الفهرس 
Possible antifibrotic mechanisms of carvedilol in a rat model of liver fibrosis
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Abstract
Circulating microRNAs (miRNAs) play a role in modulating the prevalence of fibrosis and have been a target of the cardiac anti-fibrotic effect of carvedilol. However, the impact of miRNAs on the hepatoprotective effect of this non-selective Ý-blocker has not been yet elucidated. Hence, the current goal is to evaluate the potential role of circulating miR-200a in the hepatic anti-fibrotic pathway of carvedilol.Male Wistar rats were randomized into normal, CCl4 (2 ml/kg, i.p, twice weekly for 8 weeks), and CCl4+Carvedilol (10mg/kg, p.o, daily). Carvedilol over-expressed the circulating miR-200a to modulate epithelial mesenchymal transition (EMT) markers (vimentin, E-Cadherin). In turn, carvedilol increased SMAD7 gene expression and protein content to attenuate the pro-fibrogenic marker transforming growth factor Ý1 (TGF-Ý1) and the inflammatory markers (p-38 MAPK and p-S536-NF-mB p65).The anti-fibrotic potential was reflected on the decreased expression of the mesenchymal product and EMT marker Ü-SMA, besides the improved histopathological examination, and the fibrosis scores/collagen quantification to enhance liver functions (AST, ALT, ALP, and AST/ platelet ratio index; APRI). In conclusion, circulating miR-200a/SMAD7/ TGF-Ý1/EMT/ MAPK axis is crucial in the hepatic anti-fibrotic mechanism of carvedilol