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.
Alcoholic liver disease (ALD) is an important worldwide public health issue with no satisfying treatment available since now. Here we explore the effects of recombinant human cytoglobin (rhCygb) on chronic alcohol-induced liver injury and the underlying mechanisms. In vivo studies showed that rhCygb was able to ameliorate alcohol-induced liver injury, significantly reversed increased serum index (ALT, AST, TG, TC and LDL-C) and decreased serum HDL-C. Histopathology observation of the liver of rats treated with rhCygb confirmed the biochemical data. Furthermore, rhCygb significantly inhibited Kupffer cells (KCs) proliferation and TNF-α expression in LPS-induced KCs. rhCygb also inhibited LPS-induced NADPH oxidase activity and ROS, NO and O2•− generation. These results collectively indicate that rhCygb exert the protective effect on chronic alcohol-induced liver injury through suppression of KC activation and oxidative stress. In view of its anti-oxidative stress and anti-inflammatory features, rhCygb might be a promising candidate for development as a therapeutic agent against ALD.
Backgroud
The regenerative capacity of the liver is crucial for the host to survive after serious hepatic injuries, tumor resection, or living donor liver transplantation.
Panax notoginseng
saponins (PNS) have been reported to exert protective effects during organ injuries. The present study aimed to evaluate the effect of PNS on liver regeneration(LR) and on injuries induced by partial hepatectomy (PH).
Methods
We performed 70% partial PH on C57BL/6 J mice treated with or without PNS. LR was estimated by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were analyzed by Western blot.
Results
Different concentrations of PNS promoted hepatocyte proliferation in vitro. Mice in the PNS group showed higher liver/body weight ratios at 2 d and 7 d (
P
< 0.05) after PH and lower levels of serum ALT and AST (
P
< 0.05) compared to those of mice in the normal control (NC) group. Histological analysis showed that the expression of proliferating cell nuclear antigen(PCNA) at 2 d and 7 d after PH was significantly higher in the PNS group than in the NC group (
P
< 0.05). Mechanistically, the AKT/mTOR cell proliferation pathway and AKT/Bad cell survival pathway were activated by PNS, which accelerated hepatocyte proliferation and inhibited apoptosis (
P
< 0.05).
Conclusions
PNS promoted liver regeneration through activation of PI3K/AKT/mTOR and upregulated the AKT/Bad cell pathways in mice.
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