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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[1]ZHOU T, LIU CH, CHEN Y, et al.Guiding role of qi-blood theory in treatment of liver fibrosis due to chronic liver diseases[J].Acta Univ Tradit Med Sin Pharmacol Shanghai, 2007, 21 (2) :34-36. (in Chinese) 周滔, 刘成海, 陈园, 等.气血理论在慢性肝病肝纤维化治疗中的指导作用[J].上海中医药大学学报, 2007, 21 (2) :34-36. [2]TAO YY, CHEN Y, CHEN GF, et al.Anti-hepatic fibrosis effect of“Danggui Buxue Decoction”with different proportions of radix astraga and angelica sinensis in rats[J].Acta Univ Tradit Med Sin Pharmacol Shanghai, 2008, 22 (1) :40-44. (in Chinese) 陶艳艳, 陈园, 陈高峰, 等.当归补血汤不同配比组方的抗肝纤维化作用[J].上海中医药大学学报, 2008, 22 (1) :40-44. [3]LIU CH, LI FH, CHEN WH, et al.Effects of diammonium glycyrrhizinate on the lipid peroxidation and interstitial collagenase activity in fibrotic liver in rat[J].Chin J Pathophysiol, 2005, 21 (11) :2233-2237. (in Chinese) 刘成海, 李风华, 陈文慧, 等.甘草酸二铵对肝纤维化大鼠肝脏脂质过氧化与间质性胶原酶活性的影响[J].中国病理生理杂志, 2005, 21 (11) :2233-2237. [4]JAMALL IS, FINELLI VN, QUE HEE SS.A simple method to determine nanogrnm levels of 4-hydroxyproline in biological tissues[J].Anal Biochem, 1981, 112 (1) :70-75. (in Chinese) [5]FRIEDMAN SL.Evolving challenges in hepatic fibrosis[J].Nat Rev Gastroenterol Hepatol, 2010, 7 (8) :425-436. [6]LIU P, MU YP, LIU CH.Clinical and basic progress of traditional Chinese medicine in chronic liver disease[J].J Clin Hepatol, 2011, 27 (5) :451-457. (in Chinese) 刘平, 慕永平, 刘成海.中医药治疗慢性肝病的临床与基础研究进展[J].临床肝胆病杂志, 2011, 27 (5) :451-457. [7]CHEN Y, TAO YY, LI FH, et al.Effects of Danggul Buxue decoction on liver fibrosis and hepatic lipid peroxidation in rat[J].Chin J Integr Tradit and West Med, 2008, 28 (1) :39-43. (in Chinese) 陈园, 陶艳艳, 刘成海, 等.当归补血汤对大鼠肝纤维化与肝脏脂质过氧化的影响[J].中国中西医结合杂志, 2008, 28 (1) :39-43. [8]BI HZ, ZHANG JT, HUANG GJ, et al.Effects of HGKL on serum IL-1 and IL-6 in HF model rats induced by carbon tetrachloride compounded with other factors[J].Lishizhen Med And Mater Med Res, 2008, 19 (8) :1953-1954. (in Chinese) 毕红征, 章金涛, 黄国钧, 等.HG颗粒对CCl4复合因素致肝纤维化大鼠血清IL-1和IL-6含量的影响[J].时珍国医国药, 2008, 19 (8) :1953-1954. [9]FANG HL, LAI JJ, LIN WL, et al.A fermented substance from Aspergillus phoenicis reduces liver fibrosis induced by carbon tetrachloride in rats[J].Biosci Biotechnol Biochem, 2007, 71 (5) :1154-1161. [10]CHEN LJ, CAI J, ZHAO JJ, et al.Observation of the effect of melatonin on subarachnoid hemorrhage-induced cerebral vasospasm in rats using synchrotron radiation angiography[J].Chin J Cerebrovase Dis, 2012, 9 (5) :259-264. (in Chinese) 陈路佳, 蔡军, 赵京晶, 等.应用同步辐射血管造影观察褪黑素对大鼠蛛网膜下腔出血致血管痉挛的影响[J].中国脑血管病杂志, 2012, 9 (5) :259-264. [11]BOLL H, NITTKA S, DOYON F, et al.Micro-CT based experimental liver imaging using a nanoparticulate contrast agent:a longitudinal study in mice[J].PLoS One, 2011, 6 (9) :1-6. [12]SHAO Y, SONG GP.Clinicopathological analysis of the development of hepatic sinusoidal capillarization in chronic hepatitis patients[J].J Clin Hepatol, 2011, 27 (2) :154-156. (in Chinese) 邵莹, 宋光平.慢性肝炎肝窦毛细血管化的临床病理研究[J].临床肝胆病杂志, 2011, 27 (2) :154-156. [13]ZHANG Q, LIU P, ZHANG HW, et al.Study on the patterns of TCM syndrome differentiation of 900 patients with posthepatitic cirrhosis[J].Chin J Integr Tradit and West Med, 2006, 26 (8) :694-697.张琴, 刘平, 章浩伟, 等.900例肝炎后肝硬化中医证候判别模式的研究[J].中国中西医结合杂志, 2006, 26 (8) :694-697. (in Chinese) [14] Liver Disease Committee, Chinese Association of Integrative Medicine.Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practic[J].Chin J Hepatol, 2006, 14 (11) :866-870. (in Chinese) 中国中西医结合学会肝病专业委员会.肝纤维化中西医结合诊疗指南[J].中华肝脏病杂志, 2006, 14 (11) :866-870. [15]LIU CH, LIU P, HU YY, et al.Progress of clinical and basic research on liver fibrosis with traditional Chinese medicine[J].World Sci Technol-Mod Tradit Chin Med Mater Med, 2007, 9 (2) :112-119. (in Chinese) 刘成海, 刘平, 胡义扬, 等.中医药抗肝纤维化临床与基础研究进展[J].世界科学技术-中医药现代化, 2007, 9 (2) :112-119.
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