Inhibitory effect of flufenidone on TGF-β1/Smads pathway in hepatocytes of rats with diethylnitrosamine (DEN)-induced liver injury / 中国临床药理学与治疗学
Chinese Journal of Clinical Pharmacology and Therapeutics
; (12): 739-746, 2022.
Article
Dans Zh
| WPRIM
| ID: wpr-1014811
Responsable en Bibliothèque :
WPRO
ABSTRACT
AIM:
To explore the protective effect of fluorofenidone (AKF-PD) on diethylnitrosamine-induced liver injury in rats and its inhibition of the TGF-β1/Smads pathway in hepatocytes.METHODS:
Fifty-five male Sprague Dawley (SD) rats were randomly divided into three groups model group (DEN group, n=20) were gavaged with DEN (10 mg/kg), 5 times for 14 weeks; control group (n=20) were gavaged with saline with the same volume of the model group; treatment group (DEN+AKF-PD Group, n=15), after 4 weeks of modeling, they were gavaged with AKF-PD (500 mg/kg) daily, and stopped at 14 weeks. At the end of experiment, the rats were killed by anesthesia and spinal dislocation. Masson staining was used to observe collagen deposition; primary hepatocytes were extracted and identified, and the levels of α-smooth muscle actin (α-SMA), TGF-β1, Smad3, and Smad7 mRNA, and the expression of Smad3 and Smad7 proteins in hepatocytes were detected.RESULTS:
Compared with the control group, Masson staining showed that collagen deposition increased in the DEN group; AKF-PD treatment could significantly improve liver pathological damage and reduce collagen deposition. In addition, compared with the DEN group, the α-SMA, TGF-β1, and Smad3 mRNA levels of the AKF-PD group were significantly reduced, and the Smad7 mRNA level was increased. Moreover, AKF-PD treatment could dependably reduce the expression of Smad3 and increase Smad7.CONCLUSION:
AKF-PD can significantly improve liver injury and fibrosis in rats caused by DEN. This effect may be related to the down-regulation of α-SMA, TGF-β1, and Smad3 mRNA levels in hepatocytes and the increase of Smad7 mRNA levels.
Texte intégral:
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Indice:
WPRIM
langue:
Zh
Texte intégral:
Chinese Journal of Clinical Pharmacology and Therapeutics
Année:
2022
Type:
Article