柴虎疏肝煎剂对肝纤维化大鼠细胞因子的影响
摘要
目的观察柴虎疏肝煎剂对肝纤维化大鼠肿瘤坏死因子-α(tumor necrosis fac-tor-α,TNF-α)和干扰素-γ(interferon-γ,INF-γ)的影响,并且观察该药对大鼠肝纤维化治疗作用及意义。方法80只Wistar大鼠随机分为正常组、模型组组、中药金三莪预防组及治疗组、柴虎疏肝煎剂预防组、柴虎疏肝煎剂低、中、高剂量治疗组,共8组,每组10只。除正常组以外,其余各组以40%四氯化碳(Carbon tetrachloride,CCL4)石蜡油造模,中药金三莪预防组和柴虎疏肝煎剂预防组在造模同时分别给予中药金三莪和柴虎疏肝煎剂。造模4周后灌胃治疗,各治疗组分别给予相应剂量的中药治疗8周。病理切片观察各组大鼠肝纤维化程度,免疫组织化学技术检测两种细胞因子在组织标本中的表达,利用酶联免疫吸附法(ELISA)检测各组血清中TNF-α和INF—γ的浓度。结果病理学结果:与正常组相比,模型组及柴虎疏肝煎剂低剂量组肝纤维化明显,差异有统计学意义(P<0.01)。与模型组相比,柴虎疏肝煎剂中、高剂量组肝纤维化程度明显减轻(P<0.05)。免疫组化结果:与正常组相比,模型组、柴虎疏肝煎剂低剂量组INF-γ表达明显增强(P<0.01)。与模型组相比,中药金三莪治疗及预防组,柴虎疏肝煎剂预防、中、高剂量治疗组INF-γ表达明显减弱(均为P<0.01)。与正常组相比,模型组和柴虎疏肝煎剂低剂量治疗组TNF-α表达明显增强(P<0.05)。与模型组相比,中药金三莪预防及治疗组、柴虎疏肝煎剂预防及中、高剂量组TNF-α表达明显减弱,(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01)。血清学结果:与正常组相比,模型组血清中IFN-γ的浓度明显升高(P<0.01),与模型组相比,柴虎疏肝煎剂中、高剂量治疗组血清中IFN-γ浓度明显降低(P<0.01)。与正常组相比,模型组血清中TNF-α浓度明升高(P<0.01)。与模型组相比,中药金三莪预防组及治疗组、柴虎疏肝煎剂预防组、柴虎疏肝煎剂低、中、高剂量治疗组血清中TNF-α浓度明显降低(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01、P<0.01)。结论柴虎疏肝煎剂可能主要是通过降低肝纤维化大鼠血清中细胞因子IFN-γ和TNF-α的浓度,并且降低TNF-α和IFN-γ在肝纤维化大鼠肝组织中的表达,进一步抑制肝脏的炎症反应,减轻肝脏损伤而起到治疗肝纤维化的作用,为临床中医用药提供实验依据。
Objective To observe the effect of ChaiHu ShuGan decotion on cytokines tumor necrosis factor-α(TNF-α)、interferon-γand observe the effect of this Traditional Chinese Medicine on rats with hepatic fibrosis.Method The eighty rats were divided into eight groups randomly, every group included ten rats. They were control group、model group、Traditional Chinese Medicine JinSanE preventive group、ChaiHu ShuGan decotion preventive group、Traditional Chinese Medicine JinSanE therapeutic group、ChaiHu ShuGan decotion low dosage、middle dosage、high dosage therapeutic group. Except control group, the other groups were given 40% carbon tetrachloride liquid paraf-fin to make model of hepatic fibrosis . Traditional Chinese Medicine JinSanE preventive group and ChaiHu ShuGan decotion preventive group were administrated Traditional Chinese Medicine JinSanE and traditional Chinese drugs ChaiHu ShuGan decotion re-spectively when the model began to make. Four weeks later , the therapeutic groups were administrated the traditional Chinese drugs JinSanE and ChaiHu ShuGan decotion eight weeks .The concentration of TNF-αand INF-γin the serum of rats in every group were de-tected by enzyme linked immunosorbent assay(ELISA);the degree of hepatic fibrosis of rats was detected by pathological section ;the degree of the two cytokines expressed in liver were detected by immunohistochemistry .Result The result of pathology, com-pared with control group , the degree of hepatic fibrosis of model group and ChaiHu ShuGan low dosage therapeutic groups obviously and had difference significance(P<0.01).Compared with model group ,the degree of hepatic fibrosis of ChaiHu ShuGan de-cotion middle and high dosage group were improved obviously and had difference sig-nificance(P<0.05). The result of immunohistochemistry , compared with control group, the expression of IFN-γin liver of rats of model group and ChaiHu ShuGan decotion low dosage therapeutic groups was enhanced obviously and had difference significance (P<0.01). Compared with model group, the expression of IFN-γin liver of rats of Traditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine JinSanE therapeutic groups、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan decotion m i d d l e a n d h i g h d o s a g e t h e r a p e u t i c g r o u p s w a s w e a kened obviously and had difference significance(P<0.01). Compared with control group, the expression of TNF-αin liver of rats of model group and ChaiHu ShuGan decotion low dosage therapeutic groups was enhanced obviously and had difference significance (P<0.05). Compared with model group, the expression of TNF-αin liver of rats of Tra-ditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine therapeutic group、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan de-cotion middle and high dosage therapeutic groups was weakened obviously and had dif-ference significance(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01).The reslutof serology, compared with control group, the concentration of IFN-γin serum of model group was increased obviously and had difference significance(P<0.01). Compared with model group ,the concentration of IFN-γin serum of ChaiHu ShuGan decotion middle and high dosage therapeutic groups was decreased obviously and had difference sig-nificance (P<0.01). Compared with control group, the concentration of TNF-αin se-rum of model group was increased obviously and had difference significance(P<0.01).Compared with model group ,the concentration of TNF-αin serum of Traditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine JinSanE therapeutic group、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan decotion low dosage、middle dosage、high dosage therapeutic group was decreased obviously and had difference significance(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01、P<0.01).
Conclusion ChaiHu ShuGan decotion play a role in improvement of hepatic fibrosis of rats possibly mainly by decreasing the concentration of TNF-αand INF-γin serum and decreasing the expression of TNF-αand IFN-γin liver of rats with hepatic fibro-sis ;and then inhabiting inflammation and decreasing injury of liver. This research hoped to give experimental basis on clinical treatment.
Objective To observe the effect of ChaiHu ShuGan decotion on cytokines tumor necrosis factor-α(TNF-α)、interferon-γand observe the effect of this Traditional Chinese Medicine on rats with hepatic fibrosis.Method The eighty rats were divided into eight groups randomly, every group included ten rats. They were control group、model group、Traditional Chinese Medicine JinSanE preventive group、ChaiHu ShuGan decotion preventive group、Traditional Chinese Medicine JinSanE therapeutic group、ChaiHu ShuGan decotion low dosage、middle dosage、high dosage therapeutic group. Except control group, the other groups were given 40% carbon tetrachloride liquid paraf-fin to make model of hepatic fibrosis . Traditional Chinese Medicine JinSanE preventive group and ChaiHu ShuGan decotion preventive group were administrated Traditional Chinese Medicine JinSanE and traditional Chinese drugs ChaiHu ShuGan decotion re-spectively when the model began to make. Four weeks later , the therapeutic groups were administrated the traditional Chinese drugs JinSanE and ChaiHu ShuGan decotion eight weeks .The concentration of TNF-αand INF-γin the serum of rats in every group were de-tected by enzyme linked immunosorbent assay(ELISA);the degree of hepatic fibrosis of rats was detected by pathological section ;the degree of the two cytokines expressed in liver were detected by immunohistochemistry .Result The result of pathology, com-pared with control group , the degree of hepatic fibrosis of model group and ChaiHu ShuGan low dosage therapeutic groups obviously and had difference significance(P<0.01).Compared with model group ,the degree of hepatic fibrosis of ChaiHu ShuGan de-cotion middle and high dosage group were improved obviously and had difference sig-nificance(P<0.05). The result of immunohistochemistry , compared with control group, the expression of IFN-γin liver of rats of model group and ChaiHu ShuGan decotion low dosage therapeutic groups was enhanced obviously and had difference significance (P<0.01). Compared with model group, the expression of IFN-γin liver of rats of Traditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine JinSanE therapeutic groups、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan decotion m i d d l e a n d h i g h d o s a g e t h e r a p e u t i c g r o u p s w a s w e a kened obviously and had difference significance(P<0.01). Compared with control group, the expression of TNF-αin liver of rats of model group and ChaiHu ShuGan decotion low dosage therapeutic groups was enhanced obviously and had difference significance (P<0.05). Compared with model group, the expression of TNF-αin liver of rats of Tra-ditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine therapeutic group、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan de-cotion middle and high dosage therapeutic groups was weakened obviously and had dif-ference significance(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01).The reslutof serology, compared with control group, the concentration of IFN-γin serum of model group was increased obviously and had difference significance(P<0.01). Compared with model group ,the concentration of IFN-γin serum of ChaiHu ShuGan decotion middle and high dosage therapeutic groups was decreased obviously and had difference sig-nificance (P<0.01). Compared with control group, the concentration of TNF-αin se-rum of model group was increased obviously and had difference significance(P<0.01).Compared with model group ,the concentration of TNF-αin serum of Traditional Chinese Medicine JinSanE preventive group、Traditional Chinese Medicine JinSanE therapeutic group、ChaiHu ShuGan decotion preventive group、ChaiHu ShuGan decotion low dosage、middle dosage、high dosage therapeutic group was decreased obviously and had difference significance(P<0.05、P<0.01、P<0.05、P<0.05、P<0.01、P<0.01).
Conclusion ChaiHu ShuGan decotion play a role in improvement of hepatic fibrosis of rats possibly mainly by decreasing the concentration of TNF-αand INF-γin serum and decreasing the expression of TNF-αand IFN-γin liver of rats with hepatic fibro-sis ;and then inhabiting inflammation and decreasing injury of liver. This research hoped to give experimental basis on clinical treatment.
引文
[1]潘陈为,陈永平.抗肝纤维化重组TGF-β疫苗的研究进展[J].国外医学流行病学传染病学分册,2005,32(2):96-98
[2] Wook-Hwan Kim,Kunio Matsumoto ,Kazuhiko Bessho.et al .Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to reso-lution from liver cirrhosis[J].American Journal of Pathology,2005,166, 1017-1028
[3]武哲丽,陈群,徐志伟等.论中药复方抗肝纤维化的证治研究[J].中医药学刊,2006, 24(1):489-490
[4] Jie-Ting Tang, Jing-Yuan Fang, Wei-Qi Gu, et al .T cell immune response is corre-lated with fibrosis and inflammatory activity in hepatitis B cirrhotics[J] World journal of Gastroenterol,2006,12(19):3015-3019
[5] Viao Chen,Guang-jing Wang,Yong Diao,et ladino-associated virus mediated inter-feron-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo[J]. World journal of Gastroenterology,2006,11(26):4045-4051
[6] A.M.Gressner,R.Weisirchen. Modern pathogenic concepts of liver fibrosis suggest satellite cells and TGF-βas major players and therapeutic targets[J].Journal of cellular and molecular medicine,2006,10(1):76-99
[7] Li-Juan Xiong,Duan-De Luo,Lin-Lan Zen, et al .Effects of pentoxifylline on the he-patic content of TGF-β1 and collagen in Schistosomiasis japonica mice with liver fi-brosis[J].World journal of Gastroenterol, 2003,9(1):152-154
[8]宋仕玲,龚作炯,张全荣等.金三莪对实验性大鼠TGF-β1、Smad3、Smad7及CTGF表达的影响[J].天津中医药,2004,21(1):62-64
[9] Li-Juan Zhang, Jie-Ping Yu, Dan Li, et al. Effects of cytokines on carbon tetrachlo-ride-induced hepatic fibro genesis in rats[J]. World journal of Gastroenterol,2004 , 10(1):77-81
[10] Van horssen R,Ten Hangen TL,Eggermant AM.TNF-alpha in cancer treatment mo-lecular insight ,antitumor effect and clinical until y [J].The journal of oncolo-gist,2006,11(4):397-408
[11] Schwabe RF,Brenner DA. Mechanisms of liver injuryⅠ,TNF-alpha-induced liver in-jury: role of IKK,JNK and ROS pathways[J].American journal of Castrointest liver physiology,2006,290(4):583-589
[12] Lin SY,Chen WY,Chin YT,et,al. Different tumor necrosis factor-alpha-associatedleptin expression in rats with dimethylnitrosamine and bile duct ligation-induced liver cirrhosis[J].The journal of metabolism,2005,54(4):445-452
[13] Mallat.A,Preaux AM,Blaze Jewskis,et al.Interferon alfa and gamma inhabit prolifera-tion and collagen synthesis of human ito cell in culture[J].Hepatology. 1995, 21(4):1003-1010
[14] Levent Kabasakal, Meral Yuksel, Nursal Gedik,et.al. Hepatic fibrosis in bil-iary-obstructed rats is prevented by Ginkgo biloba treatment [J].World journal of Gastroenterol,2005 ,(35):5444-5449
[15]孙永年,黄视青徐斌等.慢性乙型肝炎患者血清细胞因子与肝纤维化的关系[J].中国医师杂志,2004,6(5):41-43
[16] Jeng Jen-Eing,Tsai Jung-Fa,Chuang Lee-Yea,et,al.tumor necrosis factor—α308.2 polymorphism is associated with advanced hepatic fibrosis and high risk for hepato-cellular carcinoma[J].Neoplasia,2007,9(11):987-992
[17]牛春红,韩得五,刘近春等. TNF-α和IL-10在肝硬化发生中的动态变化的研究[J].中国病理生理杂志,2006;22(12):2467-2473
[18] Amélia Ribeiro de Jesus, Andréa Magalh?es,1Delfin Gonzalez Miranda,et al. Associa-tion of Type 2 Cytokines with Hepatic Fibrosis in Human Schistosoma mansoni In-fection[J]. Infection and immunity,2004 ,72(6):3391-3397
[19]周建华.肝纤维华、肝硬化不同阶段细胞因子的变化[J].中国基层医药,2007, 14(6):954-955
[20] Nammous AH,Pietruczk M,Zukack D,et,al. Structure and biologic function of IFN-gamma[J].Rrzeglad lekarski,2005,62(9):890-893
[21] Yong HA,Bream JH.IFN-gamma :recent advances in understanding regulation of ex-pression, biological function,and clinical application[J].Current top microbiology immunology,2007,316:97-117
[22] Strehl B,Seifert U,Kruger E,et,al.Interferon-gamma,the functional plasticity of the uniquitin-proteasome system, and MHC classⅠantigen processing[J]. Immunology review, 2005,207:19-30
[23] Christophe Cheullard,Carole Eboumbou Moukoko,Nast-Eldin M.A.et al.IFN-γpoly-morphisms(IFN-γ+2109 and IFN-γ+3810) are associated with sever hepatic fibrosis in human hepatic schistosomiasis(schistosoma mansoni) [J].Journal of immunol-ogy,2006,171:5596-5601
[24] Kumar M,Sarin sk.Is cirrhosis of the liver reversible[J].Indian journal of pediat-rics,2007,74(4):393-399
[25] Hammel P,Couvelard A,OTtoole D,Ratouis A,Sauvanet A.Regression of liver fibrosis after billiard drainage in patients with chronic pancreatitis and stenos is of the com-mon bile duct[J].New England journal , 2001,344:418-423
[26] Yue-Hong Huang,Mei-Na Shi,Wei-Da Zheng,et,al.Thereapeutic effect of inter-leukin-10 on CCL4 induced hepatic fibrosis in rats[J]. World journal of Gastroen-terology,2006,12(9):1386-1391
[27] Canbay A, Taimr P, Torok N,et al. Apoptotic body engulfment by a human satellite cell line is profibrogenic[M].Lab Invest,2003,83:655-663
[28]何伟,周伟,沈薇.肝细胞生长因子抗肝纤维化作用及其机制探讨[J].胃肠病学和肝病学杂志,2006,15(6):593-596
[29]尹桂兰.中医药治疗肝纤维化研究近况[J].江苏中医药,2004,25(8):58-60
[30]刘君炎,邓长生,时绍红.银杏叶提取物抗大鼠肝纤维化的实验研究[J].临床消化病杂志,2004,16(1):15-18
[31]杨玲,钱伟,候小华等.莪术提取物对肝纤维化大鼠的血管紧张素Ⅱ及其Ⅰ受体的影响[J].中华肝脏病杂志,2004,14(4):303-305
[32]赵进军,吕志平.白背叶根在肝纤维化动物模型中抗氧化作用的实验研究[J].中药材杂志,2003,25(3):185-187
[33]张万国,胡晋红,蔡溱.桑黄调节细胞因子及其在抗肝纤维化中的意义[J].中国新医药,2003,2(6):19
[34]宋仕玲,龚作炯,张全荣等.中药金三莪方对对实验性肝纤维化大鼠结缔组织生长因子及转化生长因子β1mRNA表达的定位影响[J].解放军医学杂志,2004,(2): 130-133
[35]王胜春,胡咏武,赵辉萍.柴胡与丹参配伍抗大鼠肝纤维化作用的实验研究[J].中国药房,2001,10(10):586-588
[36]陈奇主编.《中药药理实验》[M].贵州人民出版社,1988,158
[37]中华医学会传染病学寄生虫病学分会、肝病学分会联合修订.病毒性肝炎防治方案[J].中华肝脏病杂志,2000,8(6):324-329
[38]杨炼,管小琴,李圆圆.肝硬化和肝癌患者干组织中TGF-β1、TNF-α的表达与HBV感染的关系[J].重庆医科大学学报,2005,30(1):23-26
[39]唐阁,陈文慧.肝纤维化的中医治法研究近况[J].中华中医药杂志,2005,20(6): 361-363
[40] Kiminori Kimura,Kazuki Ando,Hiroo Ohnishi,et,al.Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administrated concanavalin A[J].International immunology,1999,11(9):1491-1500
[41]陈玮,陈维雄,陆允敏等.川芎嗪干预大鼠实验性肝纤维化的研究[J].世界临床药物,2007,28(9):522-525
[42]马周旺,杨俊杰,程卫东等.强肝丸预防四氯化碳诱导的大鼠肝纤维化的实验研究[J].陕西中医,2007,28(11):1561-1563
[43]栾希英,李珂珂,韩兆东.三棱莪术对肝纤维化大鼠IL-1 IL-6 TNF-α的影响.中医中药与免疫,2004,20:834-837
[44] Wang H,Wei W,Wang NP,et,al.melatonin ameliorates Carbon-tetrachloride–induced hepatic fibrogenesis in rats[J].Life Science,2005,77(15):1902-1915
[45] Peng Lv, Shelley Chireyath Paul, Yanjv Xiao,et,al. Effects of Thalidomide on the Ex-pression of Adhesion Molecules in Rat Liver Cirrhosis[J]. Mediators Inflammation. 2006, 2006(4): 932-953
[46]施建平,余小虎,邱夏地.苦参素联合复方丹参对慢性乙型肝炎患者肝纤维化血清学指标、TNF-α和瘦素的影响[J].中国胃肠病学杂志,2007, 12(5):288-290
[47]朱本贵,李昌平,陈霞等.疏肝颗粒对酒精性纤维化的疗效及其机制的实验研究[J].中国中西医结合消化杂志,2006 2,14(1):8-10
[48]孙龙,孙琳琳,杨世忠.肝纤溶颗粒对肝纤维化大鼠血清TNF-α、IL-6水平的影响[J].中国老年学杂质,2006,26(7):1069-1070
[49]王菲张书文.升清降浊丸对免疫性肝损伤模型小鼠细胞因子TNF-α、IL-1、TNF-α、IL-6、IFN-γ的影响[J].世界中西医结合杂志,2007,2(4):210-212
[50]杨小云,观小辉,曾宏等.白细胞介素-18、γ-干扰素与慢性乙型肝炎肝纤维化临床与病理的关系[J].Guangdong Medical Journal,2007 8,28(8):1250-1251
[1]彭彦辉,刘殿武,郝玉斌等.中药方剂对肝纤维化大鼠肝脏ALR基因表达的影响[J].疾病控制杂志,2006,10(4):335-338
[2]张丰,曹苇,王玮等.肝硬化大鼠模型及合并感染时TNF-α和IL-6的基因表达[J].中华肝胆外科杂志,2006,12(4):285-286
[3] Xiao-Zhong Wang,Li-Yuan Zhang,Dan,et,al.Effect of transmitters and interleukin-10 on rat hepatic induced by CCL4[J].Journal of world Gastroenterol, 2003, 9(3):539-543
[4]万昌武,谢汝佳,韩冰等.肝纤维化大鼠肝组织中TGF-β1的表达和细胞外胶原沉积及中药抗肝纤维化治疗的影响[J].贵州医药,2005,29(9):731-734
[5]谢渭芬,林勇.肝纤维化治疗进展[J].实用临床医药杂志,2005,9(7):14-17
[6] Xiang-Wei,MengBao-Rong Chi,Li-Gang,et,al.Expression of interferon-alpha/beta re-ceptor protein in liver of patients with hepatitis C virus-related chronic liver dis-ease[J].The journal of world Gastroenterol,2005,11(25):3962-3965
[7] Henri S,Chevillard C,Mergani A,et al.Cytokine reglantion of periportal fibrosis in humans infected with Schistosomamansoni :IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation disease [J]. Journla of Immunol-ogy ,2002,169:229
[8] Keiding S,Radsherg JH,Becker U,et al .The prognosis of patients with alcoholic liver disease:An international randomized placebo-controlled trial on the effect of sur-vival[J].Journal of Hepatology,1999,20:454-460
[9]华海婴,郭旭光,杨波等.示丹参酮Ⅱ磺酸钠注射液对人肝星状细胞的影响[J].中药药理与临床,2007,23(6):12-14
[10]曾维政肝纤维化治疗策略[J].成都军区医院院报,2003,5(2):23-26
[11]黄古叶,胡振斌,毛德文等.健肝散抗慢性乙型肝炎及其机制研究[J].现代中医药, 2007, 27(6):11-13
[12]胡方平,蒋欣,林勇等.肝纤维化基因治疗新策略[J].中国肝脏病杂志,2007,12(6): 495-497
[13] UEKI KANEKA Y,TSU TSUI H,et al.Hepatocyte growth factor gene therapy of liver cirrhosis in rats[J].淮Nature Mendicine 1999,5(2):226-230
[14] Zhong Z,Froh M,Wheeler MD,et,al.Viral gene delivery of superoxide dismutase at-tenuates experimental cholestasis-induced liver fibrosis in the rats[J]. Gene ther-apy,2002,9:183-191
[15]管军.苦参素治疗乙肝所致肝纤维化临床疗效观察[J].海南医学,2008,19(2):7-8
[16]王怡,薛少礼,薛青等.三七总皂甙对传代肝星型细胞的影响[J].淮南医药,2008, 26(1):1-2
[17]舒建清,王红利,叶国荣等.姜黄素治疗肝纤维化及相关细胞因子的变化研究[J].中药材杂志,2007,30(11):1421-1422
[18]熊振芳,朱清静,杨玲等.莪术提取物对血小板缘性生长因子诱导的HSC细胞内Ca2+和PB-K的影响[J].中西医结合肝病杂志,2007,17,(6):358-360
[19]陈绍兵,陈军华,王玉婷等.甘草酸速对幼龄大鼠实验性肝纤维化的疗效的研究[J].第三军医大学学报,2007,29(23):2261-2263
[20]陈东平,杜慧燕,朱丽萍.大黄对慢性肝炎肝纤维化指标的影响[J].实用中西医结合临床,2007,7(6):87-88
[21]化海婴,李艳瑛,戈士文.川芎嗪抗大鼠免疫损伤性肝纤维化作用及机制研究[J].中药药理与临床,2007,23(5):60-62
[22]刘玉侃,沈薇,张霞.虫草菌丝对实验性肝纤维化的防治作用及其机制研究[J].中国新药与临床杂志,2004,23:139-143
[23]张万国,胡晋红,蔡溱.桑黄调节细胞因子及其在抗肝纤维化中的意义[J].中国新医药,2003,2(6):19
[24]杨错,刑立国,刘玉兰.柴胡对大鼠实验性肝纤维化的预防作用[J].实用药物与临床,2005,8(5):12-14
[25]刘化生,张玲,周景华.柴胡桂枝汤对肝纤维化大鼠转化生长因子β1表达的影响[J].现代中西医结合杂志,2007,16(16):2198-2199
[26]王朝阳,李孝生,尚军洁.川芎嗪与大黄酸联用对大鼠免疫性肝纤维化的治疗作用[J].中国中西医结合消化杂志,2007,15(2):95-98
[27]李蓉,陆伟,赵梦云.黄芪鸡血藤汤对大鼠肝纤维化的预防作用[J].中国中西医结合消化杂志,2007,15(2):99-101
[28]赵红宇,李文斌,灵芝孢子粉抗肝纤维化作用的实验研究[J].中国实用医药2007, 2(5):12-14
[29]晏丹,陈建明,舒赛男等.水蛭桃仁汤对肝纤维化大鼠HSC活化及TGF-β1表达的影响[J].中西医结合肝病杂志,2004,14(1):36
[30]袁强,何岚,陈艺云等.复方鳖甲软肝片对肝纤维化大鼠血管紧张素Ⅱ及其受体mRNA的影响[J].中华中医药杂志,2008,23(2):158-161
[31]张超贤,乔汉臣,杨道坤.三甲益肝冲剂对肝纤维化大鼠结缔组织生长因子表达的影响[J].新乡医学院院报,2008,25(1)9-12
[2] Wook-Hwan Kim,Kunio Matsumoto ,Kazuhiko Bessho.et al .Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to reso-lution from liver cirrhosis[J].American Journal of Pathology,2005,166, 1017-1028
[3]武哲丽,陈群,徐志伟等.论中药复方抗肝纤维化的证治研究[J].中医药学刊,2006, 24(1):489-490
[4] Jie-Ting Tang, Jing-Yuan Fang, Wei-Qi Gu, et al .T cell immune response is corre-lated with fibrosis and inflammatory activity in hepatitis B cirrhotics[J] World journal of Gastroenterol,2006,12(19):3015-3019
[5] Viao Chen,Guang-jing Wang,Yong Diao,et ladino-associated virus mediated inter-feron-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo[J]. World journal of Gastroenterology,2006,11(26):4045-4051
[6] A.M.Gressner,R.Weisirchen. Modern pathogenic concepts of liver fibrosis suggest satellite cells and TGF-βas major players and therapeutic targets[J].Journal of cellular and molecular medicine,2006,10(1):76-99
[7] Li-Juan Xiong,Duan-De Luo,Lin-Lan Zen, et al .Effects of pentoxifylline on the he-patic content of TGF-β1 and collagen in Schistosomiasis japonica mice with liver fi-brosis[J].World journal of Gastroenterol, 2003,9(1):152-154
[8]宋仕玲,龚作炯,张全荣等.金三莪对实验性大鼠TGF-β1、Smad3、Smad7及CTGF表达的影响[J].天津中医药,2004,21(1):62-64
[9] Li-Juan Zhang, Jie-Ping Yu, Dan Li, et al. Effects of cytokines on carbon tetrachlo-ride-induced hepatic fibro genesis in rats[J]. World journal of Gastroenterol,2004 , 10(1):77-81
[10] Van horssen R,Ten Hangen TL,Eggermant AM.TNF-alpha in cancer treatment mo-lecular insight ,antitumor effect and clinical until y [J].The journal of oncolo-gist,2006,11(4):397-408
[11] Schwabe RF,Brenner DA. Mechanisms of liver injuryⅠ,TNF-alpha-induced liver in-jury: role of IKK,JNK and ROS pathways[J].American journal of Castrointest liver physiology,2006,290(4):583-589
[12] Lin SY,Chen WY,Chin YT,et,al. Different tumor necrosis factor-alpha-associatedleptin expression in rats with dimethylnitrosamine and bile duct ligation-induced liver cirrhosis[J].The journal of metabolism,2005,54(4):445-452
[13] Mallat.A,Preaux AM,Blaze Jewskis,et al.Interferon alfa and gamma inhabit prolifera-tion and collagen synthesis of human ito cell in culture[J].Hepatology. 1995, 21(4):1003-1010
[14] Levent Kabasakal, Meral Yuksel, Nursal Gedik,et.al. Hepatic fibrosis in bil-iary-obstructed rats is prevented by Ginkgo biloba treatment [J].World journal of Gastroenterol,2005 ,(35):5444-5449
[15]孙永年,黄视青徐斌等.慢性乙型肝炎患者血清细胞因子与肝纤维化的关系[J].中国医师杂志,2004,6(5):41-43
[16] Jeng Jen-Eing,Tsai Jung-Fa,Chuang Lee-Yea,et,al.tumor necrosis factor—α308.2 polymorphism is associated with advanced hepatic fibrosis and high risk for hepato-cellular carcinoma[J].Neoplasia,2007,9(11):987-992
[17]牛春红,韩得五,刘近春等. TNF-α和IL-10在肝硬化发生中的动态变化的研究[J].中国病理生理杂志,2006;22(12):2467-2473
[18] Amélia Ribeiro de Jesus, Andréa Magalh?es,1Delfin Gonzalez Miranda,et al. Associa-tion of Type 2 Cytokines with Hepatic Fibrosis in Human Schistosoma mansoni In-fection[J]. Infection and immunity,2004 ,72(6):3391-3397
[19]周建华.肝纤维华、肝硬化不同阶段细胞因子的变化[J].中国基层医药,2007, 14(6):954-955
[20] Nammous AH,Pietruczk M,Zukack D,et,al. Structure and biologic function of IFN-gamma[J].Rrzeglad lekarski,2005,62(9):890-893
[21] Yong HA,Bream JH.IFN-gamma :recent advances in understanding regulation of ex-pression, biological function,and clinical application[J].Current top microbiology immunology,2007,316:97-117
[22] Strehl B,Seifert U,Kruger E,et,al.Interferon-gamma,the functional plasticity of the uniquitin-proteasome system, and MHC classⅠantigen processing[J]. Immunology review, 2005,207:19-30
[23] Christophe Cheullard,Carole Eboumbou Moukoko,Nast-Eldin M.A.et al.IFN-γpoly-morphisms(IFN-γ+2109 and IFN-γ+3810) are associated with sever hepatic fibrosis in human hepatic schistosomiasis(schistosoma mansoni) [J].Journal of immunol-ogy,2006,171:5596-5601
[24] Kumar M,Sarin sk.Is cirrhosis of the liver reversible[J].Indian journal of pediat-rics,2007,74(4):393-399
[25] Hammel P,Couvelard A,OTtoole D,Ratouis A,Sauvanet A.Regression of liver fibrosis after billiard drainage in patients with chronic pancreatitis and stenos is of the com-mon bile duct[J].New England journal , 2001,344:418-423
[26] Yue-Hong Huang,Mei-Na Shi,Wei-Da Zheng,et,al.Thereapeutic effect of inter-leukin-10 on CCL4 induced hepatic fibrosis in rats[J]. World journal of Gastroen-terology,2006,12(9):1386-1391
[27] Canbay A, Taimr P, Torok N,et al. Apoptotic body engulfment by a human satellite cell line is profibrogenic[M].Lab Invest,2003,83:655-663
[28]何伟,周伟,沈薇.肝细胞生长因子抗肝纤维化作用及其机制探讨[J].胃肠病学和肝病学杂志,2006,15(6):593-596
[29]尹桂兰.中医药治疗肝纤维化研究近况[J].江苏中医药,2004,25(8):58-60
[30]刘君炎,邓长生,时绍红.银杏叶提取物抗大鼠肝纤维化的实验研究[J].临床消化病杂志,2004,16(1):15-18
[31]杨玲,钱伟,候小华等.莪术提取物对肝纤维化大鼠的血管紧张素Ⅱ及其Ⅰ受体的影响[J].中华肝脏病杂志,2004,14(4):303-305
[32]赵进军,吕志平.白背叶根在肝纤维化动物模型中抗氧化作用的实验研究[J].中药材杂志,2003,25(3):185-187
[33]张万国,胡晋红,蔡溱.桑黄调节细胞因子及其在抗肝纤维化中的意义[J].中国新医药,2003,2(6):19
[34]宋仕玲,龚作炯,张全荣等.中药金三莪方对对实验性肝纤维化大鼠结缔组织生长因子及转化生长因子β1mRNA表达的定位影响[J].解放军医学杂志,2004,(2): 130-133
[35]王胜春,胡咏武,赵辉萍.柴胡与丹参配伍抗大鼠肝纤维化作用的实验研究[J].中国药房,2001,10(10):586-588
[36]陈奇主编.《中药药理实验》[M].贵州人民出版社,1988,158
[37]中华医学会传染病学寄生虫病学分会、肝病学分会联合修订.病毒性肝炎防治方案[J].中华肝脏病杂志,2000,8(6):324-329
[38]杨炼,管小琴,李圆圆.肝硬化和肝癌患者干组织中TGF-β1、TNF-α的表达与HBV感染的关系[J].重庆医科大学学报,2005,30(1):23-26
[39]唐阁,陈文慧.肝纤维化的中医治法研究近况[J].中华中医药杂志,2005,20(6): 361-363
[40] Kiminori Kimura,Kazuki Ando,Hiroo Ohnishi,et,al.Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administrated concanavalin A[J].International immunology,1999,11(9):1491-1500
[41]陈玮,陈维雄,陆允敏等.川芎嗪干预大鼠实验性肝纤维化的研究[J].世界临床药物,2007,28(9):522-525
[42]马周旺,杨俊杰,程卫东等.强肝丸预防四氯化碳诱导的大鼠肝纤维化的实验研究[J].陕西中医,2007,28(11):1561-1563
[43]栾希英,李珂珂,韩兆东.三棱莪术对肝纤维化大鼠IL-1 IL-6 TNF-α的影响.中医中药与免疫,2004,20:834-837
[44] Wang H,Wei W,Wang NP,et,al.melatonin ameliorates Carbon-tetrachloride–induced hepatic fibrogenesis in rats[J].Life Science,2005,77(15):1902-1915
[45] Peng Lv, Shelley Chireyath Paul, Yanjv Xiao,et,al. Effects of Thalidomide on the Ex-pression of Adhesion Molecules in Rat Liver Cirrhosis[J]. Mediators Inflammation. 2006, 2006(4): 932-953
[46]施建平,余小虎,邱夏地.苦参素联合复方丹参对慢性乙型肝炎患者肝纤维化血清学指标、TNF-α和瘦素的影响[J].中国胃肠病学杂志,2007, 12(5):288-290
[47]朱本贵,李昌平,陈霞等.疏肝颗粒对酒精性纤维化的疗效及其机制的实验研究[J].中国中西医结合消化杂志,2006 2,14(1):8-10
[48]孙龙,孙琳琳,杨世忠.肝纤溶颗粒对肝纤维化大鼠血清TNF-α、IL-6水平的影响[J].中国老年学杂质,2006,26(7):1069-1070
[49]王菲张书文.升清降浊丸对免疫性肝损伤模型小鼠细胞因子TNF-α、IL-1、TNF-α、IL-6、IFN-γ的影响[J].世界中西医结合杂志,2007,2(4):210-212
[50]杨小云,观小辉,曾宏等.白细胞介素-18、γ-干扰素与慢性乙型肝炎肝纤维化临床与病理的关系[J].Guangdong Medical Journal,2007 8,28(8):1250-1251
[1]彭彦辉,刘殿武,郝玉斌等.中药方剂对肝纤维化大鼠肝脏ALR基因表达的影响[J].疾病控制杂志,2006,10(4):335-338
[2]张丰,曹苇,王玮等.肝硬化大鼠模型及合并感染时TNF-α和IL-6的基因表达[J].中华肝胆外科杂志,2006,12(4):285-286
[3] Xiao-Zhong Wang,Li-Yuan Zhang,Dan,et,al.Effect of transmitters and interleukin-10 on rat hepatic induced by CCL4[J].Journal of world Gastroenterol, 2003, 9(3):539-543
[4]万昌武,谢汝佳,韩冰等.肝纤维化大鼠肝组织中TGF-β1的表达和细胞外胶原沉积及中药抗肝纤维化治疗的影响[J].贵州医药,2005,29(9):731-734
[5]谢渭芬,林勇.肝纤维化治疗进展[J].实用临床医药杂志,2005,9(7):14-17
[6] Xiang-Wei,MengBao-Rong Chi,Li-Gang,et,al.Expression of interferon-alpha/beta re-ceptor protein in liver of patients with hepatitis C virus-related chronic liver dis-ease[J].The journal of world Gastroenterol,2005,11(25):3962-3965
[7] Henri S,Chevillard C,Mergani A,et al.Cytokine reglantion of periportal fibrosis in humans infected with Schistosomamansoni :IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation disease [J]. Journla of Immunol-ogy ,2002,169:229
[8] Keiding S,Radsherg JH,Becker U,et al .The prognosis of patients with alcoholic liver disease:An international randomized placebo-controlled trial on the effect of sur-vival[J].Journal of Hepatology,1999,20:454-460
[9]华海婴,郭旭光,杨波等.示丹参酮Ⅱ磺酸钠注射液对人肝星状细胞的影响[J].中药药理与临床,2007,23(6):12-14
[10]曾维政肝纤维化治疗策略[J].成都军区医院院报,2003,5(2):23-26
[11]黄古叶,胡振斌,毛德文等.健肝散抗慢性乙型肝炎及其机制研究[J].现代中医药, 2007, 27(6):11-13
[12]胡方平,蒋欣,林勇等.肝纤维化基因治疗新策略[J].中国肝脏病杂志,2007,12(6): 495-497
[13] UEKI KANEKA Y,TSU TSUI H,et al.Hepatocyte growth factor gene therapy of liver cirrhosis in rats[J].淮Nature Mendicine 1999,5(2):226-230
[14] Zhong Z,Froh M,Wheeler MD,et,al.Viral gene delivery of superoxide dismutase at-tenuates experimental cholestasis-induced liver fibrosis in the rats[J]. Gene ther-apy,2002,9:183-191
[15]管军.苦参素治疗乙肝所致肝纤维化临床疗效观察[J].海南医学,2008,19(2):7-8
[16]王怡,薛少礼,薛青等.三七总皂甙对传代肝星型细胞的影响[J].淮南医药,2008, 26(1):1-2
[17]舒建清,王红利,叶国荣等.姜黄素治疗肝纤维化及相关细胞因子的变化研究[J].中药材杂志,2007,30(11):1421-1422
[18]熊振芳,朱清静,杨玲等.莪术提取物对血小板缘性生长因子诱导的HSC细胞内Ca2+和PB-K的影响[J].中西医结合肝病杂志,2007,17,(6):358-360
[19]陈绍兵,陈军华,王玉婷等.甘草酸速对幼龄大鼠实验性肝纤维化的疗效的研究[J].第三军医大学学报,2007,29(23):2261-2263
[20]陈东平,杜慧燕,朱丽萍.大黄对慢性肝炎肝纤维化指标的影响[J].实用中西医结合临床,2007,7(6):87-88
[21]化海婴,李艳瑛,戈士文.川芎嗪抗大鼠免疫损伤性肝纤维化作用及机制研究[J].中药药理与临床,2007,23(5):60-62
[22]刘玉侃,沈薇,张霞.虫草菌丝对实验性肝纤维化的防治作用及其机制研究[J].中国新药与临床杂志,2004,23:139-143
[23]张万国,胡晋红,蔡溱.桑黄调节细胞因子及其在抗肝纤维化中的意义[J].中国新医药,2003,2(6):19
[24]杨错,刑立国,刘玉兰.柴胡对大鼠实验性肝纤维化的预防作用[J].实用药物与临床,2005,8(5):12-14
[25]刘化生,张玲,周景华.柴胡桂枝汤对肝纤维化大鼠转化生长因子β1表达的影响[J].现代中西医结合杂志,2007,16(16):2198-2199
[26]王朝阳,李孝生,尚军洁.川芎嗪与大黄酸联用对大鼠免疫性肝纤维化的治疗作用[J].中国中西医结合消化杂志,2007,15(2):95-98
[27]李蓉,陆伟,赵梦云.黄芪鸡血藤汤对大鼠肝纤维化的预防作用[J].中国中西医结合消化杂志,2007,15(2):99-101
[28]赵红宇,李文斌,灵芝孢子粉抗肝纤维化作用的实验研究[J].中国实用医药2007, 2(5):12-14
[29]晏丹,陈建明,舒赛男等.水蛭桃仁汤对肝纤维化大鼠HSC活化及TGF-β1表达的影响[J].中西医结合肝病杂志,2004,14(1):36
[30]袁强,何岚,陈艺云等.复方鳖甲软肝片对肝纤维化大鼠血管紧张素Ⅱ及其受体mRNA的影响[J].中华中医药杂志,2008,23(2):158-161
[31]张超贤,乔汉臣,杨道坤.三甲益肝冲剂对肝纤维化大鼠结缔组织生长因子表达的影响[J].新乡医学院院报,2008,25(1)9-12