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The Regulatory Effect Of Matrine On Theα-SMA,TGF-β1and PDGF-B In Mice With Hepatic Fibrosis

Posted on:2013-06-22Degree:MasterType:Thesis
Country:ChinaCandidate:Z X YangFull Text:PDF
GTID:2234330371987529Subject:Surgery
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AIM:To observe the therapeutic effects of Matrine on the mice with hepatic fibrosis induced by carbon tetrachloride, and to explore mechanism of anti-fibrosis with Matrine through stutying the impact of Matrine on activation of hepatic stellate cell (HSC) and expression level of transforming growth facters-β1(TGF-β1) and patelete-derived growth facters-B (PDGF-B) in the process of hepatic fibrosis. And then provide a reliable theoretical basis and practical applications for the prevention and treatment of liver fibrosis.Methods:Fifty healthy mice with male and female in half were randomly divided into five groups:normal group, oil carbon tetrachloride model group, three treatment group with different Matrine doses as15mg/kg,30mg/kg and60mg/kg; ten for each group with male and female in half. According to the way of hepatic fibrosis model which induced by carbon tetrachloride in the science of the method of pharmacological experiments, build up the model of hepatic fibrosis mouse. Mice were sacrificed and the changes of cellular morphology and collagen in liver tissue of each group were estimated by hematoxylin and eosin(HE) and Masson staining.The expression of a-smooth muscle action (a-SMA), TGF-β1and PDGF-B in liver tissues of each group were detected by immunohistochemistry. The expression of TGF-/β1and PDGF-B mRNA were detected by real-time fluorescence quantitative PCR.Results:Oil carbon tetrachloride induced liver fibrosis for8weeks, degeneration and necrosis of liver cells was evident, inflammatory cell infiltration was increased, fibrous tissues proliferous proliferated obviously, and all of these were observed by HE staining. So, liver fibrosis model was induced successfully.The outcomes of HE and Masson staining showed that Matrine groups could improve the structure of liver lobe evidently after acting on the mouse hepatic fibrosis model after four weeks. Degeneration and necrosis of liver cells and inflammatory cell infiltration decreased obviously, and the deposit of collagen fiber reduced too. Furthermore, the fibrous septums were narrowed obviously.Immunohistochemical analysis outcomes showed that compared with model group, Matrine with different doses decreased apparently the expression of α-SMA、 PDGF-B and TGF-/β1in the tissue of liver after acting on the mouse hepatic fibrosis model four weeks, and significant differences was observed (p<0.01). Moreover the expression decreased linearly with the increae of Matrine’s dosage, and60mg/kg doses of Matrine group showed the most strong-est effects.The outcome of real-time fluorescence quantitative PCR showed that, Matrine with different doses decreased obviously the expression of TGF-β1and PDGF-B mRNA after acting on the mouse hepatic fibrosis model four weeks compared with model group. Significant differences was observed(P<0.01), and60mg/kg Matrine group showed the most significant effects.Conclusion:The Matrine can improve structure of liver tissue of mouse with hepatic fibrosis, and inhibit the development of the fibrosis, so as to with therapeutic effect on hepatic fibrosis. The mechanism of Matrine to anti-fibrosis may be as follows:firstly, inhibiting expression of α-SMA in hepatic tissue, thus inhibiting hepatic stellate cell activation. Secondly, inhibiting the expression of TGF-β1and PDGF-B in the tissue of liver.
Keywords/Search Tags:Matrine, Hepatic fibrosis, HSC, α-SMA, TGF-β1, PDGF-B
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