RESUMO
This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8 g/kg/d), and montelukast sodium treatment (MAS) group (1 mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with Allobaculum but inversely correlated with unclassified_f_Oscillospiraceae; propanoic acid was positively associated with Lactobacilli but negatively associated with Romboutsia; butanoic acid exhibited positive correlations with Akkermansia and Lactobacilli, but negative correlations with unclassified_f_Oscillospiraceae, Eubacterium_xylanophilum_group, and Lachnospiraceae_NK4A136_group; Additionally, TNF-α was inversely linked to Allobaculum, while IL-8 was positively related to Romboutsia and Turicibacter. In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.
RESUMO
This study aimed to determine the effects of Xiebai Zengye decoction (XBZY) on airway inflammation and respiratory function in rats with postinfectious cough (PIC), and its regulatory effects on the extracellular signal-regulated kinase (ERK) signaling pathway. Compared with the normal group, the rats from the PIC group had significantly shortened expiratory time (TE) and enhanced pause (EEP), increased resistance (RT), and enhanced pause (Penh), along with increased levels of serum interleukin-4 (IL-4) and IL-6, and decreased levels of IL-10. The lung and colon tissues of rats from the PIC group showed histopathological changes, including inflammatory cell infiltration, damaged mucosal epithelium, and crypt structure, with significantly increased ERK mRNA and protein expression levels. Treatment with XBZY and montelukast sodium (MAS) improved the respiratory function and serum cytokine levels, reduced tissue inflammation, and decreased ERK mRNA and protein expression levels in the lung and colon tissues. In the lung tissues, XBZY treatment significantly decreased the expression of phosphorylated-ERK (p-ERK) protein, as well as p-MEK1/2, p-ERK1/2, and p-c-Fos proteins, while in the colon tissues, XBZY significantly decreased the expression of p-ERK1/2 and p-c-Fos proteins. However, MAS treatment only showed significant improvement in the lung tissue inflammation score, and the expression level of p-ERK protein in the lung tissue was decreased. In conclusion, the present study suggests that XBZY has a potential therapeutic effect on PIC by improving respiratory function and attenuating inflammation, and this effect may be associated with the inhibition of the ERK signaling pathway. These findings could provide a new direction for the development of treatments for PIC. However, further research is needed to elucidate the underlying molecular mechanisms of XBZY and to confirm its safety and efficacy in clinical trials.
Assuntos
Tosse , MAP Quinases Reguladas por Sinal Extracelular , Ratos , Animais , Tosse/tratamento farmacológico , Proteínas Proto-Oncogênicas c-fos/farmacologia , Sistema de Sinalização das MAP Quinases , Transdução de Sinais , Inflamação/tratamento farmacológico , RNA MensageiroRESUMO
BACKGROUND: TGFB-induced factor homeobox 2 (TGIF2) has been reported to exert essential functions in brain development. This study aimed to elucidate the correlation of TGIF2 with autism, a neurodevelopmental condition which presents with severe communication problems. METHODS: An autism-related gene expression dataset GSE36315 was used to analyze aberrantly expressed genes in autistic brain tissues. Maternal mice were treated with valproate (VPA), and their offspring were selected as model mice with autism. The functions of TGIF2 in autism-like symptoms in mice were examined by behavioral tests and histological examination of their hippocampal tissues. Mouse hippocampal neurons were extracted for in vitro studies. A gene set enrichment analysis was performed to analyze the signaling pathways involved, and the upstream factors influencing TGIF2 expression were explored in the ENCODE database and validated by ChIP-qPCR assays. RESULTS: TGIF2 was poorly expressed in autistic patients in the GSE36315 dataset as well as in the temporal cortex tissues of autistic mice. Adenovirus-mediated overexpression of TGIF2 suppressed autism-like symptoms and neuronal apoptosis in autistic mice. TGIF2 activated the Wnt/ß-catenin signaling pathway. TGIF2 could be regulated by monomethylation of histone H3 Lys4 (H3K4me1). The histone demethylase LSD1 was highly expressed in the tissues of autistic mice and bound to TGIF2 promoter, which was possibly responsible for TGIF2 downregulation. CONCLUSION: This research suggests that the downregulation of TGIF2, possibly regulated by LSD1/H3K4me1, is correlated with neuronal apoptosis and development of autism in mice through the inactivation of the Wnt/ß-catenin pathway.