Dissertation > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Cirrhosis

The Effects of Propranolol on Proliferation, Apoptosis and Fibrogenesis of Human Hepatic Stellate Cells

Author FengBaoBao
Tutor ZhangChunQing
School Shandong University
Course Clinical
Keywords hepatic stellate cell hepatic fibrosis propranolol cell proliferation apoptosis
CLC R575.2
Type Master's thesis
Year 2011
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Objective:The high incidence and high mortality of liver cirrosis have become worldwide problems. The gastroesophageal variceal bleeding induced by portal hypertension is the leading cause of deaths in patients with liver cirrosis. Propranolol is the first-line drug to prevent gastroesophageal variceal bleeding which needs to be taken for long term with enough doses. However, there is no research on its effects on the activation of hepatic stellate cells and hepatic fibrosis after long-term administration. It needs to be considered that whether propranolol can promote or inhibit liver cirrosis when patients take it for a long time.This study investigates the effects and mechanisms ofβ-adrenoceptor blocker propranolol on human hepatic stellate cells through in vitro observation of propranolol on proliferation, apoptosis and fibrogenesis of cultured HSC-LX2, aiming to explore whether there is any potential stimulatory or inhibitory effects of propranolol on hepatic fibrosis after long-term administration.Methods:HSC-LX2 human hepatic stellate cell line was chosen as the study model of the activated HSC. Hepatic stellate cells were cultured in medium containing different concentrations of propranolol (10μmol·L-1,25μmol·L-1, 50μmol·L-1, 100μmol·L-1), and cells were collected at 24h. The cell growth and proliferation were assessed via water-soluble tetrazolium-1 (WST-1) cell proliferation and cytotoxicity assay kit at different concentrations. The apoptosis of HSC-LX2 cells were detected by fluorescence-activated cell sorting (FACS). The levels of TGF-β1, MMP-2, collagenⅠand collagenⅢreleased from the cultured HSCs were determined by enzyme linked immunosorbent assay (ELISA). The expression of a-SMA was detected by Western blotting. Data were presented as x±s, comparisons among three or more groups were made by one-way ANOVA followed by LSD t test and P<0.05 was considered statistically significant.Results:Propranolol inhibited the proliferation of HSCs, the inhibitory ratio increased from 35.51%(10μmol·L-1) to 95.74%(100μmol·L-1). The apoptosis of propranolol groups(54.97±0.86%,57.17±1.15%,66.30±1.11% and 81.96±1.72%) were higher than that of control group. The expression levels of a-SMA in propranolol groups(0.6771±0.0064,0.6899±0.0185,0.6271±0.0091 and 0.5951±0.0219) were lower than that of control group. Propranolol decreased the release levels of TGF-β1, MMP-2, collagenⅠand collagenⅢmeasured by ELISA, concentration dependently.Conclusions:1.Propranolol inhibited the activation and proliferation of HSCs, concentration dependently. It might play the role through combination with (3-adrenoreceptors.2.Propranolol promoted the apoptosis of HSCs, concentration dependently. It might play the role by combining withβ-adrenoreceptors.3.Propranolol also decreased the secretion of TGF-β1, MMP-2, collagenⅠand collagenⅢ, concentration dependently.These results suggest that propranolol may play a role in reduing hepatic fibrosis and decreasing intrasinusoidal pressure through inhibiting the secretion of ECM in patients with cirrosis after long-term administration.

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