补肾益气药调节哮喘大鼠下丘脑-垂体-肾上腺轴及白细胞介素-6功能紊乱的实验研究

Regulatory Function of Shen-reinforcing and Qi-supplementing Drugs on Hypothalamic-pituitary-adrenal Axis and Interleukin-6 Dysfunction in Asthmatic Rats

目的观察补肾益气药对支气管哮喘(以下简称哮喘)大鼠模型神经内分泌免疫(neuro-endo-crine-immune,NEI)网络若干组分的影响。方法取健康清洁级雄性挪威(Brown Norway,BN)大鼠40只,大鼠按随机数字表法分为对照组、哮喘模型组、复方低剂量组(0·25g/mL)、复方中剂量组(0·5g/mL)和复方高剂量组(0·75g/mL),以卵白蛋白(OVA)致敏并长期吸入激发制备大鼠反复发作哮喘模型。采用放射免疫法测定血浆中促肾上腺皮质激素(ACTH)含量;采用酶联免疫吸附试验(ELISA)方法检测血清中白细胞介素-6(IL-6)、皮质酮(CORT)水平;采用实时定量-聚合酶链反应(Realtime-PCR)法测定下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达水平。结果哮喘模型组病理学显示呈嗜酸性粒细胞性炎症。哮喘反复发作时,大鼠下丘脑—垂体—肾上腺(hypothalamic-pituitary-adrenal,HPA)轴多水平紊乱,补肾益气药可使ACTH、下丘脑CRHmRNA水平明显升高,与哮喘模型组比较差异有统计学意义(P<0·05);CORT有升高倾向;哮喘时IL-6升高,且与ACTH呈显著负相关(r=-0·325,P=0·043),而用补肾益气药治疗后IL-6水平有所下降。结论补肾益气药可以改善大鼠HPA轴功能,这种作用不依赖IL-6,提示补肾益气药的上述作用靶点在神经内分泌轴,可能是下丘脑。

Objective To evaluate the effect of Shen-reinforcing and qi-supplementing （SRQS） drugs onsome ents of neuro-endoerine-immune （NEI） network in asthma rat model. Methods Asthma model was established by ovalbumin sensitization and long-term excitation. Forty healthy Brown Norway rats of clean grade were randomly divided into 4 groups by randomized digital table, the normal control group and the three treated groups treated by low, moderate and high dose of SRQS drugs respectively. Blood content of adrenocorticotrophie hormone （ACTH） was detected by RIA; interleukin-6 （IL-6） and corticosterone were determined by ELISA; and the mRNA expresion of corticosteroid release hormone （CRH） in hypothalamus was tested by Reahime-PCR. Restilts Eosinophile inflammation was shown in the pathology of asthma model rats, and also shown a multiple level hypothalamie-pituitary-adrenal axis （HPA axis） disorder at the repeated attack of asthma. After treatment, levels of ACTH and CRH mRNA expression in the treated groups were significantly higher than those in the control group （P 〈 0. 05 ）, but the eortieosterone only showed a rising tendency. Level of IL-6 increased during the episode, showing a significant negative correlation with ACTH （ r = - 0. 325, P = 0. 043 ）, and had somewhat reduction after SRQS treatment. Conclusion SRQS drugs could improve the function of HPH axis independent of IL-6, suggesting that the action is possibly targeted on the neuro-endocrine axis, which might be the hypothalamus.