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Therapeutic effect of Danggui Buxue decoction and its separated recipes on liver fibrosis and angiogenesis and its mechanism
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摘要:
目的观察当归补血汤及其拆方影响肝脏血管新生的抗肝纤维化的药效特点。方法 48只Wistar大鼠随机分为正常组、模型组、当归补血汤组、黄芪组、当归组及索拉非尼对照组。以四氯化碳(CCl4)与高脂低蛋白饮食复合因素诱导肝纤维化模型。通过病理对肝组织形态学进行观察,试剂盒测定血清肝功能、肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、一氧化氮合酶(NOS);盐酸水解法测定肝组织羟脯氨酸(Hyp);电镜观察肝窦内皮窗孔结构;同步辐射X线二维成像观察微血管。组间比较使用单因素方差分析,方差齐时用LSD进行两两比较,方差不齐时用Tamhane’s T2。结果当归补血汤及其拆方组白蛋白(Alb)显著提高(P<0.05)、AST显著降低(P<0.05);当归补血汤及黄芪组ALT显著降低(P<0.05);各用药组肝组织Hyp含量显著降低。各用药组血管纹理有不同程度的减少;窗孔数量增加。当归补血汤及其拆方组SOD活性显著升高(P<0.05),全方及拆方组NOS显著降低(P<0.05),黄芪组MDA显著降低(P<0.05),全方组及黄芪组NO显著降低(...
Abstract:Objective To observe the pharmacodynamic characteristics of Danggui Buxue decoction (containing Angelica sinensis) and its separated recipes in treating liver fibrosis and angiogenesis.Methods Forty- eight Wistar rats were randomly divided into 6 groups:normal group, model group, Danggui Buxue decoction group, Astragalus membranaceus group, Angelica sinensis group, and sorafenib control group.In all groups except normal group, a rat model of liver fibrosis was established using carbon tetrachloride combined with high- fat and low-protein diet.Liver tissue inflammation was observed by HE staining, while collagen deposition by Sirius red staining.Serum levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , and albumin (Alb) and the malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, nitric oxide (NO) content, and nitricoxide synthase (NOS) activity in liver tissue were determined by a test kit.The hydroxyproline (Hyp) content in liver tissue was determined by hydrochloric acid hydrolysis.Sinusoidal endothelial fenestrae were observed by scanning electron microscope, and liver capillaries by synchrotron radiation X- ray two- dimensional imaging.Comparisons between groups were made by one- way analysis of variance;the least significant difference test was used when variances were equal, and the Tamhane's T2 test was used when variances were unequal.Results The Danggui Buxue decoction group, Astragalus membranaceus group, and Angelica sinensis group had significantly increased serum Alb levels (P < 0.05) and significantly decreased serum AST levels (P < 0.05) ;the Danggui Buxue decoction group and Astragalus membranaceus group had significantly decreased serum ALT levels (P < 0.05) .All treatment groups had significantly decreased liver hydroxyproline content (P < 0.05) .In the liver tissues of all treatment groups, the vascular texture was reduced, and the number of sinusoidal endothelial fenestrae was increased.The Danggui Buxue decoction group, Astragalus membranaceus group, and Angelica sinensis group had significantly increased SOD activity (P < 0.05) and significantly decreased NOS activity (P < 0.05) ;the Astragalus membranaceus group had significantly decreased liver MDA content (P < 0.05) ;the Danggui Buxue decoction group and Astragalus membranaceus group had significantly decreased liver NO content (P < 0.05) .Conclusion Danggui Buxue decoction and its separated recipes have good efficacy in treating liver fibrosis and angiogenesis.The mechanism may involve protecting liver sinusoidal endothelial cells and reducing lipid peroxidation.Astragalus membranaceus is superior to Angelica sinensis in reducing inflammation, lipid peroxidation, and NO release.
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Key words:
- liver cirrhosis /
- angiogenesis /
- DANGGUI BUXUE DECOCTION /
- astragalus membranaceus /
- angelica sinensis
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