Wuhutang Alleviates Respiratory Syncytial Virus-induced Asthma in Mice by Inhibiting STAT3 Protein and Regulating Dendritic Cell Autophagy / 中国实验方剂学杂志

Objective:To investigate the therapeutic mechanism of Wuhutang on respiratory syncytial virus （RSV）-induced asthma in mice and its influence on the expression of signal transducer and activator of transcription 3 （STAT3） in lung tissue. Method:One hundred female BALB/c mice of SPF grade were randomly divided into a normal group and an experimental group. After successful modeling via aerosol inhalation of RSV and ovalbumin （OAV）， the mice in the experimental group were further randomized into the following seven groups： model， positive control （dexamethasone， 1.82 mg·kg^-1）， STAT3 inhibitor （STATTIC， 3.75 mg·kg^-1）， STAT3 inducer （colivelin， 1.0 mg·kg^-1）， and low-， medium-， and high-dose （1.6， 3.2， and 6.4 g·kg^-1， respectively） Wuhutang groups. The corresponding drugs were administered for two weeks， followed by the detection of airway reactivity using a small animal ventilator， the pathological changes in lung tissue， mucus secretion by goblet cells and collagen deposition in airway were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS） and Masson staining， the serum levels of interleukin-6 （IL-6）， IL-10， and IL-17 were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA in lung tissue were detected by fluorescence-based real-time polymerase chain reaction （Real-time PCR）， autophagosomes present in lung tissue were examined by transmission electron microscopy， the protein expression levels of ATG5 and SQSTM1 in dendritic cells （DCs） and STAT3 and p-STAT3 in lung tissue were detected by Western blot. Result:The airway reactivity of the model group was enhanced in contrast to that in the model group （<italic>P<</italic>0.01）， manifested as inflammatory cell infiltration around the lung tissue， excessive metaplasia of goblet cells， and extensive deposition of airway collagen， the expression levels of serum IL-6 and IL-17 were increased （<italic>P<</italic>0.01）， while that of IL-10 declined （<italic>P<</italic>0.01）， the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA were elevated （<italic>P</italic><0.01）， the number of autophagosomes in the lung tissue increased. The protein expression levels of ATG5， STAT3， and p-STAT were up-regulated， while that of SQSTM1 was down-regulated （<italic>P<</italic>0.01）. Compared with the model group， Wuhutang and STATTIC significantly reduced the airway hyperresponsiveness of asthmatic mice （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， alleviated RSV-induced pathological changes in lung tissue， reduced the contents of serum IL-6 and IL-17 （<italic>P<</italic>0.01）， increased serum IL-10 and ATG5 in DCs （<italic>P<</italic>0.01）， down-regulated the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA as well as the protein expression levels of SQSTM1， STAT3 and p-STAT3 （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， and elevated the number of autophagosomes. Conclusion:Wuhutang relieves airway inflammation， improves airway remodeling and reduces airway hyperresponsiveness in RSV-induced asthmatic mice by inhibiting STAT3 protein and up-regulating DC autophagy in lung tissue.