芍药苷对小鼠免疫性肝损伤的作用及其部分机制
|
摘要
肝脏接受门静脉血流,是机体面对酒精、药物毒物、病毒细菌等损伤因素的重要代谢器官。肝脏免疫细胞的组成数量和活化状态与其他免疫组织有着较大的区别,当药物过量(对乙酰氨基酚)、酒精中毒、器官移植(缺血再灌注)、暴发型肝炎、大面积创伤和内毒素休克,往往会引起严重的损伤和炎症反应,在急性期炎症级联反应中,容易诱发严重的弥漫性血管内凝血和多器官功能衰竭而导致死亡。在这些疾病中肝炎是大面积疾患的重要原因,病理表现为肝细胞变性、凋亡、坏死,是多种肝脏疾病共同的起始因素,慢性迁延的损伤使得肝脏逐渐丧失正常的组织结构,逐渐发展成为肝硬化、肝癌。因此,及时的积极的针对多种损伤因素导致的肝脏疾病进行控制将对临床有着重要的意义。
目的:探讨芍药苷(paeoniflorin, Pae)对卡介苗(Bacillus Calmette-Guérin, BCG)加脂多糖(lipopolysaccharide, LPS)诱导的小鼠免疫性肝损伤的作用及其部分机制。
方法:建立BCG+LPS诱导小鼠免疫性肝损伤模型,分光光度法检测血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、一氧化氮(nitric oxide,NO)水平和肝组织中丙二醛(malondiadehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的含量;建立大鼠免疫性肝损伤模型,分光光度法检测血清ALT、AST,肝脏原位灌流分离枯否细胞(kupffer cell,KC)、肝星状细胞(Hepatic Stellate Cellular, HSC),进行共培养,观察KC对HSC增殖的作用,MTT法检测KC培养上清液对HSC增殖的影响和Pae的作用。HE染色法对肝脏组织作病理检查。
结果:(1)Pae(53、105、210 mg·kg-1)和TGP(85 mg·kg-1)灌胃给药能减少免疫性肝损伤小鼠死亡;(2)Pae(53、105、210 mg·kg-1)和TGP(85 mg·kg-1)能降低模型组升高的肝脾指数、降低过高的血清转氨酶水平、减少炎性细胞浸润、减轻肝组织坏死程度和范围、降低肝组织匀浆中升高的MDA水平以及升高SOD、GSH-Px酶活性。(3)Pae 10-7~10-5 mol·L-1作用后能抑制KC培养上清促HSC的增殖的作用,免疫性肝损伤大鼠KC与HSC共培养发现,KC能明显促进HSC的增殖。
结论:Pae对小鼠免疫性肝损伤具有减轻作用;对肝损伤大鼠体外KC促HSC增殖具有抑制作用,其机制可能与抑制脂质过氧化等作用有关。
Liver, which receive blood from portal vein, is the largest metabolic organ in the body. Faced with many insults such as ethanol, drugs, toxic agents, virus and bacteria, liver, which the number and state of activation of immunocyte resident in, is of much more difference compared with other immune organ. Severe inflammatory and injury can be initiated when faced with certain etiological factors, drug overdose, alcoholic intoxication, liver transplantation, fulminant hepatitis, extensive trauma, endotoxemia shock for instance,which leds to high mortality for disseminated intravascular coagulation and for multiple organ dysfunction syndrome during the acute inflammatory phase. The high mobidity of hepatitis is the main reason. Pathology showed hepatocyte degeneration, apoptosis and necrosis that are common causes of various liver diseases. Chronic liver injury can result in lose of its origin structure, gradually develop to cirrhosis and liver cancer. Therefore, positive and timely response to a variety of factors that cause liver damage will have important clinical significance.
OBJECTIVE To investigate the effects and mechanisms of paeoniflorin (Pae) on mice with immunological liver injury (ILI) induced by Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS)
METHODS The model of ILI were induced by BCG plus LPS in mice. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as the concentration of nitric oxide (NO) in serum were assayed by spectrophotometry. Malondiadehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver homogenate were tested by the same method. ILI rats were induced by BCG plus LPS, too. Serum ALT and AST activities were assayed by the method mentioned above. The morphology changes in co-culture were observed on the 7th day. The effects of KC culture medium supplemented with different concentrations of Pae on HSC proliferation were detected by MTT assay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope.
RESULTS (1) Pae (53,105,210 mg·kg-1) and TGP (85 mg·kg-1) ig were able to reduce mortality of ILI mice induced by BCG plus LPS. (2) Liver index, spleen index, and serum transaminase activities (ALT, AST) in ILI mice treated with various dose of Pae were significantly decreased compared with their counterpart in the model group. The area and extent of necrosis as well as the infiltration of inflammatory cells in hepatic tissue sections of ILI mice were attenuated. (3) KC supernatants could promote the HSC proliferation. KC supernatants treated with Pae could decrease the promoting effects of KC on HSC proliferation.
CONCLUSION Paeoniflorin can ameliorate ILI in mice and decrease effects of KC on promoting HSC proliferation. The underlying mechanism may correlated with its ability of free radical scavenging, increasing the activities of SOD and GSH-Px.
目的:探讨芍药苷(paeoniflorin, Pae)对卡介苗(Bacillus Calmette-Guérin, BCG)加脂多糖(lipopolysaccharide, LPS)诱导的小鼠免疫性肝损伤的作用及其部分机制。
方法:建立BCG+LPS诱导小鼠免疫性肝损伤模型,分光光度法检测血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、一氧化氮(nitric oxide,NO)水平和肝组织中丙二醛(malondiadehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的含量;建立大鼠免疫性肝损伤模型,分光光度法检测血清ALT、AST,肝脏原位灌流分离枯否细胞(kupffer cell,KC)、肝星状细胞(Hepatic Stellate Cellular, HSC),进行共培养,观察KC对HSC增殖的作用,MTT法检测KC培养上清液对HSC增殖的影响和Pae的作用。HE染色法对肝脏组织作病理检查。
结果:(1)Pae(53、105、210 mg·kg-1)和TGP(85 mg·kg-1)灌胃给药能减少免疫性肝损伤小鼠死亡;(2)Pae(53、105、210 mg·kg-1)和TGP(85 mg·kg-1)能降低模型组升高的肝脾指数、降低过高的血清转氨酶水平、减少炎性细胞浸润、减轻肝组织坏死程度和范围、降低肝组织匀浆中升高的MDA水平以及升高SOD、GSH-Px酶活性。(3)Pae 10-7~10-5 mol·L-1作用后能抑制KC培养上清促HSC的增殖的作用,免疫性肝损伤大鼠KC与HSC共培养发现,KC能明显促进HSC的增殖。
结论:Pae对小鼠免疫性肝损伤具有减轻作用;对肝损伤大鼠体外KC促HSC增殖具有抑制作用,其机制可能与抑制脂质过氧化等作用有关。
Liver, which receive blood from portal vein, is the largest metabolic organ in the body. Faced with many insults such as ethanol, drugs, toxic agents, virus and bacteria, liver, which the number and state of activation of immunocyte resident in, is of much more difference compared with other immune organ. Severe inflammatory and injury can be initiated when faced with certain etiological factors, drug overdose, alcoholic intoxication, liver transplantation, fulminant hepatitis, extensive trauma, endotoxemia shock for instance,which leds to high mortality for disseminated intravascular coagulation and for multiple organ dysfunction syndrome during the acute inflammatory phase. The high mobidity of hepatitis is the main reason. Pathology showed hepatocyte degeneration, apoptosis and necrosis that are common causes of various liver diseases. Chronic liver injury can result in lose of its origin structure, gradually develop to cirrhosis and liver cancer. Therefore, positive and timely response to a variety of factors that cause liver damage will have important clinical significance.
OBJECTIVE To investigate the effects and mechanisms of paeoniflorin (Pae) on mice with immunological liver injury (ILI) induced by Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS)
METHODS The model of ILI were induced by BCG plus LPS in mice. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as the concentration of nitric oxide (NO) in serum were assayed by spectrophotometry. Malondiadehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver homogenate were tested by the same method. ILI rats were induced by BCG plus LPS, too. Serum ALT and AST activities were assayed by the method mentioned above. The morphology changes in co-culture were observed on the 7th day. The effects of KC culture medium supplemented with different concentrations of Pae on HSC proliferation were detected by MTT assay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope.
RESULTS (1) Pae (53,105,210 mg·kg-1) and TGP (85 mg·kg-1) ig were able to reduce mortality of ILI mice induced by BCG plus LPS. (2) Liver index, spleen index, and serum transaminase activities (ALT, AST) in ILI mice treated with various dose of Pae were significantly decreased compared with their counterpart in the model group. The area and extent of necrosis as well as the infiltration of inflammatory cells in hepatic tissue sections of ILI mice were attenuated. (3) KC supernatants could promote the HSC proliferation. KC supernatants treated with Pae could decrease the promoting effects of KC on HSC proliferation.
CONCLUSION Paeoniflorin can ameliorate ILI in mice and decrease effects of KC on promoting HSC proliferation. The underlying mechanism may correlated with its ability of free radical scavenging, increasing the activities of SOD and GSH-Px.
引文
1 GaoB, Jeong WI, Tian ZG. Liver: An organ with predominant innate immunity. Hepatology, 2008; 47 (2): 729-36.
2邸琳,刘新宇,常福红,王永生,张群功.芍药甘草汤对小鼠急性肝损伤的保护作用.中药药理与临床, 2007; 23 (6): 4-5.
3王华,魏伟,岳莉,汪倪萍,桂双英,吴丽,孙妩弋,徐叔云.白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用.中国药理学通报, 2004; 20 (8): 875-78.
4詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报, 2006; 41 (6): 664-66.
5路景涛,孙妩弋,刘浩,李响,魏伟.白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响.中国药理学通报, 2008; 24 (005): 588-92.
6李瑞麟,马勇,魏伟,叶根深,陈文笔,严家春.白芍总苷治疗四氯化碳致大鼠肝纤维化的作用与其影响肝星状细胞功能的关系.中国新药杂志, 2007; 16 (009): 685-89.
7魏伟,刘家骏,刘家琴,李旭,徐叔云.白芍总苷对乙型肝炎的治疗作用及其前景.中国药理学通报, 2000; 16 (5): 596-7.
8 Liu D, Wei W, Song L. Protective effect of paeoniflorin on immunological liver injury induced by Bacillus Calmette-Guérin plus lipopolysaccharide: modulation of tumor necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
9 Chu D, Li C, Wu Q, Shen J. Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice. Frontiers of Medicine in China, 2008; 2 (2): 154-65.
10邱英锋,缪晓辉,王俊学,张瑞祺,蔡雄,倪武.卡介苗加脂多糖建立大鼠急性免疫性肝损伤模型的研究.实验动物科学与管理, 2004; 21 (003): 15-19.
11宋少刚,杨雁.大鼠肝贮脂细胞,枯否细胞的同时分离和培养.中国临床药理学与治疗学, 2000; 5 (4): 351-53.
12 Kim EM, Jeong HJ, Park IK, Cho CS, Kim CG, Bom H-S. Hepatocyte-Targeted Nuclear Imaging Using 99mTc-Galactosylated Chitosan: Conjugation, Targeting, and Biodistribution. J Nucl Med, 2005; 46 (1): 141-45.
13 Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, et al. Impaired liver regeneration in mice by lipopolysaccharide via TNF-α/kallikrein–mediated activation of latent TGF-β. Gastroenterology, 2002; 123 (1): 352-64.
14 Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver International, 2006; 26 (10): 1175-86.
15 Reynaert H, Thompson MG, Thomas T, Geerts A. Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. British Medical Journal, 2002; 50 (4): 571.
16 Zhang X, Yu W, Gao L, Wei K, Ju J, Xu J. Effects of lipopolysaccharides stimulated Kupffer cells on activation of rat hepatic stellate cells. World Journal of Gastroenterology, 2004; 10 (4): 610-13.
17邵芙蓉,魏伟,刘浩,孙妩弋,李响.不同方法提取的复方芍芪多苷对小鼠免疫性肝损伤保护作用比较.安徽中医学院学报, 2007; 26 (005): 21-24.
18杨秀芬,庞紫妤,周芳,郭菁菁,王乃平.灯盏乙素对小鼠免疫性肝损伤的保护作用.时珍国医国药, 2007; 5 (4).
19 Nakashima H, Kinoshita M, Nakashima M, Habu Y, Shono S, Uchida T, Shinomiya N, Seki S. Superoxide produced by Kupffer cells is an essential effector in concanavalin A-induced hepatitis in mice. Hepatology, 2008; 48 (6): 1979-88.
20 Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian ZG, Nguyen VA,Gao B. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. Journal of Clinical Investigation, 2002; 110 (10): 1503-13.
21梁萍,薄爱华.苦参碱抗免疫性肝损伤机制的研究.世界华人消化杂志, 1999; 7 (002): 104-08.
22杨天健,刘耕陶. 16种药物对卡介苗加脂多糖引起小鼠免疫性肝损伤的作用.中国药理学报, 1997; 18 (002): 185-88.
23 Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med, 2008; 205 (1): 233-44.
24 Wang H, Wei W, Wang NP, Wu CY, Yan SX, Yue L, Zhang LL, Xu SY. Effects of total glucosides of peony on immunological hepatic fibrosis in rats. World Journal of Gastroenterology, 2005; 11 (14): 2124-29.
25 Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus calmette-guerin plus lipopolysaccharide: modulation of tumour necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
26刘道芳Toll样受体4介导BCG/LPS诱导免疫性肝损伤的机制及芍药苷的作用.安徽医科大学博士论文, 2006;78-9.
27刘烨.白芍总甙负调节大腹腔巨噬细胞诱生TNF的定量分析.数理医药学杂志, 1998; 11 (001): 1-2.
28葛志东,魏伟.芍药甙和去芍药甙白芍总甙对佐剂性关节炎大鼠脾淋巴细胞产生白介素2的影响.安徽医科大学学报, 1996; 31 (001): 4-6.
29 Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-κB activation through modulation of IκBαand enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomedicine & Pharmacotherapy, 2008; 62 (9): 659-66.
30 Tsai T, Wu S, Liu Y, Wu A, Tsai Y. Inhibitory action of L-type Ca2+ current bypaeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. European Journal of Pharmacology, 2005; 523 (1-3): 16-24.
31王晓玉,魏伟,唐丽琴,吴虹,杨宇清,陈尹.芍药苷对佐剂性关节炎大鼠腹腔巨噬细胞吞噬功能及其产生细胞因子的影响.安徽医科大学学报, 2007; 42 (2): 189-92.
32陈尹,魏伟,吴虹,张玲玲,陈镜宇.芍药苷对佐剂性关节炎大鼠脾细胞产生抗体和cAMP水平的影响.药学学报, 2007; 42 (11): 1147-51.
33 Ofenstein J, Heidemann S, Juett A, Sarnaik A. Endotoxin inhibits heat induced HSP-70 in rats. Critical Care Medicine, 1998; 26 (Suppl 1): A138.
34 Hotchkiss R, Nunnally I, Lindquist S, Taulien J, Perdrizet G, Karl I. Hyperthermia protects mice against the lethal effects of endotoxin. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 1993; 265 (6): 1447-57.
35 Lotte W, Femke B, Ruurd van der Z, Elles Klein K, Josée W, Willem van E. Cell stress induced HSP are targets of regulatory T cells: A role for HSP inducing compounds as anti-inflammatory immuno-modulators? FEBS letters, 2007; 581 (19): 3716-22.
36 Ye J, Duan H, Yang X, Yan W, Zheng X. Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo. Planta medica, 2001; 67 (8): 766.
37 Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ. Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. The International Journal of Biochemistry & Cell Biology, 2007; 39 (2): 426-38.
38 Lee S, Kwon Y, Son K, Kim H, Heo M. Antioxidative constituents from Paeonia lactiflora. Archives of Pharmacal Research, 2005; 28 (7): 775-83.
39 Liu H, Wei W, Li X. Celecoxib exacerbates hepatic fibrosis and induceshepatocellular necrosis in rats treated with porcine serum. Prostaglandins & Other Lipid Mediators, 2009; 88 (3-4): 63-7.
40 Ikejima K, Enomoto N, Seabra V, Ikejima A, Brenner D, Thurman R. Pronase destroys the lipopolysaccharide receptor CD14 on Kupffer cells. American Journal of Physiology Gastrointestinal and Liver Physiology, 1999; 276 (3): 591-98.
41 Bellezzo JM, Britton RS, Bacon BR, Fox ES. LPS-mediated NF-κB activation in rat Kupffer cells can be induced independently of CD14. American Journal of Physiology Gastrointestinal and Liver Physiology, 1996; 270 (6): G956-61.
42 Yang J, Gallagher S, Haines K, Epling-Burnette P, Bai F, Gower W, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
43 Strain A. Isolated hepatocytes: use in experimental and clinical hepatology. British Medical Journal, 1994; 35 (4): 433-36.
44 Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44: 1487-501.
45 Yang J, Gallagher SF, Haines K, Epling-Burnette PK, Bai F, Gower WR, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
46 Bataller R, Brenner DA. Liver fibrosis. J Clin Invest, 2005; 115 (2): 209-18.
47 Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF. TLR4 enhances TGF-βsignaling and hepatic fibrosis. Nature Medicine, 2007; 13 (11): 1324-32.
48 Natalia Nieto. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44 (6): 1487-501.
1 Xin Hou RZ, Haiming Wei, Rui Sun, Zhigang Tian. NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis. Hepatology, 2009; 49 (3): 940-49.
2 Feng Zhou MNA, Paul L. Beck, Tai Le, Cory M. Hogaboam, Mark G. Swain. CD154-CD40 interactions drive hepatocyte apoptosis in murine fulminant hepatitis. Hepatology, 2005; 42 (2): 372-80.
3 Yang J, Gallagher S, Haines K, Epling-Burnette PK, Bai F, Gower WR, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
4 Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian ZG, Nguyen VA, Gao B. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. Journal of Clinical Investigation, 2002; 110 (10): 1503-13.
5 Kim WH, Hong F, Radaeva S, Jaruga B, Fan S, Gao B. STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 2003; 285 (4): G761-68.
6 Tsuji H, Mukaida N, Harada A, Kaneko S, Matsushita E, Nakanuma Y, Tagawa Y, Iwakura Y, Kobayashi K, Matsushima K. Alleviation of Lipopolysaccharide-Induced Acute Liver Injury in Propionibacterium acnes-Primed IFN-γ-Deficient Mice by a Concomitant Reduction of TNF-α, IL-12, and IL-18 Production. Journal of Immunolology, 1999; 162 (2): 1049-55.
7 Nakashima H, Kinoshita M, Nakashima M, Habu Y, Shono S, Uchida T, Shinomiya N, Seki S. Superoxide produced by Kupffer cells is an essential effector in concanavalin A-induced hepatitis in mice. Hepatology, 2008; 48 (6): 1979-88.
8梁萍,薄爱华.苦参碱抗免疫性肝损伤机制的研究.世界华人消化杂志, 1999; 7 (002): 104-08.
9 Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44 (6): 1487-501.
10 Lalor PF, Shields P, Grant AJ, Adams DH. Recruitment of lymphocytes to the human liver. Immunology and Cell Biology, 2002; 80 (1): 52-64.
11 Bremer C, Bradford BU, Hunt KJ, Knecht KT, Connor HD, Mason RP, Thurman RG. Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 1994; 267 (4): G630-36.
12 Bilzer M, Jaeschke H, Vollmar AM, Paumgartner G, Gerbes AL. Prevention of Kupffer cell-induced oxidant injury in rat liver by atrial natriuretic peptide. American Journal of Physiology - Gastrointestinal and Liver Physiology, 1999; 276 (5): G1137-44.
13 Titos E, Clària J, PlanagumàA, López-Parra M, González-Périz A, Gaya J, Miquel R, Arroyo V, Rodés J. Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells. Journal of Leukocyte Biology, 2005; 78 (4): 871-78.
14 Tomiyama K, Ikeda A, Ueki S, Nakao A, Stolz DB, Koike Y, Afrazi A, Gandhi C, Tokita D, Geller DA, Murase N. Inhibition of Kupffer cell-mediated earlyproinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats. Hepatology, 2008; 48 (5): 1608-20.
15 Polakos NK, Cornejo JC, Murray DA, Wright KO, Treanor JJ, Crispe IN, Topham DJ, Pierce RH. Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection. American Journal of Pathology, 2006; 168 (4): 1169-78.
16 Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, Pierce RH, Crispe IN. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood, 2007; 110 (12): 4077-85.
17 Terpstra V, van Berkel TJC. Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice. Blood, 2000; 95 (6): 2157-63.
18 van Egmond M, van Garderen E, van Spriel AB, Damen CA, van Amersfoort ES, van Zandbergen G, van Hattum J, Kuiper J, van de Winkel JGJ. FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity. Nature Medicine, 2000; 6 (6): 680-85.
19 Helmy KY, Katschke KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van lookeren Campagne M. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell, 2006; 124 (5): 915-27.
20 Hildebrand F, Hubbard WJ, Choudhry MA, Frink M, Pape HC, Kunkel SL, Chaudry IH. Kupffer Cells and Their Mediators: The Culprits in Producing Distant Organ Damage after Trauma-Hemorrhage. American Journal of Pathology, 2006; 169 (3): 784-94.
21 Sleyster EC, Knook DL. Relation between localization and function of rat liver Kupffer cells. Laboratory Investigation, 1982; 47 (5): 484-90.
22 Bouwens L, Baekeland M, De Zanger R, Wisse E. Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liver. Hepatology, 1986; 6 (4): 718-22.
23 Bykov I, Ylipaasto P, Eerola L, Lindros KO. Phagocytosis and LPS-stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region. Scandinavian Journal of Gastroenterology, 2003; 38 (12): 1256-61.
24 Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G. Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood, 1996; 87 (11): 4568-80.
25 Mathison JC, Ulevitch RJ. The clearance, tissue distribution, and cellular localization of intravenously injected lipopolysaccharide in rabbits. The Journal of Immunology, 1979; 123 (5): 2133.
26 van der Laan LJW, D?pp EA, Haworth R, Pikkarainen T, Kangas M, Elomaa O, Dijkstra CD, Gordon S, Tryggvason K, Kraal G. Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo. The Journal of Immunology, 1999; 162 (2): 939-47.
27 Toshiyuki Kitazawa TT, Hideto Kawaratani, Hiroshi Fukui,. Therapeutic approach to regulate innate immune response by Toll-like receptor 4 antagonist E5564 in rats with D-galactosamine-induced acute severe liver injury. Journal of Gastroenterology and Hepatology, 2009; doi:10.1111/j.1440-1746.2008.05770.x.
28 Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. TLR-dependent cross talk between human Kupffer cells and NK cells. Journal of Experimental Medicine, 2008; 205 (1): 233-44.
29 Matthew Giannandrea RHP, Ian Nicholas Crispe. Indirect action of tumor necrosis factor-αin liver injury during the CD8+ T cell response to an adeno-associated virus vector in mice. Hepatology, 2009; doi:10.1002/hep22869.
30 Ahmad N, Chen LC, Gordon MA, Laskin JD, Laskin DL. Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. Journal of Leukocyte Biolology, 2002; 71 (6): 1005-11.
31 Casado M, Callejas NA, Rodrigo J, Zhao X, Dey SK, BoscáL, Martín-Sanz P. Contribution of cyclooxygenase-2 to liver regeneration after partial hepatectomy. FASEB Journal, 2001; 15 (11):2016-8.
32 Souto EO, Miyoshi H, Dubois RN, Gores GJ. Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats. American Journal of Physiology - Gastrointestinal and Liver Physiology, 2001; 280 (5): G805-11.
33 Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil RW, Coito AJ. Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury. Journal of Immunology, 2008; 180 (3): 1843-53.
34 Han C, Li G, Lim K, DeFrances MC, Gandhi CR, Wu T. Transgenic Expression of Cyclooxygenase-2 in Hepatocytes Accelerates Endotoxin-Induced Acute Liver Failure. Journal of Immunology, 2008; 181 (11): 8027-35.
35 Perlik V, Li Z, Goorha S, Ballou LR, Blatteis CM. LPS-activated complement, not LPS per se, triggers the early release of PGE2 by Kupffer cells. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2005; 289 (2): R332-39.
36 Liu H, Wei W, Li X. Celecoxib exacerbates hepatic fibrosis and induces hepatocellular necrosis in rats treated with porcine serum. Prostaglandins & Other Lipid Mediators, 2009; 88 (3-4): 63-7.
37 Ito H, Ando K, Ishikawa T, Saito K, Takemura M, Imawari M, Moriwaki H, Seishima M. Role of TNF-αProduced by Nonantigen-Specific Cells in a Fulminant Hepatitis Mouse Model. Journal of Immunology, 2009; 182 (1): 391-97.
38 Mark JC. Another way for NADPH oxidase to send a signal for liver injury. Gastroenterology, 2005; 129 (6): 2110-13.
39 Samuele DM, Ramón B, David AB. NADPH Oxidase in the Liver: Defensive, Offensive, or Fibrogenic? Gastroenterology, 2006; 131 (1): 272-75.
40 Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase. Hepatology, 2002; 35 (2): 289-98.
41 Yang CY, Kuo TH, Ting LP. Human hepatitis B viral e antigen interacts with cellular interleukin-1 receptor accessory protein and triggers interleukin-1 response. Journal of Biological Chemistry, 2006; 281 (45): 34525-36.
42 Tian Z, Shen X, Feng H, Gao B. IL-1βAttenuates IFN-αβ-induced antiviral activity and STAT1 activation in the liver: involvement of proteasome-dependent pathway. Journal of Immunology, 2000; 165 (7): 3959-65.
43 Bohlinger I, Leist M, Barsig J, Uhlig T, Tiegs G, Wendel A. Interleukin-1 and nitric oxide protect against tumor necrosis factor-induced liver injury through distinct pathways. Hepatology, 1995; 22 (6): 1829-37.
44 Harada H, Wakabayashi G, Takayanagi A, Shimazu M, Matsumoto K, Obara H, Shimizu N, Kitajima M. Transfer of the interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury. Transplantation, 2002; 74 (10): 1434-41.
45 Sun R, Tian ZG, Kulkarni S, Gao B. IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells in CD4+ T Cell and STAT3 dependent manners. Journal of Immunology, 2004; 172 (9): 5648-55.
46 Bourdi M, Eiras DP, Holt MP, Webster MR, Reilly TP, Welch KD, Pohl LR. Role of IL-6 in an IL-10 and IL-4 double knockout mouse model uniquely susceptible to acetaminophen-induced liver injury. Chemical Research Toxicology, 2007; 20 (2): 208-16.
47 Kovalovich K, Li W, DeAngelis R, Greenbaum LE, Ciliberto G, Taub R. Interleukin-6 Protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. Journal of Biological Chemistry, 2001; 276 (28): 26605-13.
48 Galun E, Zeira E, Pappo O, Peters M, Rose-John S. Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury. FASEB Journal, 2000; 14 (13): 1979-87.
49 Herrero C, Hu XY, Li WP, Samuels S, Sharif MN, Kotenko S, Ivashkiv LB. Reprogramming of IL-10 Activity and Signaling by IFN-γ. Journal of Immunology, 2003; 171 (10): 5034-41.
50 Bliss SK, Bliss SP, Beiting DP, Alcaraz A, Appleton JA. IL-10 Regulates Movement of Intestinally Derived CD4+ T Cells to the Liver. Journal of Immunology, 2007; 178 (12): 7974-83.
51 Dinant S, Vetel?inen RL, Florquin S, van Vliet AK, van Gulik TM. IL-10 attenuates hepatic I/R injury and promotes hepatocyte proliferation. Journal of Surgical Research, 2007; 141 (2): 176-82.
52 Tanaka Y, Takahashi A, Watanabe K, Takayama K, Yahata T, Habu S, Nishimura T. A pivotal role of IL-12 in Th1-dependent mouse liver injury. International Immunology, 1996; 8 (4): 569-76.
53 Margenthaler JA, Ku G, Flye MW. Interleukin-12 regulates natural killer cell-dependent Propionibacterium acnes-primed, lipopolysaccharide-induced liver injury. Hepatology Research, 2008; 38 (2): 183-93.
54 Zhu R, Diem S, Araujo LM, Aumeunier A, Denizeau J, Philadelphe E. The pro-Th1 cytokine IL-12 enhances IL-4 production by invariant NKT cells: relevance for T cell-mediated hepatitis. Journal of immunology, 2007; 178 (9): 5435-42.
55 Adachi K, Tsutsui H, Kashiwamura SI, Seki E, Nakano H, Takeuchi O, Takeda K, Okumura K, Kaer LV, Okamura H, Akira S, Nakanishi K. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. Journal of Immunology, 2001; 167 (10): 5928-34.
56 Yajima T, Nishimura H, Saito K, Kuwano H, Yoshikai Y. Overexpression of Interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with mycobacterium bovis Bacillus Calmette-Guérin. Infection and Immunity, 2004; 72 (7): 3855-62.
57 Finotto S, Siebler J, Hausding M, Schipp M, Wirtz S, Klein S, Protschka M, Doganci A, Lehr HA, Trautwein C, Khosravi-Fahr R, Strand D, Lohse A, Galle PR, Blessing M, Neurath MF. Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo. Gut, 2004; 53 (3): 392-400.
58 Faggioni R, Cattley RC, Guo J, Flores S, Brown H, Qi M, Yin SM, Hill D, Scully S, Chen C, Brankow D, Lewis J, Baikalov C, Yamane H, Meng T, Martin F, Hu S, Boone T, Senaldi G. IL-18-binding protein protects against lipopolysaccharide induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice. Journal of Immunology, 2001; 167 (10): 5913-20.
59 Lin W, Zhang J, Hu Z, Qian D. Inhibitory effect of matrine on lipopolysacchride-induced tumor necrosis factor and interleukin-6 production from rat Kupffer cells. Yao Xue Xue Bao, 1997; 32 (2): 93-6.
60 Zhu X, Qiu Y, Shi M, Ding Y. Matrine Protects Sinusoidal Endothelial Cells From Cold Ischemia and Reperfusion Injury in Rat Orthotopic Liver Transplantation. Annals of Clinical Laboratory Science, 2003; 33 (2): 216-25.
61李常青,刘丽丽,莫传伟,黄玲.苦参碱对Con A性肝损伤小鼠IFN释放及肝组织病理改变的影响.世界华人消化杂志, 2005; 13 (005): 640-43.
62赵丽娟,李红,杨世杰.黄芪注射液对d—半乳糖胺所致小鼠急性肝损伤的保护作用.吉林大学学报:医学版, 2003; 29 (3): 280-82.
63侯敬申,潘运龙,覃莉,赵莉.黄芪注射液对刀豆蛋白诱导的小鼠肝脏损伤的保护作用.中华实用中西医杂志, 2005; 18 (20): 1287-89.
64刘印忠,马德禄,高建华,康毅.黄芪注射液对小鼠免疫性肝损伤的保护作用.天津医科大学学报, 2004; 10 (2): 190-91.
65程梦琳,陈金和,吴基良,罗德生,汪素涵.黄芪注射液对大鼠肠缺血再灌注肝损伤NO、SOD的影响.华中医学杂志, 2004; 28 (1): 15-16.
66欧阳雁玲,张明升.黄芪注射液对四氯化碳损伤小鼠肝的保护作用.太原科技, 2002; 3: 26-27.
67汪德清,丁保国,等.黄芪总黄酮对扑热息痛所致小鼠肝损伤防护作用的研究.中国中药杂志, 2001; 26 (7): 483-86.
68杨雁,陈敏珠.黄芪总甙及其单体抗肝损伤作用的机理.中国药理学会通讯, 2001; 18 (4): 10-11.
69路景涛,杨雁,魏伟,陈敏珠.黄芪多部位组合对化学性及免疫性肝损伤小鼠的保护作用.中国中医药信息杂志, 2008; 15 (1): 32-34.
70路景涛,杨雁,陈敏珠.黄芪多糖对细菌脂多糖诱导大鼠腹腔巨噬细胞释放TNF-α, NO及IL-1的影响.安徽医科大学学报, 2004; 39 (002): 139-41.
71路景涛,陈敏珠.复方黄芪提取物对细菌脂多糖诱导大鼠腹腔巨噬细胞分泌TNF-α, NO及IL-1的影响.安徽医药, 2006; 10 (005): 330-31.
72刘协,顾呈华,胡启之,潘玉英.甘草甜素脂质体对小鼠急性酒精性肝损伤的保护作用.中国临床康复, 2004; 8 (36): 8260-61.
73刘东,蒋毅萍,陈志良.甘草甜素与苦参碱联合用药对四氯化碳所致小鼠急、慢性肝损伤的保护作用.中药材, 2007; 30 (5): 581-83.
74王根生,韩哲武.甘草类黄酮对乙醇所致小鼠肝脏脶伤的影响.中国药理学通报, 1993; 9 (4): 271-73.
75王根生,韩哲武.甘草类黄酮对四氯化碳致小鼠急性肝损伤的影响.药学学报, 1993; 28 (8): 572-76.
76尹龙武,吕晓君,杨静,李颖,宛菁.异甘草素对小鼠免疫性肝损伤的保护作用及其机制.中国药理通讯, 2007; 24 (3): 37-37.
77陈冬裕.甘草酸类药物在药物性肝损伤中的应用.海峡药学, 2007; 19 (8): 6-9.
78鲍启德,杨兰兰,王利,崔东来.异甘草酸镁对CCl4诱导小鼠急性肝损伤的保护作用.世界华人消化杂志, 2008; 16 (9): 1004-07.
79吴希美,周汉良,等.小柴胡冲剂对乙酰氨基酚肝损伤的保护作用及机理研究.中药药理与临床, 1997; 13 (6): 8-10.
80邵鸿娥,邵宏元.小柴胡汤加味对小鼠实验性肝损伤的保护作用.山西医药杂志, 1995; 24 (3): 171-72.
81杨错,刘玉兰,张红梅.柴胡乳剂对急性化学性肝损伤的保护作用.沈阳药科大学学报, 2006; 23 (2): 105-08.
82谢斌,张奉学,杨子峰,刘妮.加味小柴胡汤对刀豆蛋白A所致肝损伤的保护作用.中国热带医学, 2006; 6 (4): 572-73.
83李荣萍,任成山,赵晓宴.水飞蓟宾对急性肝损伤中肝细胞胀亡的影响及其机制.中国中西医结合急救杂志, 2006; 13 (4): 202-05.
84王伟,黄爔乐,利红宇,陈一岳.水飞蓟宾对四氯化碳所致肝损伤的治疗与预防作用.广东药学院学报, 2005; 21 (5): 565-67.
85薛洪源,侯艳宁,刘会虑,陈静,曹颖.水飞蓟宾胶囊对异烟肼和利福平肝损害小鼠的保护作用.中成药, 2003; 25 (4): 307-10.
86谭海荣,吴谦,潘竞锵,肖柳英,韩超,林洁茹,郑琳颖,李博萍.水飞蓟宾对抗大鼠酒精性脂肪肝作用及机制.中国临床药理学与治疗学, 2004; 9 (7): 803-06.
87邸琳,刘新宇,常福红,王永生,张群功.芍药甘草汤对小鼠急性肝损伤的保护作用.中药药理与临床, 2007; 23 (6): 4-5.
88詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报, 2006; 41 (6): 664-66.
89王华,魏伟,岳莉,汪倪萍,桂双英,吴丽,孙妩弋,徐叔云.白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用.中国药理学通报, 2004; 20 (8): 875-78.
90路景涛,孙妩弋,刘浩,李响,魏伟.白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响.中国药理学通报, 2008; 24 (5): 588-92.
91魏伟,刘家骏.白芍总苷对乙型肝炎的治疗作用及其前景.中国药理学通报, 2000; 16 (5): 597-98.
92 Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus calmette-guérin plus lipopolysaccharide: modulation of tumour necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
93 Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-κB activation through modulation of IκBαand enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomedicine & Pharmacotherapy, 2008; 62 (9): 659-66.
94 Tsai T, Wu S, Liu Y, Wu A, Tsai Y. Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. European Journal of Pharmacology, 2005; 523 (1-3): 16-24.
95 Ye J, Duan H, Yang X, Yan W, Zheng X. Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo. Planta medica, 2001; 67 (8): 766.
96王晓玉,魏伟,唐丽琴,吴虹,杨宇清,陈尹.芍药苷对佐剂性关节炎大鼠腹腔巨噬细胞吞噬功能及其产生细胞因子的影响.安徽医科大学学报, 2007; 42 (2): 189-92.
97陈尹,魏伟,吴虹,张玲玲,陈镜宇.芍药苷对佐剂性关节炎大鼠脾细胞产生抗体和cAMP水平的影响.药学学报, 2007; 42 (11): 1147-51.
98 Chu D, Li C, Wu Q, Shen J. Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice. Frontiers of Medicine in China, 2008; 2 (2): 154-65.
99 Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ. Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. The International Journal of Biochemistry & Cell Biology, 2007; 39 (2): 426-38.
100刘平.中草药的肝损伤问题.中华肝脏病杂志, 2004; 12 (4): 243-43.
2邸琳,刘新宇,常福红,王永生,张群功.芍药甘草汤对小鼠急性肝损伤的保护作用.中药药理与临床, 2007; 23 (6): 4-5.
3王华,魏伟,岳莉,汪倪萍,桂双英,吴丽,孙妩弋,徐叔云.白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用.中国药理学通报, 2004; 20 (8): 875-78.
4詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报, 2006; 41 (6): 664-66.
5路景涛,孙妩弋,刘浩,李响,魏伟.白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响.中国药理学通报, 2008; 24 (005): 588-92.
6李瑞麟,马勇,魏伟,叶根深,陈文笔,严家春.白芍总苷治疗四氯化碳致大鼠肝纤维化的作用与其影响肝星状细胞功能的关系.中国新药杂志, 2007; 16 (009): 685-89.
7魏伟,刘家骏,刘家琴,李旭,徐叔云.白芍总苷对乙型肝炎的治疗作用及其前景.中国药理学通报, 2000; 16 (5): 596-7.
8 Liu D, Wei W, Song L. Protective effect of paeoniflorin on immunological liver injury induced by Bacillus Calmette-Guérin plus lipopolysaccharide: modulation of tumor necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
9 Chu D, Li C, Wu Q, Shen J. Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice. Frontiers of Medicine in China, 2008; 2 (2): 154-65.
10邱英锋,缪晓辉,王俊学,张瑞祺,蔡雄,倪武.卡介苗加脂多糖建立大鼠急性免疫性肝损伤模型的研究.实验动物科学与管理, 2004; 21 (003): 15-19.
11宋少刚,杨雁.大鼠肝贮脂细胞,枯否细胞的同时分离和培养.中国临床药理学与治疗学, 2000; 5 (4): 351-53.
12 Kim EM, Jeong HJ, Park IK, Cho CS, Kim CG, Bom H-S. Hepatocyte-Targeted Nuclear Imaging Using 99mTc-Galactosylated Chitosan: Conjugation, Targeting, and Biodistribution. J Nucl Med, 2005; 46 (1): 141-45.
13 Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, et al. Impaired liver regeneration in mice by lipopolysaccharide via TNF-α/kallikrein–mediated activation of latent TGF-β. Gastroenterology, 2002; 123 (1): 352-64.
14 Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver International, 2006; 26 (10): 1175-86.
15 Reynaert H, Thompson MG, Thomas T, Geerts A. Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. British Medical Journal, 2002; 50 (4): 571.
16 Zhang X, Yu W, Gao L, Wei K, Ju J, Xu J. Effects of lipopolysaccharides stimulated Kupffer cells on activation of rat hepatic stellate cells. World Journal of Gastroenterology, 2004; 10 (4): 610-13.
17邵芙蓉,魏伟,刘浩,孙妩弋,李响.不同方法提取的复方芍芪多苷对小鼠免疫性肝损伤保护作用比较.安徽中医学院学报, 2007; 26 (005): 21-24.
18杨秀芬,庞紫妤,周芳,郭菁菁,王乃平.灯盏乙素对小鼠免疫性肝损伤的保护作用.时珍国医国药, 2007; 5 (4).
19 Nakashima H, Kinoshita M, Nakashima M, Habu Y, Shono S, Uchida T, Shinomiya N, Seki S. Superoxide produced by Kupffer cells is an essential effector in concanavalin A-induced hepatitis in mice. Hepatology, 2008; 48 (6): 1979-88.
20 Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian ZG, Nguyen VA,Gao B. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. Journal of Clinical Investigation, 2002; 110 (10): 1503-13.
21梁萍,薄爱华.苦参碱抗免疫性肝损伤机制的研究.世界华人消化杂志, 1999; 7 (002): 104-08.
22杨天健,刘耕陶. 16种药物对卡介苗加脂多糖引起小鼠免疫性肝损伤的作用.中国药理学报, 1997; 18 (002): 185-88.
23 Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med, 2008; 205 (1): 233-44.
24 Wang H, Wei W, Wang NP, Wu CY, Yan SX, Yue L, Zhang LL, Xu SY. Effects of total glucosides of peony on immunological hepatic fibrosis in rats. World Journal of Gastroenterology, 2005; 11 (14): 2124-29.
25 Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus calmette-guerin plus lipopolysaccharide: modulation of tumour necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
26刘道芳Toll样受体4介导BCG/LPS诱导免疫性肝损伤的机制及芍药苷的作用.安徽医科大学博士论文, 2006;78-9.
27刘烨.白芍总甙负调节大腹腔巨噬细胞诱生TNF的定量分析.数理医药学杂志, 1998; 11 (001): 1-2.
28葛志东,魏伟.芍药甙和去芍药甙白芍总甙对佐剂性关节炎大鼠脾淋巴细胞产生白介素2的影响.安徽医科大学学报, 1996; 31 (001): 4-6.
29 Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-κB activation through modulation of IκBαand enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomedicine & Pharmacotherapy, 2008; 62 (9): 659-66.
30 Tsai T, Wu S, Liu Y, Wu A, Tsai Y. Inhibitory action of L-type Ca2+ current bypaeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. European Journal of Pharmacology, 2005; 523 (1-3): 16-24.
31王晓玉,魏伟,唐丽琴,吴虹,杨宇清,陈尹.芍药苷对佐剂性关节炎大鼠腹腔巨噬细胞吞噬功能及其产生细胞因子的影响.安徽医科大学学报, 2007; 42 (2): 189-92.
32陈尹,魏伟,吴虹,张玲玲,陈镜宇.芍药苷对佐剂性关节炎大鼠脾细胞产生抗体和cAMP水平的影响.药学学报, 2007; 42 (11): 1147-51.
33 Ofenstein J, Heidemann S, Juett A, Sarnaik A. Endotoxin inhibits heat induced HSP-70 in rats. Critical Care Medicine, 1998; 26 (Suppl 1): A138.
34 Hotchkiss R, Nunnally I, Lindquist S, Taulien J, Perdrizet G, Karl I. Hyperthermia protects mice against the lethal effects of endotoxin. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 1993; 265 (6): 1447-57.
35 Lotte W, Femke B, Ruurd van der Z, Elles Klein K, Josée W, Willem van E. Cell stress induced HSP are targets of regulatory T cells: A role for HSP inducing compounds as anti-inflammatory immuno-modulators? FEBS letters, 2007; 581 (19): 3716-22.
36 Ye J, Duan H, Yang X, Yan W, Zheng X. Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo. Planta medica, 2001; 67 (8): 766.
37 Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ. Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. The International Journal of Biochemistry & Cell Biology, 2007; 39 (2): 426-38.
38 Lee S, Kwon Y, Son K, Kim H, Heo M. Antioxidative constituents from Paeonia lactiflora. Archives of Pharmacal Research, 2005; 28 (7): 775-83.
39 Liu H, Wei W, Li X. Celecoxib exacerbates hepatic fibrosis and induceshepatocellular necrosis in rats treated with porcine serum. Prostaglandins & Other Lipid Mediators, 2009; 88 (3-4): 63-7.
40 Ikejima K, Enomoto N, Seabra V, Ikejima A, Brenner D, Thurman R. Pronase destroys the lipopolysaccharide receptor CD14 on Kupffer cells. American Journal of Physiology Gastrointestinal and Liver Physiology, 1999; 276 (3): 591-98.
41 Bellezzo JM, Britton RS, Bacon BR, Fox ES. LPS-mediated NF-κB activation in rat Kupffer cells can be induced independently of CD14. American Journal of Physiology Gastrointestinal and Liver Physiology, 1996; 270 (6): G956-61.
42 Yang J, Gallagher S, Haines K, Epling-Burnette P, Bai F, Gower W, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
43 Strain A. Isolated hepatocytes: use in experimental and clinical hepatology. British Medical Journal, 1994; 35 (4): 433-36.
44 Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44: 1487-501.
45 Yang J, Gallagher SF, Haines K, Epling-Burnette PK, Bai F, Gower WR, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
46 Bataller R, Brenner DA. Liver fibrosis. J Clin Invest, 2005; 115 (2): 209-18.
47 Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF. TLR4 enhances TGF-βsignaling and hepatic fibrosis. Nature Medicine, 2007; 13 (11): 1324-32.
48 Natalia Nieto. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44 (6): 1487-501.
1 Xin Hou RZ, Haiming Wei, Rui Sun, Zhigang Tian. NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis. Hepatology, 2009; 49 (3): 940-49.
2 Feng Zhou MNA, Paul L. Beck, Tai Le, Cory M. Hogaboam, Mark G. Swain. CD154-CD40 interactions drive hepatocyte apoptosis in murine fulminant hepatitis. Hepatology, 2005; 42 (2): 372-80.
3 Yang J, Gallagher S, Haines K, Epling-Burnette PK, Bai F, Gower WR, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. Journal of Gastrointestinal Surgery, 2004; 8 (2): 166-74.
4 Hong F, Jaruga B, Kim WH, Radaeva S, El-Assal ON, Tian ZG, Nguyen VA, Gao B. Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS. Journal of Clinical Investigation, 2002; 110 (10): 1503-13.
5 Kim WH, Hong F, Radaeva S, Jaruga B, Fan S, Gao B. STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 2003; 285 (4): G761-68.
6 Tsuji H, Mukaida N, Harada A, Kaneko S, Matsushita E, Nakanuma Y, Tagawa Y, Iwakura Y, Kobayashi K, Matsushima K. Alleviation of Lipopolysaccharide-Induced Acute Liver Injury in Propionibacterium acnes-Primed IFN-γ-Deficient Mice by a Concomitant Reduction of TNF-α, IL-12, and IL-18 Production. Journal of Immunolology, 1999; 162 (2): 1049-55.
7 Nakashima H, Kinoshita M, Nakashima M, Habu Y, Shono S, Uchida T, Shinomiya N, Seki S. Superoxide produced by Kupffer cells is an essential effector in concanavalin A-induced hepatitis in mice. Hepatology, 2008; 48 (6): 1979-88.
8梁萍,薄爱华.苦参碱抗免疫性肝损伤机制的研究.世界华人消化杂志, 1999; 7 (002): 104-08.
9 Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 2006; 44 (6): 1487-501.
10 Lalor PF, Shields P, Grant AJ, Adams DH. Recruitment of lymphocytes to the human liver. Immunology and Cell Biology, 2002; 80 (1): 52-64.
11 Bremer C, Bradford BU, Hunt KJ, Knecht KT, Connor HD, Mason RP, Thurman RG. Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 1994; 267 (4): G630-36.
12 Bilzer M, Jaeschke H, Vollmar AM, Paumgartner G, Gerbes AL. Prevention of Kupffer cell-induced oxidant injury in rat liver by atrial natriuretic peptide. American Journal of Physiology - Gastrointestinal and Liver Physiology, 1999; 276 (5): G1137-44.
13 Titos E, Clària J, PlanagumàA, López-Parra M, González-Périz A, Gaya J, Miquel R, Arroyo V, Rodés J. Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells. Journal of Leukocyte Biology, 2005; 78 (4): 871-78.
14 Tomiyama K, Ikeda A, Ueki S, Nakao A, Stolz DB, Koike Y, Afrazi A, Gandhi C, Tokita D, Geller DA, Murase N. Inhibition of Kupffer cell-mediated earlyproinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats. Hepatology, 2008; 48 (5): 1608-20.
15 Polakos NK, Cornejo JC, Murray DA, Wright KO, Treanor JJ, Crispe IN, Topham DJ, Pierce RH. Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection. American Journal of Pathology, 2006; 168 (4): 1169-78.
16 Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, Pierce RH, Crispe IN. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood, 2007; 110 (12): 4077-85.
17 Terpstra V, van Berkel TJC. Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice. Blood, 2000; 95 (6): 2157-63.
18 van Egmond M, van Garderen E, van Spriel AB, Damen CA, van Amersfoort ES, van Zandbergen G, van Hattum J, Kuiper J, van de Winkel JGJ. FcαRI-positive liver Kupffer cells: Reappraisal of the function of immunoglobulin A in immunity. Nature Medicine, 2000; 6 (6): 680-85.
19 Helmy KY, Katschke KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van lookeren Campagne M. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell, 2006; 124 (5): 915-27.
20 Hildebrand F, Hubbard WJ, Choudhry MA, Frink M, Pape HC, Kunkel SL, Chaudry IH. Kupffer Cells and Their Mediators: The Culprits in Producing Distant Organ Damage after Trauma-Hemorrhage. American Journal of Pathology, 2006; 169 (3): 784-94.
21 Sleyster EC, Knook DL. Relation between localization and function of rat liver Kupffer cells. Laboratory Investigation, 1982; 47 (5): 484-90.
22 Bouwens L, Baekeland M, De Zanger R, Wisse E. Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liver. Hepatology, 1986; 6 (4): 718-22.
23 Bykov I, Ylipaasto P, Eerola L, Lindros KO. Phagocytosis and LPS-stimulated production of cytokines and prostaglandin E2 is different in Kupffer cells isolated from the periportal or perivenous liver region. Scandinavian Journal of Gastroenterology, 2003; 38 (12): 1256-61.
24 Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G. Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood, 1996; 87 (11): 4568-80.
25 Mathison JC, Ulevitch RJ. The clearance, tissue distribution, and cellular localization of intravenously injected lipopolysaccharide in rabbits. The Journal of Immunology, 1979; 123 (5): 2133.
26 van der Laan LJW, D?pp EA, Haworth R, Pikkarainen T, Kangas M, Elomaa O, Dijkstra CD, Gordon S, Tryggvason K, Kraal G. Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo. The Journal of Immunology, 1999; 162 (2): 939-47.
27 Toshiyuki Kitazawa TT, Hideto Kawaratani, Hiroshi Fukui,. Therapeutic approach to regulate innate immune response by Toll-like receptor 4 antagonist E5564 in rats with D-galactosamine-induced acute severe liver injury. Journal of Gastroenterology and Hepatology, 2009; doi:10.1111/j.1440-1746.2008.05770.x.
28 Tu Z, Bozorgzadeh A, Pierce RH, Kurtis J, Crispe IN, Orloff MS. TLR-dependent cross talk between human Kupffer cells and NK cells. Journal of Experimental Medicine, 2008; 205 (1): 233-44.
29 Matthew Giannandrea RHP, Ian Nicholas Crispe. Indirect action of tumor necrosis factor-αin liver injury during the CD8+ T cell response to an adeno-associated virus vector in mice. Hepatology, 2009; doi:10.1002/hep22869.
30 Ahmad N, Chen LC, Gordon MA, Laskin JD, Laskin DL. Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. Journal of Leukocyte Biolology, 2002; 71 (6): 1005-11.
31 Casado M, Callejas NA, Rodrigo J, Zhao X, Dey SK, BoscáL, Martín-Sanz P. Contribution of cyclooxygenase-2 to liver regeneration after partial hepatectomy. FASEB Journal, 2001; 15 (11):2016-8.
32 Souto EO, Miyoshi H, Dubois RN, Gores GJ. Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats. American Journal of Physiology - Gastrointestinal and Liver Physiology, 2001; 280 (5): G805-11.
33 Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil RW, Coito AJ. Cyclooxygenase-2 Deficiency Enhances Th2 Immune Responses and Impairs Neutrophil Recruitment in Hepatic Ischemia/Reperfusion Injury. Journal of Immunology, 2008; 180 (3): 1843-53.
34 Han C, Li G, Lim K, DeFrances MC, Gandhi CR, Wu T. Transgenic Expression of Cyclooxygenase-2 in Hepatocytes Accelerates Endotoxin-Induced Acute Liver Failure. Journal of Immunology, 2008; 181 (11): 8027-35.
35 Perlik V, Li Z, Goorha S, Ballou LR, Blatteis CM. LPS-activated complement, not LPS per se, triggers the early release of PGE2 by Kupffer cells. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 2005; 289 (2): R332-39.
36 Liu H, Wei W, Li X. Celecoxib exacerbates hepatic fibrosis and induces hepatocellular necrosis in rats treated with porcine serum. Prostaglandins & Other Lipid Mediators, 2009; 88 (3-4): 63-7.
37 Ito H, Ando K, Ishikawa T, Saito K, Takemura M, Imawari M, Moriwaki H, Seishima M. Role of TNF-αProduced by Nonantigen-Specific Cells in a Fulminant Hepatitis Mouse Model. Journal of Immunology, 2009; 182 (1): 391-97.
38 Mark JC. Another way for NADPH oxidase to send a signal for liver injury. Gastroenterology, 2005; 129 (6): 2110-13.
39 Samuele DM, Ramón B, David AB. NADPH Oxidase in the Liver: Defensive, Offensive, or Fibrogenic? Gastroenterology, 2006; 131 (1): 272-75.
40 Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase. Hepatology, 2002; 35 (2): 289-98.
41 Yang CY, Kuo TH, Ting LP. Human hepatitis B viral e antigen interacts with cellular interleukin-1 receptor accessory protein and triggers interleukin-1 response. Journal of Biological Chemistry, 2006; 281 (45): 34525-36.
42 Tian Z, Shen X, Feng H, Gao B. IL-1βAttenuates IFN-αβ-induced antiviral activity and STAT1 activation in the liver: involvement of proteasome-dependent pathway. Journal of Immunology, 2000; 165 (7): 3959-65.
43 Bohlinger I, Leist M, Barsig J, Uhlig T, Tiegs G, Wendel A. Interleukin-1 and nitric oxide protect against tumor necrosis factor-induced liver injury through distinct pathways. Hepatology, 1995; 22 (6): 1829-37.
44 Harada H, Wakabayashi G, Takayanagi A, Shimazu M, Matsumoto K, Obara H, Shimizu N, Kitajima M. Transfer of the interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury. Transplantation, 2002; 74 (10): 1434-41.
45 Sun R, Tian ZG, Kulkarni S, Gao B. IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells in CD4+ T Cell and STAT3 dependent manners. Journal of Immunology, 2004; 172 (9): 5648-55.
46 Bourdi M, Eiras DP, Holt MP, Webster MR, Reilly TP, Welch KD, Pohl LR. Role of IL-6 in an IL-10 and IL-4 double knockout mouse model uniquely susceptible to acetaminophen-induced liver injury. Chemical Research Toxicology, 2007; 20 (2): 208-16.
47 Kovalovich K, Li W, DeAngelis R, Greenbaum LE, Ciliberto G, Taub R. Interleukin-6 Protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. Journal of Biological Chemistry, 2001; 276 (28): 26605-13.
48 Galun E, Zeira E, Pappo O, Peters M, Rose-John S. Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury. FASEB Journal, 2000; 14 (13): 1979-87.
49 Herrero C, Hu XY, Li WP, Samuels S, Sharif MN, Kotenko S, Ivashkiv LB. Reprogramming of IL-10 Activity and Signaling by IFN-γ. Journal of Immunology, 2003; 171 (10): 5034-41.
50 Bliss SK, Bliss SP, Beiting DP, Alcaraz A, Appleton JA. IL-10 Regulates Movement of Intestinally Derived CD4+ T Cells to the Liver. Journal of Immunology, 2007; 178 (12): 7974-83.
51 Dinant S, Vetel?inen RL, Florquin S, van Vliet AK, van Gulik TM. IL-10 attenuates hepatic I/R injury and promotes hepatocyte proliferation. Journal of Surgical Research, 2007; 141 (2): 176-82.
52 Tanaka Y, Takahashi A, Watanabe K, Takayama K, Yahata T, Habu S, Nishimura T. A pivotal role of IL-12 in Th1-dependent mouse liver injury. International Immunology, 1996; 8 (4): 569-76.
53 Margenthaler JA, Ku G, Flye MW. Interleukin-12 regulates natural killer cell-dependent Propionibacterium acnes-primed, lipopolysaccharide-induced liver injury. Hepatology Research, 2008; 38 (2): 183-93.
54 Zhu R, Diem S, Araujo LM, Aumeunier A, Denizeau J, Philadelphe E. The pro-Th1 cytokine IL-12 enhances IL-4 production by invariant NKT cells: relevance for T cell-mediated hepatitis. Journal of immunology, 2007; 178 (9): 5435-42.
55 Adachi K, Tsutsui H, Kashiwamura SI, Seki E, Nakano H, Takeuchi O, Takeda K, Okumura K, Kaer LV, Okamura H, Akira S, Nakanishi K. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. Journal of Immunology, 2001; 167 (10): 5928-34.
56 Yajima T, Nishimura H, Saito K, Kuwano H, Yoshikai Y. Overexpression of Interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with mycobacterium bovis Bacillus Calmette-Guérin. Infection and Immunity, 2004; 72 (7): 3855-62.
57 Finotto S, Siebler J, Hausding M, Schipp M, Wirtz S, Klein S, Protschka M, Doganci A, Lehr HA, Trautwein C, Khosravi-Fahr R, Strand D, Lohse A, Galle PR, Blessing M, Neurath MF. Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo. Gut, 2004; 53 (3): 392-400.
58 Faggioni R, Cattley RC, Guo J, Flores S, Brown H, Qi M, Yin SM, Hill D, Scully S, Chen C, Brankow D, Lewis J, Baikalov C, Yamane H, Meng T, Martin F, Hu S, Boone T, Senaldi G. IL-18-binding protein protects against lipopolysaccharide induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice. Journal of Immunology, 2001; 167 (10): 5913-20.
59 Lin W, Zhang J, Hu Z, Qian D. Inhibitory effect of matrine on lipopolysacchride-induced tumor necrosis factor and interleukin-6 production from rat Kupffer cells. Yao Xue Xue Bao, 1997; 32 (2): 93-6.
60 Zhu X, Qiu Y, Shi M, Ding Y. Matrine Protects Sinusoidal Endothelial Cells From Cold Ischemia and Reperfusion Injury in Rat Orthotopic Liver Transplantation. Annals of Clinical Laboratory Science, 2003; 33 (2): 216-25.
61李常青,刘丽丽,莫传伟,黄玲.苦参碱对Con A性肝损伤小鼠IFN释放及肝组织病理改变的影响.世界华人消化杂志, 2005; 13 (005): 640-43.
62赵丽娟,李红,杨世杰.黄芪注射液对d—半乳糖胺所致小鼠急性肝损伤的保护作用.吉林大学学报:医学版, 2003; 29 (3): 280-82.
63侯敬申,潘运龙,覃莉,赵莉.黄芪注射液对刀豆蛋白诱导的小鼠肝脏损伤的保护作用.中华实用中西医杂志, 2005; 18 (20): 1287-89.
64刘印忠,马德禄,高建华,康毅.黄芪注射液对小鼠免疫性肝损伤的保护作用.天津医科大学学报, 2004; 10 (2): 190-91.
65程梦琳,陈金和,吴基良,罗德生,汪素涵.黄芪注射液对大鼠肠缺血再灌注肝损伤NO、SOD的影响.华中医学杂志, 2004; 28 (1): 15-16.
66欧阳雁玲,张明升.黄芪注射液对四氯化碳损伤小鼠肝的保护作用.太原科技, 2002; 3: 26-27.
67汪德清,丁保国,等.黄芪总黄酮对扑热息痛所致小鼠肝损伤防护作用的研究.中国中药杂志, 2001; 26 (7): 483-86.
68杨雁,陈敏珠.黄芪总甙及其单体抗肝损伤作用的机理.中国药理学会通讯, 2001; 18 (4): 10-11.
69路景涛,杨雁,魏伟,陈敏珠.黄芪多部位组合对化学性及免疫性肝损伤小鼠的保护作用.中国中医药信息杂志, 2008; 15 (1): 32-34.
70路景涛,杨雁,陈敏珠.黄芪多糖对细菌脂多糖诱导大鼠腹腔巨噬细胞释放TNF-α, NO及IL-1的影响.安徽医科大学学报, 2004; 39 (002): 139-41.
71路景涛,陈敏珠.复方黄芪提取物对细菌脂多糖诱导大鼠腹腔巨噬细胞分泌TNF-α, NO及IL-1的影响.安徽医药, 2006; 10 (005): 330-31.
72刘协,顾呈华,胡启之,潘玉英.甘草甜素脂质体对小鼠急性酒精性肝损伤的保护作用.中国临床康复, 2004; 8 (36): 8260-61.
73刘东,蒋毅萍,陈志良.甘草甜素与苦参碱联合用药对四氯化碳所致小鼠急、慢性肝损伤的保护作用.中药材, 2007; 30 (5): 581-83.
74王根生,韩哲武.甘草类黄酮对乙醇所致小鼠肝脏脶伤的影响.中国药理学通报, 1993; 9 (4): 271-73.
75王根生,韩哲武.甘草类黄酮对四氯化碳致小鼠急性肝损伤的影响.药学学报, 1993; 28 (8): 572-76.
76尹龙武,吕晓君,杨静,李颖,宛菁.异甘草素对小鼠免疫性肝损伤的保护作用及其机制.中国药理通讯, 2007; 24 (3): 37-37.
77陈冬裕.甘草酸类药物在药物性肝损伤中的应用.海峡药学, 2007; 19 (8): 6-9.
78鲍启德,杨兰兰,王利,崔东来.异甘草酸镁对CCl4诱导小鼠急性肝损伤的保护作用.世界华人消化杂志, 2008; 16 (9): 1004-07.
79吴希美,周汉良,等.小柴胡冲剂对乙酰氨基酚肝损伤的保护作用及机理研究.中药药理与临床, 1997; 13 (6): 8-10.
80邵鸿娥,邵宏元.小柴胡汤加味对小鼠实验性肝损伤的保护作用.山西医药杂志, 1995; 24 (3): 171-72.
81杨错,刘玉兰,张红梅.柴胡乳剂对急性化学性肝损伤的保护作用.沈阳药科大学学报, 2006; 23 (2): 105-08.
82谢斌,张奉学,杨子峰,刘妮.加味小柴胡汤对刀豆蛋白A所致肝损伤的保护作用.中国热带医学, 2006; 6 (4): 572-73.
83李荣萍,任成山,赵晓宴.水飞蓟宾对急性肝损伤中肝细胞胀亡的影响及其机制.中国中西医结合急救杂志, 2006; 13 (4): 202-05.
84王伟,黄爔乐,利红宇,陈一岳.水飞蓟宾对四氯化碳所致肝损伤的治疗与预防作用.广东药学院学报, 2005; 21 (5): 565-67.
85薛洪源,侯艳宁,刘会虑,陈静,曹颖.水飞蓟宾胶囊对异烟肼和利福平肝损害小鼠的保护作用.中成药, 2003; 25 (4): 307-10.
86谭海荣,吴谦,潘竞锵,肖柳英,韩超,林洁茹,郑琳颖,李博萍.水飞蓟宾对抗大鼠酒精性脂肪肝作用及机制.中国临床药理学与治疗学, 2004; 9 (7): 803-06.
87邸琳,刘新宇,常福红,王永生,张群功.芍药甘草汤对小鼠急性肝损伤的保护作用.中药药理与临床, 2007; 23 (6): 4-5.
88詹可顺,王华,魏伟.白芍总苷对小鼠化学性肝损伤的保护作用及机制.安徽医科大学学报, 2006; 41 (6): 664-66.
89王华,魏伟,岳莉,汪倪萍,桂双英,吴丽,孙妩弋,徐叔云.白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用.中国药理学通报, 2004; 20 (8): 875-78.
90路景涛,孙妩弋,刘浩,李响,魏伟.白芍总苷对免疫性肝纤维化大鼠肝组织NF-κB和TGF-β1蛋白表达的影响.中国药理学通报, 2008; 24 (5): 588-92.
91魏伟,刘家骏.白芍总苷对乙型肝炎的治疗作用及其前景.中国药理学通报, 2000; 16 (5): 597-98.
92 Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus calmette-guérin plus lipopolysaccharide: modulation of tumour necrosis factor-αand interleukin-6 mRNA. Clinical and Experimental Pharmacology and Physiology, 2006; 33 (4): 332-39.
93 Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-κB activation through modulation of IκBαand enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomedicine & Pharmacotherapy, 2008; 62 (9): 659-66.
94 Tsai T, Wu S, Liu Y, Wu A, Tsai Y. Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. European Journal of Pharmacology, 2005; 523 (1-3): 16-24.
95 Ye J, Duan H, Yang X, Yan W, Zheng X. Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo. Planta medica, 2001; 67 (8): 766.
96王晓玉,魏伟,唐丽琴,吴虹,杨宇清,陈尹.芍药苷对佐剂性关节炎大鼠腹腔巨噬细胞吞噬功能及其产生细胞因子的影响.安徽医科大学学报, 2007; 42 (2): 189-92.
97陈尹,魏伟,吴虹,张玲玲,陈镜宇.芍药苷对佐剂性关节炎大鼠脾细胞产生抗体和cAMP水平的影响.药学学报, 2007; 42 (11): 1147-51.
98 Chu D, Li C, Wu Q, Shen J. Paeoniflorin prevents hepatic fibrosis of Schistosomiasis japonica by inhibiting TGF-β1 production from macrophages in mice. Frontiers of Medicine in China, 2008; 2 (2): 154-65.
99 Li CR, Zhou Z, Zhu D, Sun YN, Dai JM, Wang SQ. Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. The International Journal of Biochemistry & Cell Biology, 2007; 39 (2): 426-38.
100刘平.中草药的肝损伤问题.中华肝脏病杂志, 2004; 12 (4): 243-43.