Splenic fibrosis markers in rats with portal vein stenosis.

INTRODUCTION

Congestive splenomegaly (SM)secondary to portal hypertension refers to pathologicalsplenic enlargementcaused byelevatedportal venous pressure; however, the molecular mechanisms underlying splenic fibrosis remain incompletely understood.

MATERIALS: AND:

METHODS

This study established a portal vein stenosis-induced model of SM in Sprague-Dawley rats (SM group, n = 20), with a sham-operated control (SO) group (n = 20). Splenic tissue fibrosis was evaluated using special staining techniques, including Masson's trichrome, Elastica van Gieson, and ammoniacal silver staining. Matrix metallopeptidase 2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, transforming growth factor beta 1 (TGF-β1), and mothers against decapentaplegic homolog 7 (Smad7) were assessed using immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting.

RESULTS

In the SM group, microscopic examination revealed diffuse collagen proliferation, elastic fiber fragmentation, and reticular fiber densification. The proportions of MMP-2-, MMP-9-, TIMP-1-, TIMP-2-, TGF-β1-, and Smad7-positive cells were significantly higher than those in the SO group (p < 0.001). The mRNA expression levels of MMP-2, MMP-9, TIMP-1, TIMP-2, TGF-β1, and Smad7 were also significantly higher than in the SO group (p < 0.001). Protein expression levels of MMP-2, MMP-9, and Smad7 were significantly higher in the SM group than in the SO group (p < 0.001).

CONCLUSIONS

In a rat model of portal hypertension, our findings suggest that MMP/TIMP imbalance and TGF-β1-Smad7 signaling are involved in splenic fibrosis, highlighting the TGF-β1/Smad7 axis as a potential therapeutic target for attenuating splenic fibrotic remodeling.