Anti-Inflammatory Combinations Targeting Oncostatin M Gene to Remodel Intestinal Flora and Alleviate Inflammation of Perianal Ulcer in Rats.

BACKGROUND: Perianal Abscess is an inflammatory disease caused by infection in the perianal area, characterized by inflammatory cell infiltration and imbalance of intestinal flora. The herbal medicine anti-inflammatory combination (KYHJ) has therapeutic effects in acute and chronic soft tissue infections, but the specific therapeutic mechanism in perianal inflammatory diseases is unclear. There is a literature evidence showing the role of OSM gene in inflammatory conditions, however this was not previously studied in perianal abscess. METHODS: A perianal inflammation model was constructed in SD rats using 75% glacial acetic acid and treated with different doses of KYHJ; genome-wide changes were detected by RNA sequencing. H&E staining observed pathological states, TUNEL kit detected apoptosis, WB measured apoptotic protein levels, ELISA detected inflammatory factors in serum, and 16S rRNA sequencing analyzed intestinal flora abundance. In vitro, an anal epithelial cell inflammation model induced by LPS was treated with 10% KYHJ-containing serum; EDU assay, flow cytometry, WB, and ELISA were used to detect cell proliferation, apoptosis, related protein levels, and inflammatory factor secretion. Oncostatin M gene was knocked down in rats and overexpressed in epithelial cells for mechanism exploration. RESULTS: Results showed that KYHJ ameliorated perianal tissue inflammatory infection, inhibited apoptosis, and restored intestinal flora abundance. Initial transcriptome analysis, RT-qPCR and WB performed in this study have additionally supported the role of OSM gene. RNA sequencing linked the tested anti-inflammatory effects of KYHJ to reduced Oncostatin M (OSM) gene expression. RNA transcriptome sequencing showed high Oncostatin M expression in inflamed rats and low expression in the KYHJ group; in vivo knockdown improved perianal inflammation and increased flora abundance. In vitro, KYHJ - containing serum inhibited LPS - induced apoptosis, promoted proliferation, and reduced inflammatory factor secretion, which were reversed by Oncostatin M overexpression. CONCLUSION: KYHJ ameliorates perianal inflammatory diseases by targeting Oncostatin M, restoring intestinal flora imbalance, promoting cell proliferation, and inhibiting apoptosis.