Changes in the apoptotic index, along with gene and protein expression levels, in splenomegaly due to portal vein stenosis in rats.

BACKGROUND

The spleen is an important peripheral immune organ, and splenomegaly (SM) is a common complication of portal hypertension. However, the regulatory mechanisms underlying splenic apoptosis remain poorly understood.

MATERIALS AND

METHODS

A portal vein stenosis-induced SM model was established in Sprague-Dawley rats, using a sham-operated (SO) group as the control. Apoptotic changes in splenic tissue cells were evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry staining, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and western blot analysis.

RESULTS

Compared with the SO group, the SM group had a significantly higher proportion of apoptotic cells and higher mRNA expression levels of the pro-apoptotic Bax, caspase-3, and caspase-9 genes, whereas the proportion of apoptotic cells and mRNA expression levels of anti-apoptotic Bcl-2 were significantly lower in the SM group. The protein expression levels of pro-apoptotic Bax, caspase-3, and caspase-9 were significantly increased in the SM group compared with the SO group. Transmission electron microscopy imaging revealed that macrophages of rats with SM had swollen mitochondria, marginated chromatin, and pyknotic nuclei.

CONCLUSION

In rat SM, the concurrent activation of pro-apoptotic pathways and anti-apoptotic pathways leads to increased cell apoptosis. This suggests that an imbalance in the Bax/Bcl-2 ratio promotes apoptosis through the mitochondrial pathway.