Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of
hepatic cirrhosis and its complications such as gastrointestinal injury and
hepatic encephalopathy. To date, there is no cure for
cirrhosis-associated intestinal mucosal lesion and
ulcer. This study aimed to investigate the effect of
oxymatrine on intestinal epithelial barrier function and the underlying mechanism in
carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received
oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5%
glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and
protein expression levels of
tumor necrosis factor-α (TNF-α) and
interleukin 6 (IL-6) in ileal tissues were analyzed by
reverse-transcriptase polymerase chain reaction (RT-PCR) and
enzyme-linked
immunosorbent assay (ELISA), respectively. Additionally, plasma
endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed.
Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover,
oxymatrine reduced the
protein expression level of NF-κB p65, TNF-α, and
IL-6, which were elevated in the vehicle-treated group. In addition, the serum
endotoxin level was significantly decreased after
oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that
oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for
cirrhosis-associated intestinal mucosal damage.