Effect of Jianpi Bufei Prescription on cAMP/PKA/CREB Signaling Pathway in Juvenile Asthma Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of Jianpi Bufei prescription （JPBFP） on airway inflammation， airway hyperresponsiveness （AHR）， and cyclic adenosine monophosphate （cAMP） signaling pathway activity in ovalbumin （OVA）-sensitized and challenged juvenile asthma rats. Method:Seventy-five male SD rats were randomly divided into a blank group （<italic>n</italic>=15） and an experimental group （<italic>n</italic>=60）. The rats in the experimental group were sensitized by aluminum hydroxide gel containing 0.2% OVA and stimulated by aerosol inhalation of normal saline containing 1% OVA to induce an asthma model， followed by assignment into the following groups： a model group （<italic>n</italic>=15）， a JPBFP group （<italic>n</italic>=15， 8.37 g·kg^-1·d^-1）， an aminophylline group （<italic>n</italic>=15， 40 mg·kg^-1·d^-1）， and a dexamethasone group （<italic>n</italic>=15， 0.1 mg·kg^-1·d^-1）. AHR was detected by the pulmonary function analyzer， changes in inflammatory cells by white blood cell （WBC） count and differential blood count in bronchoalveolar lavage fluid （BALF）， and pathological changes of lung tissues by hematoxylin-eosin （HE）， Masson， and periodic acid-schiff （PAS） staining. The interleukin （IL）-4， IL-5， IL-13， interferon （IFN）-<italic>γ</italic>， and tumor necrosis factor （TNF）-<italic>α</italic> levels in serum and the cAMP level in plasma were tested by the enzyme-linked immunosorbent assay （ELISA）. Protein kinase A （PKA） expression in lung tissues was detected by immunohistochemistry. The cAMP-response element-binding protein （CREB） mRNA and protein expression in lung tissues was detected by the real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the blank group， the model group showed increased lung resistance， decreased pulmonary compliance （<italic>P</italic><0.05）， elevated WBC count and proportion of eosinophils in BALF （<italic>P</italic><0.05）， up-regulated levels of IL-4， IL-5， IL-13， and TNF-<italic>α</italic> in peripheral blood， declining IFN-<italic>γ</italic> level （<italic>P</italic><0.01）， severe pathological changes of lung tissues， dwindled cAMP， and down-regulated PKA and CREB expression （<italic>P</italic><0.01）. Compared with the model group， JPBFP inhibited AHR， reduced WBC count and proportion of eosinophils in BALF and lung resistance （<italic>P</italic><0.05）， improved pathological changes of lung tissues， increased pulmonary compliance， and up-regulated cAMP in serum and PKA and CREB expression in lung tissues （<italic>P</italic><0.01）. Conclusion:JPBFP can improve AHR， inhibit airway inflammation， and alleviate lung injury in asthma rats. Its mechanism may be related to the up-regulation of the activity of the cAMP/PKA/CREB signaling pathway.