS in BALF.


CONCLUSIONS
RA has an inhibitory effect on airway inflammation cells infiltration such as EOS, it raises the STAT4 protein and its mRNA expression in the airway smooth muscle cells, the pulmonary arterial smooth muscle cells and endothelial cells, and the key mechanism may be that the IL-12 composition is increased.
Li
Chang-Chong
CC
Department of Respiratory Medicine, Yuying Chidren's Hospital Affiliated to Wenzhou Medical College, Wenzhou 325027, China.
Ye
Le-Ping
LP
Su
Miao-Shang
MS
Li
Meng-Rong
MR
Zhang
Hai-Lin
HL
Cai
Xiao-Hong
XH
Dong
Lin
L
Luo
Yun-Chun
YC
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D027883:Astragalus Plant / Q000737:chemistry*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors