Effect of shikonin on expression of TGF-β1 in liver fibrosis induced by CCl4 in rats
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摘要: 目的 观察紫草素对肝纤维化大鼠肝组织病理学改变及转化生长因子-β1（TGF-β1）含量的影响，探讨其对四氯化碳诱导的肝纤维化大鼠抗肝纤维化作用及可能的机制。 方法 将40只SD大鼠随机分为空白组、模型组、阳性对照组、紫草素组。除空白组外，各组大鼠腹腔注射40%四氯化碳橄榄油溶液建立肝纤维化模型。造模同时，空白组与模型组予蒸馏水灌胃，阳性对照组予复方鳖甲软肝片水溶液灌胃，紫草素组予腹腔注射紫草素溶液，共干预10周。观察肝组织病理学变化；采用ELISA法测定层粘连蛋白、Ⅲ型前胶原含量，采用全自动生化仪分析ALT、AST含量，免疫组织化学法检测纤维化肝组织中TGF-β1的表达。 结果 与空白组比较，模型组可见明显肝纤维化病理改变，AST、ALT水平升高（P<0.05），层粘连蛋白、Ⅲ型前胶原含量增高（P<0.05）；与模型组比较，紫草素组肝纤维化程度较轻，血清ALT、ALT水平较低（P<0.05），层粘连蛋白、Ⅲ型前胶原含量下降（P<0.05），肝组织TGF-β1含量下降（P<0.05）；与阳性对照组比较，紫草素组肝组织TGF-β1含量下降（P<0.05）。 结论 紫草提取物紫草素可通过下调四氯化碳诱导的肝纤维化大鼠肝组织中TGF-β1的表达，从而抑制大鼠肝纤维化。Abstract: Objective To observe the influence of shikonin on pathological changes of liver tissue, expression of TGF-β1 in liver fibrosis in rats and to explore the possible mechanism of shikonin on rats' liver fibrosis. Methods 40 SD rats were randomly divided into four groups:normal group,model group,positive controlled group and shikonin group. Except normal group, the liver fibrosis models were introduced by subcutaneously injecting CCl4. Meanwhile, The normal group and the model group were intragastrically given the distilled water. The positive controlled group was intragastrically given Compound Biejiaruangan Troche solution. The treatments lasted for ten weeks. After treatments, pathological changes were observed. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST)of serum were determined by automatic biochemical analyzer. The serum contents of laminin, procollagen type Ⅲ were assayed by ELISA. Transforming growth factor beta 1 (TGF-β1) index level was determined by immunohistochemistry. Results Compared with the normal group, liver fibrosis was detected in the model group. The serum levels of ALT,AST and the serum contents of laminin and procollagen type Ⅲ in the model group were significantly increased (P<0.05). Compared with the model group, the degree of liver fibrosis was less severe in shikonin group. The serum levels of ALT, AST, laminin, procollagen type Ⅲ and the expression of TGF-β1 in liver tissue were all decreased(P<0.05)in shikonin group. Compared with the positive controlled group, the expression of TGF-β1 in liver tissue was reduced in the shikonin group(P<0.05). Conclusion In SD rats, shikonin could inhibit the rats liver fibrosis induced with CCl4 by accommodating TGF-β1 expression in liver tissue.
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Key words:
- shikonin /
- liver fibrosis /
- TGF-β1
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[1] 国家药典委员会.中华人民共和国药典(一部):2015年版[S].北京:中国医药科技出版社,2015:320. [2] 马琴国,李天庆.紫草化学成分及药理作用研究进展[J].甘肃中医学院学报,2013,30(2):78-80. [3] WU H,XIE J,PAN Q,et al. Anticancer agent shikonin is an incompetent inducer of cancer drug resistance[J]. PLoS One,2013,8(1):e52706. [4] 徐佳,伍春莲. 紫草素药理作用研究进展[J].药物生物技术,2015,22(1):87-90. [5] 谢宏晟,蔡丽敏,颜鸣鹤. 恩替卡韦联合扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化的效果观察[J]. 浙江医学,2016,38(8):555-557. [6] 陈红艳,杨光辉.恩替卡韦联合扶正化瘀胶囊对慢性乙型肝炎肝纤维化治疗效果观察[J]. 徐州医学院学报,2015,35(5):335-337. [7] 杨丽敏,李群,窦雯雯,等.卡托普利联合复方鳖甲软肝片用于肝纤维化的临床效果[J].山东医药, 2016, 56(24):53-54. [8] 张宁,方衡,王雪,等.逍遥散对实验性肝纤维化大鼠模型干预作用的代谢组学研究[J].药物分析杂志,2014,4(4):588-594. [9] 彭蕴茹,丁永芳,罗宇慧,等.藏药郎庆阿塔治疗肝纤维化的实验研究.中国实验方剂学杂志,2012,11(18):189-194. [10] 白辰,车念聪,刘文兰,等.一贯煎对大鼠肝纤维化拮抗作用的影响.中华中医药杂志,2015,30(3):815-817. [11] 罗瑞红,杨绍基.转化生长因子-β1与肝纤维化[J].国外医学(内科学分册),2000,27(8):348-350. [12] 陈洪,陆亚琴,刘顺英,等.地龙2号对大鼠肝纤维化α-SMA、TGF-β1、MMP13及TIMP-1蛋白表达的影响[J].胃肠病学和肝病学杂志,2005,14(2):156-159. [13] 高萍,程留芳,杨云生.TGFβ与肝纤维化关系研究进展[J].现代中西医结合杂志2006,15(9):1272-1274. [14] 詹志来,胡峻,刘谈,等.紫草化学成分与药理活性研究进展[J].中国中药杂志,2015,40(21):4127-4135. [15] 龙大碧,李晓兰,李远.肝纤维化无创诊断与监测技术研究进展[J].中华实用诊断与治疗杂志,2011,25(11):1045-1046. [16] 王继贵.肝纤维化生物标志物研究的进展[J].实验与检验医学,2011,29(2):138-141. -
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