Effect of ligustrazine on Gas/cAMP/PKA signal activity and airway inflammation in asthmatic rats / 中国药理学通报

Aim To investigate the effect of ligus- trazine on G-protein coupled receptor signal activity in ovalbumin ( OVA)-sensitized and challenged asthmatic rats.Methods This study replicated an OVA-in¬duced juvenile asthmatic rat model, and investigated the effect of ligustrazine on airway hyperresponsive- ness, airway inflammation, lung histopathology, IL-4, IL-5 , 1L-13 , TNF-cx levels in serum, cAMP concentra¬tion in plasma, CREB, PKA, Gas and GRK2 expres¬sion in lung tissues.Results It was showed that the resistance of lung (RL) in asthmatic rats increased, while the pulmonary dynamic compliance ( Cdvn) sig¬nificantly decreased ( P < 0.05 ) compared with the control rats, and the lung tissue injury was serious; the levels of IL-4, IL-5, IL-13, and TNF-cx in serum were significantly increased ( P <0.01 ).The cAMP level in plasma was reduced and the CREB and PKA expres¬ sions were down-regulated significantly ( P < 0.05 ).The Gas expression in lung in asthmatic rats was down- regulated while the GRK2 expression was up-regulated ( P <0.01 ).Ligustrazine coulrl improve the lung inju¬ry and lung function of asthmatic rats, decrease RL and increase Cdvn ( P < 0.05 ) , decrease the levels of 1L-4, 1L-5, 1L-13, and TNF-a in serum (P <0.01) , increase cAMP in plasma and up-regulate the PKA and CREB expression, down-regulate the GRK2 expression and up-regulate the Gas expression significantly ( P < 0.01).Conclusions The above study shows that li¬gustrazine can reduce the AHR, inhibit the inflamma¬tion in asthma, and the up-regulating of Gas/cAMP/ PKA signal activity may be its mechanism.

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

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.

The application of RNA-seq in neurodegenerative diseases / 医学研究生学报

As a noval approach,RNA sequencing(RNA-seq)has been used for studying many diseases in recent years,es-pecially with the introduction of next generation sequencing(NGS),much more and more attention has been gathered on the utilization of RNA-seq for research purpose of central nervous system(CNS). This review focuses on applying of RNA-seq in central nervous sys-tem,taking neurodegenerative diseases for example,including Alzheimer's disease,Parkinson's disease and Huntington's disease,to expound the application of RNA-seq in the studying of central nervous system diseases and the prospective side of finding potential tar-gets in drug treatment of neurodegenerative diseases.