Li Chang-Chong, Ye Le-Ping, Su Miao-Shang, Li Meng-Rong, Zhang Hai-Lin, Cai Xiao-Hong, Dong Lin, Luo Yun-Chun
Department of Respiratory Medicine, Yuying Chidren's Hospital Affiliated to Wenzhou Medical College, Wenzhou 325027, China.
Zhonghua Er Ke Za Zhi. 2007 Oct;45(10):727-31.
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.
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.
(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.
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.
研究黄芪对哮喘大鼠模型支气管中信号转导及转录激活因子4（STAT4）及其mRNA表达的影响。
将40只雄性SD大鼠随机分为四组：对照组、哮喘组、黄芪高剂量组和黄芪低剂量组。实验中，采用卵清蛋白（OVA）激发法建立大鼠哮喘模型。取左肺组织，右肺获取支气管肺泡灌洗液（BALF）。用不同计数液计数BALF中嗜酸性粒细胞（EOS）数量及分化细胞数量；采用免疫组织化学法检测STAT4蛋白表达；采用原位杂交法检测STAT4 mRNA表达。
（1）哮喘组BALF中EOS绝对数、EOS占总细胞数的比例（EOS%）[（35.81±7.30）×10⁷/L，（8.20±1.75）%]均显著高于对照组[（1.51±1.04）×10⁷/L，（0.70±0.48）%]（P<0.01）；黄芪组BALF中总细胞数、EOS绝对数及EOS%[（14.89±2.35）×10⁷/L，（4.70±0.82）%；（10.98±1.81）×10⁷/L，（3.56±0.53）%]均显著低于哮喘组（P<0.01）；（2）哮喘组BALF中IL-4浓度（25.70±7.36）显著高于对照组（8.55±2.97）（P<0.01）；黄芪组BALF中IL-4浓度[（31.89±5.46），（35.26±6.03）]显著低于哮喘组（P<0.01）；哮喘组BALF中IL-12浓度（16.10±3.38）显著低于对照组（42.33±9.66）（P<0.01）；黄芪组BALF中IL-12浓度[（31.89±5.46），（35.26±6.03）]显著高于哮喘组（P<0.01）；（3）免疫组织化学和原位杂交显示，哮喘组支气管周围STAT4蛋白含量及STAT4 mRNA表达[（0.096±0.012），（0.098±0.011）]低于对照组[（0.216±0.034），（0.228±0.032）]，而黄芪组[（0.176±0.012），（0.185±0.023）；（0.183±0.011），（0.201±0.019）]均显著高于哮喘组（P<0.01），气道平滑肌细胞、肺动脉平滑肌细胞及内皮细胞为主要表达细胞；（4）支气管周围STAT4及STAT4 mRNA表达与BALF中IL-12浓度呈正相关，与IL-4浓度、BALF中EOS绝对数呈负相关。
黄芪对EOS等气道炎症细胞浸润有抑制作用，可提高气道平滑肌细胞、肺动脉平滑肌细胞及内皮细胞中STAT4蛋白及其mRNA表达，关键机制可能是IL-12成分增加。
