摘要
目的:探讨下瘀血汤对四氯化碳(carbon tetrachloride,CCl4)诱导的大鼠肝硬化形成过程中肝脏血管新生的影响。方法:采用50%CCl4-橄榄油溶液1mL/kg剂量腹腔注射,每周2次,共9周,制备大鼠肝硬化模型。造模3周和6周后,随机抽取正常及模型大鼠各6只,处死作动态观察,其余模型大鼠随机分为模型对照组(15只)和下瘀血汤组(11只),同龄正常大鼠6只设为正常对照。自第7周开始灌胃给予下瘀血汤干预治疗3周,于第9周末取材,苏木精和伊红染色及天狼星红染色观察肝组织病理学变化,免疫荧光法和蛋白质印迹法检测肝组织中血小板内皮细胞黏附分子1(platelet endothelial cell adhesion molecule-1,CD31)、第Ⅷ因子相关抗原(von Willebrandfactor,v WF)的表达,蛋白质印迹法检测肝组织中血管内皮生长因子(vascular endothelialgrowth factor,VEGF)、血管内皮生长因子受体2(VEGF receptor-2,VEGFR2)、补体衰变加速因子(complement decay-accelerating factor,DAF)和α平滑肌肌动蛋白(α-smooth actin,α-SMA)的表达,明胶酶谱法检测肝组织中基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)和MMP-9的活性。结果:与正常组比较,模型大鼠肝组织受损,脂肪变性显著,胶原纤维沉积严重,随造模时间的推移,肝组织CD31、v WF、VEGF、VEGFR2、DAF和α-SMA蛋白表达逐渐升高,MMP-2、MMP-9活性显著增强(P<0.01)。与9周模型组比较,下瘀血汤显著改善肝组织损伤、脂肪变性及胶原纤维的沉积,降低肝组织CD31、v WF、VEGF、VEGFR2、DAF和α-SMA蛋白的表达及MMP-2、MMP-9的活性(P<0.01)。结论:下瘀血汤可有效地抑制CCl4诱导的大鼠肝硬化形成过程中的血管新生,其作用机制主要在于抑制肝星状细胞的活化,下调MMP-2、MMP-9的活性以及消解新生血管的完整性。
Objective：To evaluate the effects of Xiayuxue Decoction,a compound traditional Chinese medicine,on liver angiogenesis in rats with carbon tetrachloride（CCl4）-induced liver fibrosis.Methods：Liver cirrhosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at the dose of 1 mL/kg body weight,twice per week for 9 consecutive weeks.After 3-and 6-week injection,6 rats in the normal group and 6 rats in the model group were randomly sacrificed for dynamic observation.The survival rats of model group were randomly divided into model group（n=15）and Xiayuxue Decoction group（n=11）.Six normal rats were used as a normal control.Xiayuxue Decoction was administered orally starting from the 7th week for 3 weeks.At the end of the ninth week,animals were sacrificed and liver tissues were harvested to measure histological changes,activities of matrix metalloproteinase-2（MMP-2）and MMP-9 and protein expressions of platelet endothelial cell adhesion molecule-1（CD31）,von Willebrand factor（vWF）,vascular endothelial growth factor（VEGF）,vascular endothelial growth factor receptor-2（VEGFR2）,complement decay-accelerating factor（DAF）and α-smooth muscle actin（α-SMA）in the liver tissues.Results：Compared with the normal group,liver injury,fatty degeneration and collagen deposition were evidently observed in the model group and protein expressions of CD31,vWF,VEGF,VEGFR2,DAF and α-SMA were gradually increased.In addition,the activities of MMP-2 and MMP-9 in liver tissues were enhanced in the model group（P〈0.01）.Compared with 9-week model group,liver injury,fatty degeneration and collagen deposition were markedly inhibited by Xiayuxue Decoction;protein expressions of CD31,vWF,VEGF,VEGFR2,α-SMA and DAF and activities of MMP-2 and MMP-9 in the liver tissues were decreased in the Xiayuxue Decoction group（P〈0.01）.Conclusion：The angiogenesis is evident and aggravating gradually during the progression of liver cirrhosis induced by CCl4.Xiayuxue Decoction inhibits the a
出处
《中西医结合学报》
CAS
2011年第8期878-887,共10页
Journal of Chinese Integrative Medicine
基金
国家重点基础研究发展计划(973计划)资助项目(No.2006CB504801)
国家自然科学基金重大研究计划重点资助项目(No.90409020)
上海市教育委员会上海高校创新团队(第一期)建设项目
上海市教育委员会E-研究院建设计划资助项目(No.E03008)
关键词
四氯化碳
肝硬化
血管新生
中草药
大鼠
carbon tetrachloride
liver cirrhosis
angiogenesis
drugs, Chinese herbal~ rats
