红景天苷的抗炎作用及其对炎症信号转导通路的调控
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摘要
红景天苷(salidroside)是传统中药红景天中最重要的有效成份之一,临床上具有抗疲劳,抗氧化,保肝,改善血液循环等多种药理功能。为了提高红景天苷的药用价值,进一步扩大该药在临床上的应用范围,本文对红景天苷的抗炎作用进行了深入研究。首先,利用脂多糖(LPS)刺激小鼠RAW 264.7单核-巨噬细胞建立的体外炎症反应模型,研究红景天苷的体外抗炎活性,并借助细胞内第二信使和炎性信号转导通路平台进一步探索它的分子抗炎作用机制。在此基础上,构建LPS所致小鼠急性肺损伤模型和内毒素血症模型,检测红景天苷对两种动物模型的保护和治疗作用。
LPS是革兰氏阴性菌细胞壁的主要成分,它可以激活巨噬细胞释放多种炎性细胞因子如肿瘤坏死因子α(TNF-α),白细胞介素1β(IL-1β)和白细胞介素6(IL-6)等及炎性介质如一氧化氮(NO)和前列腺素E_2(PGE_2)等,从而形成瀑布效应,导致多种炎症疾病发生,甚至死亡。因此,LPS激活的巨噬细胞已被广泛用于评价各种化学物质的抗炎作用。本论文首先通过建立LPS诱导的小鼠单核-巨噬细胞RAW 264.7的体外炎症模型,研究了不同浓度红景天苷对RAW 264.7细胞的细胞因子TNF-α,IL-1β和IL-6及炎性介质NO和PGE_2分泌的影响。结果显示,红景天苷抑制了TNF-α、IL-6、IL-1β的分泌,这与其mRNA的表达结果一致,并呈现剂量依赖性。另外,红景天苷还能抑制NO、PGE_2的合成。以上数据表明,在体外实验中,红景天苷能够通过调节细胞因子和炎性介质的分泌而发挥抗炎作用。
我们又进一步对LPS诱导细胞因子及炎性介质产生的机制进行了深入研究,细胞第二信使[Ca~(2+)]_i、cAMP/cGMP通路和最常见的两条炎性信号转导通路NF-κB和MAPKs起了关键作用。本实验通过用LPS刺激小鼠的RAW 264.7细胞,测定红景天苷对第二信使[Ca~(2+)]_i、cAMP/cGMP信号通路、NF-κB和MAPKs信号转导通路的影响。结果显示,红景天苷显著抑制了LPS刺激的小鼠RAW 264.7巨噬细胞[Ca~(2+)]_i浓度、NF-κB的活力和ERK、p38 MAPKs蛋白表达,作用呈剂量依赖方式,同时升高了cAMP浓度,但对cGMP无影响。这说明,红景天苷通过调控[Ca~(2+)]_i、cAMP、NF-κB、ERK和p38 MAPKs通路而抑制细胞因子TNF-α、IL-6、IL-1β分泌和炎性介质NO、PGE_2合成。
在体外实验的基础上,我们进一步验证了红景天苷在体内的抗炎作用。通过LPS诱导建立了急性炎症肺损伤模型,来研究预注射红景天苷(120 mg/kg)对急性肺损伤的作用。通过收集肺组织以测定湿干重(W/D)比率、髓过氧化物酶(MPO)活性和观察病理组织学的变化,制备支气管肺泡灌洗液(BALF)以检测蛋白浓度、炎性细胞因子浓度。结果显示预服用红景天苷能显著地降低小鼠肺的干湿重的比率、支气管肺泡灌洗液中蛋白浓度、炎性细胞数量和MPO的活性,抑制了TNF-α、IL-6和IL-1β的分泌,病理切片表明红景天苷明显地减弱LPS导致的肺组织损伤。表明红景天苷对LPS诱导的急性炎症肺损伤具有保护作用。
在LPS诱导的小鼠内毒素血症模型中,我们研究了红景天苷对小鼠内毒血症的预防和治疗作用及对小鼠血清中细胞因子TNF-α,IL-1β,IL-6分泌的影响。实验结果显示,红景天苷通过对小鼠血清炎性细胞因子的抑制作用,提高了内毒血症小鼠的生存率,对小鼠内毒素血症产生较好的预防和治疗作用。
Salidroside is a phenylpropanoid glycoside extracted from Rhodiola rosea and regarded as the most important bioactive component. It has been reported to have various pharmacological properties including anti-aging, anticancer, hepatoprotective, antivirus and antioxidative effects. In this paper, we study the anti-inflammatory activity of salidroside deeply. We built in vitro inflammatory model by LPS-stimulated murine RAW 264.7 macrophages, and further explored anti- inflammatory molecular mechanism of salidrosie by cellular second messenger and inflammatory signal transduction pathway. Meanwhile, we studied the effects of salidroside on LPS-induced murine ALI and endotoxic shock.
LPS-mediated activation of macrophages leads to the production of various cytokines such as tumour necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6) and inflammation mediators such as nitric oxide (NO) and prostaglandin E2 (PGE_2). The production of these cytokines may result in the systemic inflammatory response syndrome (SIRS), severe tissue damage, and septic shock. So lipopolyssacharide (LPS)-activated macrophages have typically been used to evaluate the anti-inflammatory effects of various materials. First, we investigated the effect of different concentrations of salidroside on cytokine TNF-α, IL-1β, IL-6. The result showed that salidroside inhibited TNF-α, IL-6 and IL-1βsecretion level in a dose-dependent manner, consistent with cytokine mRNA expression. Salidroside also inhibited NO and PGE_2 synthesis in LPS-stimulated murine RAW 264.7 macrophages by inhibiting iNOS and COX-2 protein expression, cytosolic free Ca~(2+) ([Ca~(2+)]_i), and increasing cAMP level.
NF-κB and MAPKs are known as important targets for anti-inflammatory molecular mechanism. In order to study anti-infalmmatory molecular mechanism, we further investigated the effect of salidroside on NF-κB and MAPKs signal transduction pathways in LPS-stimulated murine RAW264.7 macrophages. The result showed that salidroside inhibited NF-κB activity, ERK1/2 and p38 protein phosphorylation in a dose-dependent manner. It suggested that salidroside inhibited cytokine TNF-α, IL-1β, IL-6, NO and PGE_2 secretion by regulating both NF-κB and ERK and p38 MAPKs pathways.
We further studied in vivo ant-inflammatory of salidroside. In this study, we established a mouse model of LPS-induced inflammatory lung injury and investigated the effect of salidroside (120 mg/kg) on acute lung injury eight hours after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, histological change. We found that the preadministration of salidroside significantly decreases the W/D ratio of lungs, protein concentrations and the number of total cells, neutrophils, macrophages and leukomonocytes, and histologic analysis indicates that salidroside significantly attenuates tissue injury. Furthermore, salidroside significantly increases LPS-induced lung MPO activity, consistent with its effects on neutrophil infiltration. In addition, salidroside also inhibits the production of TNF-α, L-6, and IL-1β. The results showed that salidroside had a protective effect on LPS-induced inflammatory lung injury in mice.
We investigated the effect of different concentrations of salidroside on preventive and therapeutic effect in LPS-induced endotoxic shock mice, and the effect on cytokine TNF-α, IL-1β, IL-6 production in murine serum. The result showed that salidroside significantly improved murine survival rate and decreased TNF-α, IL-1βand IL-6 level in serum. It suggested that salidroside improved murine survival rate through regulating the level of cytokines.
LPS是革兰氏阴性菌细胞壁的主要成分,它可以激活巨噬细胞释放多种炎性细胞因子如肿瘤坏死因子α(TNF-α),白细胞介素1β(IL-1β)和白细胞介素6(IL-6)等及炎性介质如一氧化氮(NO)和前列腺素E_2(PGE_2)等,从而形成瀑布效应,导致多种炎症疾病发生,甚至死亡。因此,LPS激活的巨噬细胞已被广泛用于评价各种化学物质的抗炎作用。本论文首先通过建立LPS诱导的小鼠单核-巨噬细胞RAW 264.7的体外炎症模型,研究了不同浓度红景天苷对RAW 264.7细胞的细胞因子TNF-α,IL-1β和IL-6及炎性介质NO和PGE_2分泌的影响。结果显示,红景天苷抑制了TNF-α、IL-6、IL-1β的分泌,这与其mRNA的表达结果一致,并呈现剂量依赖性。另外,红景天苷还能抑制NO、PGE_2的合成。以上数据表明,在体外实验中,红景天苷能够通过调节细胞因子和炎性介质的分泌而发挥抗炎作用。
我们又进一步对LPS诱导细胞因子及炎性介质产生的机制进行了深入研究,细胞第二信使[Ca~(2+)]_i、cAMP/cGMP通路和最常见的两条炎性信号转导通路NF-κB和MAPKs起了关键作用。本实验通过用LPS刺激小鼠的RAW 264.7细胞,测定红景天苷对第二信使[Ca~(2+)]_i、cAMP/cGMP信号通路、NF-κB和MAPKs信号转导通路的影响。结果显示,红景天苷显著抑制了LPS刺激的小鼠RAW 264.7巨噬细胞[Ca~(2+)]_i浓度、NF-κB的活力和ERK、p38 MAPKs蛋白表达,作用呈剂量依赖方式,同时升高了cAMP浓度,但对cGMP无影响。这说明,红景天苷通过调控[Ca~(2+)]_i、cAMP、NF-κB、ERK和p38 MAPKs通路而抑制细胞因子TNF-α、IL-6、IL-1β分泌和炎性介质NO、PGE_2合成。
在体外实验的基础上,我们进一步验证了红景天苷在体内的抗炎作用。通过LPS诱导建立了急性炎症肺损伤模型,来研究预注射红景天苷(120 mg/kg)对急性肺损伤的作用。通过收集肺组织以测定湿干重(W/D)比率、髓过氧化物酶(MPO)活性和观察病理组织学的变化,制备支气管肺泡灌洗液(BALF)以检测蛋白浓度、炎性细胞因子浓度。结果显示预服用红景天苷能显著地降低小鼠肺的干湿重的比率、支气管肺泡灌洗液中蛋白浓度、炎性细胞数量和MPO的活性,抑制了TNF-α、IL-6和IL-1β的分泌,病理切片表明红景天苷明显地减弱LPS导致的肺组织损伤。表明红景天苷对LPS诱导的急性炎症肺损伤具有保护作用。
在LPS诱导的小鼠内毒素血症模型中,我们研究了红景天苷对小鼠内毒血症的预防和治疗作用及对小鼠血清中细胞因子TNF-α,IL-1β,IL-6分泌的影响。实验结果显示,红景天苷通过对小鼠血清炎性细胞因子的抑制作用,提高了内毒血症小鼠的生存率,对小鼠内毒素血症产生较好的预防和治疗作用。
Salidroside is a phenylpropanoid glycoside extracted from Rhodiola rosea and regarded as the most important bioactive component. It has been reported to have various pharmacological properties including anti-aging, anticancer, hepatoprotective, antivirus and antioxidative effects. In this paper, we study the anti-inflammatory activity of salidroside deeply. We built in vitro inflammatory model by LPS-stimulated murine RAW 264.7 macrophages, and further explored anti- inflammatory molecular mechanism of salidrosie by cellular second messenger and inflammatory signal transduction pathway. Meanwhile, we studied the effects of salidroside on LPS-induced murine ALI and endotoxic shock.
LPS-mediated activation of macrophages leads to the production of various cytokines such as tumour necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6) and inflammation mediators such as nitric oxide (NO) and prostaglandin E2 (PGE_2). The production of these cytokines may result in the systemic inflammatory response syndrome (SIRS), severe tissue damage, and septic shock. So lipopolyssacharide (LPS)-activated macrophages have typically been used to evaluate the anti-inflammatory effects of various materials. First, we investigated the effect of different concentrations of salidroside on cytokine TNF-α, IL-1β, IL-6. The result showed that salidroside inhibited TNF-α, IL-6 and IL-1βsecretion level in a dose-dependent manner, consistent with cytokine mRNA expression. Salidroside also inhibited NO and PGE_2 synthesis in LPS-stimulated murine RAW 264.7 macrophages by inhibiting iNOS and COX-2 protein expression, cytosolic free Ca~(2+) ([Ca~(2+)]_i), and increasing cAMP level.
NF-κB and MAPKs are known as important targets for anti-inflammatory molecular mechanism. In order to study anti-infalmmatory molecular mechanism, we further investigated the effect of salidroside on NF-κB and MAPKs signal transduction pathways in LPS-stimulated murine RAW264.7 macrophages. The result showed that salidroside inhibited NF-κB activity, ERK1/2 and p38 protein phosphorylation in a dose-dependent manner. It suggested that salidroside inhibited cytokine TNF-α, IL-1β, IL-6, NO and PGE_2 secretion by regulating both NF-κB and ERK and p38 MAPKs pathways.
We further studied in vivo ant-inflammatory of salidroside. In this study, we established a mouse model of LPS-induced inflammatory lung injury and investigated the effect of salidroside (120 mg/kg) on acute lung injury eight hours after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, histological change. We found that the preadministration of salidroside significantly decreases the W/D ratio of lungs, protein concentrations and the number of total cells, neutrophils, macrophages and leukomonocytes, and histologic analysis indicates that salidroside significantly attenuates tissue injury. Furthermore, salidroside significantly increases LPS-induced lung MPO activity, consistent with its effects on neutrophil infiltration. In addition, salidroside also inhibits the production of TNF-α, L-6, and IL-1β. The results showed that salidroside had a protective effect on LPS-induced inflammatory lung injury in mice.
We investigated the effect of different concentrations of salidroside on preventive and therapeutic effect in LPS-induced endotoxic shock mice, and the effect on cytokine TNF-α, IL-1β, IL-6 production in murine serum. The result showed that salidroside significantly improved murine survival rate and decreased TNF-α, IL-1βand IL-6 level in serum. It suggested that salidroside improved murine survival rate through regulating the level of cytokines.
引文
[1] Diks SH, RichelDJ, Peppelenbosch MP. LPS signal transduction:the picture is becoming more complex [J].curr Top Med Chem, 2004, 4(11):1115-1126.
[2] Raetz CRH, Reynolds CM, Trent MS,et al. Lipid A ModificationSystems in Gram-Negative Bacteria [J]. Annu Rev Biochem, 2007, 76: 295?329.
[3] Raetz CRH, Whitfield C. Lipopolysaccharide endotoxins [J]. AnnuRev Biochem, 2002, 71: 635?700.
[4] Galanos C, Lüderitz O, Rietschel ET , et al. Synthetic and naturalEscherichia coli free lipid A express identical endotoxic activities [J].Eur J Biochem, 1985, 148(1): 1?5.
[5] Caroff, Karibian. Structure of bacterial lipopolysaccharides [J].Carbohydr Res, 2003, 338(23): 2431?2447.
[6]罗向东,杨宗城,黎鳌.家兔烧伤早期内脏血管内皮细胞损伤的变化[J].中国创伤杂志, 1998, 14 (3) : 154.
[7]杨一新,李桂源. LPS所介导的信号转导通路研究进展[J].中南大学学报(医学版),2006,31(1):141-145.
[8] TakedaK. Regulationof innate immune responses by Toll-like receptors [J].Jpn J Infect Dis, 2001, 54(6):209-219.
[9]郭萌,李冠民,黄清泉.细菌内毒素研究进展[J].中国实验动物学报, 2009,17(5):397-401.
[10] Hsulc, Parkjm,Zhong k,et al.The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4[J].Nature,2004, 428(6980):341-345.
[11] Cohen J. The immunopathogenesis of sepsis [J]. Nature, 2002, 420(6917): 885-891.
[12] Dinarello CA.Interleukin-1 and interleukin-1 1antagonism [J].Blood, 1991, 77:1627-1652.
[13]马丽梅,郑春兰,马加庆.急性肺损伤与细胞因子相关性的研究进展[J]. Medical Recapitulate, 2009, 19(15): 2009-2012.
[14]杨汉春.动物免疫学(第二版)[M].北京:中国农业大学出版社,2003: 97-98.
[15]陈杖榴.兽医药理学IM}.中国农业出版社, 2005:147.
[16]田成功.糖皮质激素诱导的骨质疏松[J],实用老年医学2000,14(3):124-125.
[17] Tobas, Tapping RI, Gegner JA.Endotoxin interactions with lipopolysacharide- responsive cells [J].ClinInfect Dis,1999,28(3):476-481.
[18] Kitchens RL, Thompson PA, Viriyakosol S, et al. Plasma CD14 decreases monocyte responses to LPS by transferring cell bound LPS to plasma lipoproteins[J]. J Clin Invest, 2001, 108 (4): 485-493.
[19] Wright S D, Ramos RA, Tobias PS , et al . CD14 serves as the cellular receptor for complexes of lipopolysaccharide withlipopolysaccharide binding protein[J] . Science, 1990, 249:1431 -1433.
[20] Janeway CA, Medzhitov R. Innate immune recognition [J]. AnnuRev Immunol, 2002, 20 (5): 197-216.
[21]陈洁,姜宏. TLR4信号通路与炎症反应.医学综述[J], 2009, 15(19):2902-2904.
[22] Shimazu R,Akashi S,Ogata H,et al. MD-2, a molecule that confers LPS responsiveness on Toll-like receptor 4[J].J Exp Med,1999,189(11):1777-1782.
[23] Yang H,Young D W,Gusovsky F,et al.Cellular events mediated by LPS-stimulated Toll-like receptor 4.MD-2 is required foractivation of mitogen-activated protein kinases protein kinases and Elk-1[J].JBiol Chem, 2000, 275(27):20861-20866.
[24]孙佳,夏海鸣.脂多糖相关受体及其介导的信号转导通路[J]. Medical Recapitulate, 2010, 16(3): 3224-327.
[25] Aderem A, Ulevitch R J.Toll-like receptors in the induction of the innate immune response [J].Nature, 2000, 406(6797): 782-787.
[26]李永旺,毛宝龄,钱桂生.内毒素诱导的TLR4-MD2信号转导通路[J].中国药理学报, 2002, 18(2):121-125.
[27] Muzio M,Mantovani A.Toll-like receptors[J].Microbes Infect,2002,2(3):251-255.
[28] Akira S, Takeda K. Toll-like receptor signaling [J]. Nat Rev Immunol, 2004, 4 (7): 499-511.
[29] Sato S, SugiyamaM. TR IF associates with TRAF6 and TBK1, and activates two distinct transcrip tion factors, NF-κB and IRF-3, in the TLR signaling[J]. J Immunol, 2003, 171 (8) : 4304-4310.
[30] Fitzgerald KA, Rowe DC, Barnes BJ, et al. LPS-TLR4 signaling to IRF-3 /7and NF-κB involves the toll adapters TRAM and TRIF [ J ]. J Exp Med, 2003, 198 (7): 1043-1055.
[31] Shishodia S, KoulD, AggarwalBB. Cyclooxygenase (COX) -2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non2small cell lung carcinoma: correlation with suppression of COX-2 synthesis [ J ]. J Imm unol, 2004, 173 (3): 2011-2022.
[32] Bonizzi G, Karin M.The two NF-kappaB activation pathways and their role in innate and adaptive immunity [J].Trends Immunol, 2004, 25(6):280-288.
[33]姜勇. LPS介导细胞激活的信号转导:从CD14到p38MAPK通路的研究.生理科学进展, 1999, 30(1): 29-34.
[34] Diks SH, Richel DJ, Peppelenbosch MP. LPS signal transduction: the picture is becoming more complex [J]. Curr Top Med Chem, 2004, 4(1): 1115-1126.
[35]常用抗炎药物的作用是什么[J].护士进修杂志, 2009, 24(2):192一192.
[36]田成功.糖皮质激素诱导的骨质疏松[J].实用老年医学, 2000,14(3):124-125.
[37]刘利.非幽体抗炎药的不良反应机制及用药安全[J].中国实用医药, 2008, 3(34):201-202.
[38]王文江,姚咏明.中医药抗内毒素血症治疗的研究进展[J].中国中西医结合急救杂志, 2004, 9(11) : 317-320.
[39]詹妮,卢丹,李平亚.中草药的抗炎作用成分及其机制[J].中国医药指南, 2010, 7(8) : 224-226.
[40]鄢顺琴,凤良元,丁荣光.金钱白花蛇抗炎作用的实验研究[J].中药材, 1994, 17 (12) : 29-31.
[41]周辉,张安平,陈敏珠等.白芍总甙对应激大鼠下丘脑-垂体-肾上腺轴和免疫功能的调节[J].中国药理学通报, 1994, 10(6): 429-33.
[42] Ju Dw , Zheng Q Y, Cao X, et al. Esculento side A inh ibits tumornecrosis factor, interleuk in21, and interleuk-6 productioninduced by lipolysaccharide in mice[J]. Pharmacology, 1998, 56(4): 187-192.
[43] Seow WK, FerranteA, Summo A, et al. Comparative effects of tetrandrine and berbamine on production of the inflammato rycytokines interleukin-1 and tumornecrosis factor [J]. Life Sci, 1992, 50 (8): 53-59.
[44]张永健,苏素文,谢彦华,等.雷公多苷的抗炎作用与NO的关系[J].中国药学杂志, 2000, 35 (1) : 20-22.
[45]Wakabayashi I. Inhibitory effects of baicalain and wogonin on LPS-induced nitric oxide production in macrophages [J]. Pharmacol Toxicol, 1999, 84 (6): 288-93.
[46]张又枝等.二苯乙烯苷的抗炎作用及其机制研究[D].武汉:华中科技大学, 2006.
[47]侯艳宁,朱秀媛,程桂芳.黄芩苷的抗炎机理[J].药学学报, 2000, 35(3):161-164.
[48]张骏,翁福海,李会强,等.大黄素对大鼠腹腔巨噬细胞产生TNF、IL-1、IL-6以及细胞内[Ca2+]的影响[J].中草药, 2001, 32(8): 718-721.
[49] Jeong H J, Koo HN, Na HJ, et al . Inhibition of TNF-a and IL-6 production by aucubin through blockade of NF-kappa B activation RBL22H3 mast cells [J], Cytokine, 2002, 18 (5):252-259.
[50]贾莹,颜天华,王秋娟,等.红景天苷对麻醉犬脑循环及大鼠全脑缺血再灌注的影响[J].中国医科大学报, 2008, 39 (1) : 77 - 81.
[51]许光辉.红景天苷镇静催眠作用的药理学研究[D].哈尔滨:黑龙江中医药大学, 2007.
[52]李尔逊,许光辉,李庭利,等.红景天苷对戊巴比妥钠所致小鼠睡眠时间影响的实验研究[J].中医药学报, 2008, 36 (1) : 25 - 26.
[53]王景叶,于榕,姚明辉.红景天苷对缺血再灌注大鼠脑组织损伤的保护作用。中华中医药杂志2010, 03: 456-459. [54杨德森等.红景天苷对脑缺血再灌注大鼠行为及脑梗塞范围的影响。湖北中医学报,2009,11(6):15-17.
[55]刘晓梅等.红景天苷对局灶性脑缺血再灌注大鼠神经可塑性的影响。中国中医药科技2010,1: 27-31.
[56]刘晓梅等.红景天苷对局灶性脑缺血再灌注大鼠神经生长相关蛋白的影响。解剖学研究, 2009, 9: 241-244.
[57]徐琪,祝世功,周家文,等.红景天保护脑缺血再灌注损伤鼠脑细胞的作用及其机制研究[J].中风与神经疾病杂志, 1999, 16 (3) :144 - 146.
[58]宋月英,齐刚,韩景田.红景天对全脑缺血再灌注大鼠海马区及齿状回的保护作用[J] .中国临床康复, 2005, 9 (32): 232 -233.
[59]宋月英,齐刚,韩景田,等.大鼠全脑缺血再灌注损伤后脑内白细胞介素1β变化及红景天苷的影响[J] .中国临床康复, 2006, (11): 30- 32.
[60]宋月英,韩慧文,何瑞波,等.红景天苷对全脑缺血再灌注大鼠皮层nNOS及核酸的影响[J].武警医学院学报, 2007,16(6): 607-609.
[61]宋月英,齐刚,李亚萍,等.红景天苷对全脑缺血再灌注损伤大鼠脑组织肿瘤坏死因子TN F -α表达的影响[ J] .中草药, 2006, 37(6): 907-908.
[62]王景叶,于榕,姚明辉.红景天苷对局灶性脑缺血再灌注大鼠神经可塑性的影响[ J] .中华中医药杂志(原中国医药学报) , 2010, 3(25) : 456 - 459.
[63]贾莹,颜天华,王秋娟,等.红景天苷对麻醉犬脑循环及大鼠全脑缺血再灌注的影响[J].中国药科大学学报, 2008, 39(1): 77～81.
[64] Rosenblum WI. Cytotoxic edema: monitoring itsmagnitude and contribution to brain swelling [J]. J Neuropathol Exp Neuro, 2007, 66(9): 771- 778.
[65] Yang B, Zador Z, Verkmana S. Glial cell aquaporin4 over expression in transgen icmice accelerates cytotoxic brainswelling [J]. J BiolChem, 2008, 283(22): 15280- 15286.
[66]冉建华,孙善全,汪克建,等.红景天苷对大鼠缺血性脑水肿的影响[J].中草药, 2008, 39(8) : 1200- 1204.
[67]郭芳,吕平,李树民.大鼠全脑缺血再灌注损伤神经元Na~+ , K~+ ATP酶亚基的变化[ J].第四军医大学学报, 2006, 27(18): 1675- 1678.
[68]张维烨等.红景天苷对神经干细胞作用的研究[J].黑龙江医药科学,2005, 6: 3-4.
[69]庞鹤等.红景天苷对缺氧缺糖损伤的神经细胞线粒体膜电位和凋亡的影响[J].中医药学刊, 2005, 12: 2144-2146
[70]王华,姚文兵,钱云飞等.红景天苷对N a C N及缺糖诱导PC12细胞凋亡的保护作用[J] .中国药科大学学报, 2007 , 38(3): 273-276.
[71]张文生,朱陵群,牛福玲等.红景天苷对缺氧/缺糖损伤神经细胞的保护作用[J].中国中药杂志, 2004, 29(5): 459-462.
[72]庞鹤,朱陵群,张文生等.红景天苷对缺氧缺糖损伤的神经细胞线粒体膜电位和凋亡的影响[J] .中医药学刊, 2005, 23(12): 2144-2146.
[73]孔福全等,红景天苷对γ射线辐射致DNA损伤的影响。质子辐照致DNA损伤过程中红景天的保护作用[J].中国原子能科学研究院年报, 2010, 7: 179-180.
[74]王振华,张红.红景天苷对X射线辐射损伤防护作用[J].生物物理学报, 2009, 25: 479-480.
[75]张新胜,祝彼得,金沈瑞等.红景天苷对骨髓抑制贫血小鼠骨髓基质金属蛋白酶的影响[J] .生物医学工程学杂志, 2006, 23(6): 1314～1319.
[76]张新胜,祝彼得,黄晓芹等.红景天苷对骨髓抑制贫血小鼠骨髓细胞周期和凋亡相关蛋白表达的影响[J] .四川大学学报(医版), 2005, 36(6): 820-823.
[77]谭洪玲等.红景天苷对心肌细胞缺氧/复氧的保护作用.解放军药学学报2010.03.194-197.
[78] LiangXiao-Qing et al. Effects of Salidroside on Myocardial Ischemia/Reperfusion Injury in Rats [J].Chinese Journal of Natural Medicines 2010, 8(2): 127?131.
[79]张博.红景天苷对H2O2诱导乳鼠心肌细胞凋亡的抑制作用[J].中西医结合心脑血管病杂志, 2008, 6(9):1048-1050.
[80]张金平等.红景天苷通过HIF-1途径对缺氧诱导心肌细胞凋亡的抑制作用[J].第四军医大学学报, 2008, 29 (12):1057-1060.
[81]王海波等.红景天苷及其半乳糖苷类似物体对柯萨奇B3病毒的抑制作用[J].中国医院药学杂志, 2009, 18: 1514-1518.
[82]马莹,颜天华,王秋娟等.红景天苷对犬冠状动脉结扎所致心肌缺血的保护作用[J] .中国药科大学学报, 2007, 3 8( 6 ): 553～557.
[83]马莉等.红景天苷对疲劳小鼠氧化损伤的保护作用[J].中西医结合学报, 2009, 7(3): 237-241.
[84]马莉等红.景天苷对小鼠抗疲劳作用的体内研究[J].武警医学, 2007,11: 818-820.
[85]耿欣等.红景天苷对运动疲劳大鼠红细胞膜的影响[J].中药药理与临床, 2008, 24 (1): 49-51.
[86]于洪伟等.高山红景天苷对外周性疲劳大鼠骨骼肌细胞内ATP、AMP以及Pi含量的影响[J].江西中医药, 2009,11:74-75.
[87] Tan et al. Protective Effects of Salidroside on Endothelial Cell Apoptosis Induced by Cobalt Chloride [J]. Biol pharm bull, 2009, 32:1359-1363.
[88] Hao et al. The effect of several structures for salidroside on its antioxidation activity.Sichuan Daxue Xuebao (Ziran Kexueban)[J], 2009, 46: 697-702.
[89] Cai L., Wang H., Li Q., Qian Y.F., Yao W.B. Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome release and inactivating of caspase cascade [J]. Acta Biochimica Et biophysica Sinica, 2008, 40:796-802.
[90] Yu S., Shen Y.T., Liu J., Ding F. Involvement of ERK1/2 pathway in neuroprotection by salidroside against hydrogen peroxide-induced apoptotic cell death [J]. J mol neurosci, 2010, 40:321-331.
[91] Zhang L., Yu H.X., Sun Y., Lin X.F., Chen B., Tan C., Cao G.X. Wang Z.W. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells [J]. Eur j pharmacol, 2007, 564:18-25.
[92] Huang S.C., Lee F.T., Kuo T.Y., Yang J.H., Chien C.T. Attenuation of Long-Term Rhodiola rosea Supplementation on Exhaustive Swimming-Evoked Oxidative Stress in the Rat[J].Chinese Journal of Physiology, 2009, 52:316-324.
[93]王晓东,刘永忠,刘永刚.红景天苷体外抗肝纤维化的实验研究[J].时珍国医国药, 2004, 15(3): 138-139.
[94]张奕,刘永刚.红景天苷抗大鼠肝星状细胞氧应激脂质过氧化作用的研究[J].中药材, 2005, 28(9): 794～796.
[95]蒋明德,甘新宇,解方为等.红景天苷对乙醛刺激的大鼠肝星状细胞增殖及胶原基因表达的影响[J].药学学报, 2002, 9: 37-40.
[96]王晓东,刘永刚,苏薇薇.红景天苷对小鼠实验性肝损伤的保护作用[J].中药材, 2004, 27(3): 198-199.
[97] Song EK, Kim J H, Kim J S, et al. Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrine2induced cytotoxici2 ty in Hep G2 cells [J]. Phytother Res, 2003, 17 (5): 563 -565.
[98]黄凤霞,丁亚杰,王庆国,等.高山红景天苷对阿霉素肾病大鼠的影响[J].中华肾脏病杂志, 2005, 21(7): 412-415.
[99]王亚平,李伯祥,张雪光.α-平滑肌肌动蛋白在大鼠肾间质损伤时的表达及红景天苷的保护作用[J].中华肾脏病杂志, 2000, 16(2): ll8-122.
[100]李伯祥,王海泉.红景天改善实验性大鼠肾间质纤维化的研究[J].中国中医药信息杂志, 1998,5(11): 21-25.
[101]张淑芹,孙非,刘志屹,等.高山红景天苷抑制白血病细胞生长的实验研究[J].吉林中医药,1999,19(4): 32-36.
[102]王大光,朱文元,马慧军,等.淫羊藿苷等6种中药单体抑制Cloudman S91黑素瘤细胞株黑素合成的研究[J ] .临床皮肤科杂志, 2004 , 33 (4) : 202 - 205.
[103]谢乐斯,刘艳丽,董丹,等.红景天苷对小鼠免疫功能的影响及杀瘤效应[J].大连医科大学学报, 2003, 25 (1) : 22-24.
[104] Lee Y, Lim JW, Kim YM , et al . Induction of alphal-acid gly-coprotein mRNA by cytokines and differentiation in human coloncarcinoma cell [J] . Mol Cells , 2001 , 11 (2) : 164 - 169.
[105]解方为,欧阳学农,蒋明德.红景天甙对人肝癌细胞的诱导分化作用[J] .西南国防医药, 2005 , 15 (6) : 613– 615.
[106]孙立群,王宗贵,朱洪权,等.红景天甙抗二倍体细胞衰老的、实验研究[J] .中国老年学杂志, 2001 , 21 (3) : 225 - 226.
[107]张文生,朱陵群,邓瑞春,等.红景天苷对缺氧P缺糖损伤的SH2SY5Y细胞线粒体膜电位的影响[J] .中国病理理杂志,2004 , 20 (7) : 1218 - 1221.
[108]曹立莉,杜冠华,王敏伟.红景天苷减轻叠氮钠诱导线粒体损伤的作用[J] .药学学报, 2005 , 40 (8) : 700 - 704.
[109] Diaz Lanza AM,AbadMartinezM J, FernandezMatellanoL, et al. L ignan and p henylp ropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity[ J ]. PlantaMed, 2001, 67 (3): 219-223.
[110]周丽君,张振,苏丽,等.高山红景天抗伤害感受作用初探[ J ].大连医科大学报, 2003, 25 (3) : 181-182.
[111]吕世静,毕胜利主编.医学免疫学[M], 2006, 43.
[112] HU C, ZAWISTOWSKI J, LING W, et al. Black rice (Orya sativa L.indica)pigmented fraction suppresses both reactive oxygen species and nitric oxide in both chemical and biological models[J]. J Agric Food Chem, 2003, 51(18): 5271-5277.
[113]茅苏萍,程凯灵,周韵芬.黄茂对单疤病毒性角膜炎患者Th1Th2细胞因子的调节作用[J].中国中西医结合杂志, 2004, 24(2): 121-123.
[114]潘灵辉.细胞因子平衡在炎症反应中作用的研究进展[J].医学综述, 2005, 11(9): 775-777.
[115] Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor-kappa B in pulmonary diseases [J] . Chest , 2000 ,117 (5) :1482-1487.
[116] Park WY, Goodman RB, Steinberg KP, et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome [J] . AmJ Respir Crit Care Med, 2001 ,164 (10) :1896-1903.
[117] Wang HQ, Samrt R C.Overexpression of protein kinase C-alpha in the epidermis of transgenic mice results in striking alterations in phorbol ester induced inflammation and COX-2, MIP-2 and TNF-alpha expression but not tumor promotion [J]. J Cell Sci,1999,112(20):3497-3506.
[118]Posada SI, Terencio MC, Guilléni,et al.Coregulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time-course of murine inflammation [J].Naunyn-Schmiedebergs Arch Pharmacol, 2000,361(1):98-106
[119]彭珊瑛等.银杏内酯B对星形胶质细胞释放NO、IL-6及趋化因子RANTES的影响[J].药学学报, 2010, 45(9): 1103-1108.
[120] Tao ma et al. Contractile effects and intracellular Ca2+ signalling induced by emodin in circular muscle cell of rat colon [J]. World journal of Gastroenterology. 2003, 9(8):1804-1807.
[121]邓家刚等.芒果苷对DHBV感染鸭脾细胞内cAMP,cGMP水平影响的实验研究[J].广西中医药, 2011, 34(1): 57-59.
[122]陈志武,马传庚,徐叔云.钙离子与疼痛及炎症免疫的关系[J].中国药理学通报,1989, 5(2): 65-68.
[123]熊维,金胜威,叶笃筠.钙池操纵的Ca2+通道对炎症的调控[J].生命化学, 2006. 26(1): 35-38.
[124] Wang HY et al.Comparison of intracellular Ca2+ patterns affected by steriodsaponin trilliuo, LC253 and LC239 in cultured cardiomyocytes revealed confocal microscopy [J].中国天然药物, 2003,1(1):41-43.
[125] Edoardo AM.Inflammation and anti-inflammation [M].Firsted.1977:85-98.
[126] Deporter D. et al. Prophosphate induced inflammation:an in vivo study of interrelationship of intracellular cycle AMP and GMP [J]. Agente and Action,1976, 6(4):476.
[127] Bertellia A, et al. Cyclic neuclcotides and activity of anti-inflammatory drugs [J]. Drugs Exp Clin Res,1977, 2(1):177.
[128]姜代勋等.抗炎中药作用机制新靶点研究[J].中兽医医药杂志, 2009, 1: 35-37.
[129] Won Sun Park et al. Cilostazol protects mice against endotoxin shock and attenuates LPS-induced cytokine expression in RAW 264.7 macrophages via MAPK inhibition and NF-κB inactivation: Not involved in cAMP mechanisms [J]. International immunopharmacology, 2010,10(9): 1077-1085.
[130]卢家凯. MAPK与内毒素诱导炎症反应的关系[J].《国外医学》麻醉学与复苏分册, 2000, 21(2): 65-67.
[131] Bhatia M and Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome [J]. J Pathol, 2004, 202: 145–56.
[132] Lee WL and Downey GP. Neutrophil activation and acute lung injury [J]. Curr Opin Crit Care, 2001, 7: 1–7.
[133] Rochelle LG, Fischer BM, Adler KB. Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro [J]. Free Radic Biol Med, 1998, 24: 863-8.
[134] MacCallum NS, Evans TW. Epidemiology of acute lung injury [J]. Curr Opin Crit Care, 2005, 11: 43–9.
[135] Jain R, DalNogare A. Pharmacological therapy for acute respiratory distress syndrome [J]. Mayo Clin Proc, 2006, 81: 205–12.
[136] Iuvone T, Acquisto F, Camuccio R, Rosa MD. Nitric oxide inhibits LPS-induced tumor necrosis factor synthesis in vitro and in vivo [J]. Life Sci, 1996, 59: 207–11.
[137] Rainsford KD., Anti-inflammatory drugs in the 21st century [J]. SubcellBiochem, 42: 3–27.
[138] Brigham KL, Meyrick B. Endotoxin and lung injury [J]. Am Rev Respir Dis, 1986, 133: 913–27.
[139] Worthen GS et al. Neutrophil-mediated pulmonary vascular injury. Synergistic effect of trace amounts of lipopolysaccharide and neutrophil stimuli on vascular permeability and neutrophil sequestration in the lung [J]. Am Rev Respir Dis, 1987, 136: 19–28.
[140] Szarka RJ, Wang N, Smith RH, et al. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation [J]. J Immunol Methods, 1997, 202: 49-57.
[141] Ware LB, Matthay MA. The acute respiratory distress syndrome[J]. N Engl J Med. 2000, 342(18):1334-1349.
[142]高恒,祁克宗,程玉磊.内毒素抑制剂的研究进展[J].上海畜牧兽医通讯, 2006, 6: 10-12.
[143]张寰,吴满平.抗内毒素药物的研究动态[J].中国临床药学杂志, 2003, 12(2): 127-130.
[144] Mesters R,Helterbrand J,Utterback BG, et al.Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J].Crit Care Med, 2000, 28:2209-2216.
[2] Raetz CRH, Reynolds CM, Trent MS,et al. Lipid A ModificationSystems in Gram-Negative Bacteria [J]. Annu Rev Biochem, 2007, 76: 295?329.
[3] Raetz CRH, Whitfield C. Lipopolysaccharide endotoxins [J]. AnnuRev Biochem, 2002, 71: 635?700.
[4] Galanos C, Lüderitz O, Rietschel ET , et al. Synthetic and naturalEscherichia coli free lipid A express identical endotoxic activities [J].Eur J Biochem, 1985, 148(1): 1?5.
[5] Caroff, Karibian. Structure of bacterial lipopolysaccharides [J].Carbohydr Res, 2003, 338(23): 2431?2447.
[6]罗向东,杨宗城,黎鳌.家兔烧伤早期内脏血管内皮细胞损伤的变化[J].中国创伤杂志, 1998, 14 (3) : 154.
[7]杨一新,李桂源. LPS所介导的信号转导通路研究进展[J].中南大学学报(医学版),2006,31(1):141-145.
[8] TakedaK. Regulationof innate immune responses by Toll-like receptors [J].Jpn J Infect Dis, 2001, 54(6):209-219.
[9]郭萌,李冠民,黄清泉.细菌内毒素研究进展[J].中国实验动物学报, 2009,17(5):397-401.
[10] Hsulc, Parkjm,Zhong k,et al.The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4[J].Nature,2004, 428(6980):341-345.
[11] Cohen J. The immunopathogenesis of sepsis [J]. Nature, 2002, 420(6917): 885-891.
[12] Dinarello CA.Interleukin-1 and interleukin-1 1antagonism [J].Blood, 1991, 77:1627-1652.
[13]马丽梅,郑春兰,马加庆.急性肺损伤与细胞因子相关性的研究进展[J]. Medical Recapitulate, 2009, 19(15): 2009-2012.
[14]杨汉春.动物免疫学(第二版)[M].北京:中国农业大学出版社,2003: 97-98.
[15]陈杖榴.兽医药理学IM}.中国农业出版社, 2005:147.
[16]田成功.糖皮质激素诱导的骨质疏松[J],实用老年医学2000,14(3):124-125.
[17] Tobas, Tapping RI, Gegner JA.Endotoxin interactions with lipopolysacharide- responsive cells [J].ClinInfect Dis,1999,28(3):476-481.
[18] Kitchens RL, Thompson PA, Viriyakosol S, et al. Plasma CD14 decreases monocyte responses to LPS by transferring cell bound LPS to plasma lipoproteins[J]. J Clin Invest, 2001, 108 (4): 485-493.
[19] Wright S D, Ramos RA, Tobias PS , et al . CD14 serves as the cellular receptor for complexes of lipopolysaccharide withlipopolysaccharide binding protein[J] . Science, 1990, 249:1431 -1433.
[20] Janeway CA, Medzhitov R. Innate immune recognition [J]. AnnuRev Immunol, 2002, 20 (5): 197-216.
[21]陈洁,姜宏. TLR4信号通路与炎症反应.医学综述[J], 2009, 15(19):2902-2904.
[22] Shimazu R,Akashi S,Ogata H,et al. MD-2, a molecule that confers LPS responsiveness on Toll-like receptor 4[J].J Exp Med,1999,189(11):1777-1782.
[23] Yang H,Young D W,Gusovsky F,et al.Cellular events mediated by LPS-stimulated Toll-like receptor 4.MD-2 is required foractivation of mitogen-activated protein kinases protein kinases and Elk-1[J].JBiol Chem, 2000, 275(27):20861-20866.
[24]孙佳,夏海鸣.脂多糖相关受体及其介导的信号转导通路[J]. Medical Recapitulate, 2010, 16(3): 3224-327.
[25] Aderem A, Ulevitch R J.Toll-like receptors in the induction of the innate immune response [J].Nature, 2000, 406(6797): 782-787.
[26]李永旺,毛宝龄,钱桂生.内毒素诱导的TLR4-MD2信号转导通路[J].中国药理学报, 2002, 18(2):121-125.
[27] Muzio M,Mantovani A.Toll-like receptors[J].Microbes Infect,2002,2(3):251-255.
[28] Akira S, Takeda K. Toll-like receptor signaling [J]. Nat Rev Immunol, 2004, 4 (7): 499-511.
[29] Sato S, SugiyamaM. TR IF associates with TRAF6 and TBK1, and activates two distinct transcrip tion factors, NF-κB and IRF-3, in the TLR signaling[J]. J Immunol, 2003, 171 (8) : 4304-4310.
[30] Fitzgerald KA, Rowe DC, Barnes BJ, et al. LPS-TLR4 signaling to IRF-3 /7and NF-κB involves the toll adapters TRAM and TRIF [ J ]. J Exp Med, 2003, 198 (7): 1043-1055.
[31] Shishodia S, KoulD, AggarwalBB. Cyclooxygenase (COX) -2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non2small cell lung carcinoma: correlation with suppression of COX-2 synthesis [ J ]. J Imm unol, 2004, 173 (3): 2011-2022.
[32] Bonizzi G, Karin M.The two NF-kappaB activation pathways and their role in innate and adaptive immunity [J].Trends Immunol, 2004, 25(6):280-288.
[33]姜勇. LPS介导细胞激活的信号转导:从CD14到p38MAPK通路的研究.生理科学进展, 1999, 30(1): 29-34.
[34] Diks SH, Richel DJ, Peppelenbosch MP. LPS signal transduction: the picture is becoming more complex [J]. Curr Top Med Chem, 2004, 4(1): 1115-1126.
[35]常用抗炎药物的作用是什么[J].护士进修杂志, 2009, 24(2):192一192.
[36]田成功.糖皮质激素诱导的骨质疏松[J].实用老年医学, 2000,14(3):124-125.
[37]刘利.非幽体抗炎药的不良反应机制及用药安全[J].中国实用医药, 2008, 3(34):201-202.
[38]王文江,姚咏明.中医药抗内毒素血症治疗的研究进展[J].中国中西医结合急救杂志, 2004, 9(11) : 317-320.
[39]詹妮,卢丹,李平亚.中草药的抗炎作用成分及其机制[J].中国医药指南, 2010, 7(8) : 224-226.
[40]鄢顺琴,凤良元,丁荣光.金钱白花蛇抗炎作用的实验研究[J].中药材, 1994, 17 (12) : 29-31.
[41]周辉,张安平,陈敏珠等.白芍总甙对应激大鼠下丘脑-垂体-肾上腺轴和免疫功能的调节[J].中国药理学通报, 1994, 10(6): 429-33.
[42] Ju Dw , Zheng Q Y, Cao X, et al. Esculento side A inh ibits tumornecrosis factor, interleuk in21, and interleuk-6 productioninduced by lipolysaccharide in mice[J]. Pharmacology, 1998, 56(4): 187-192.
[43] Seow WK, FerranteA, Summo A, et al. Comparative effects of tetrandrine and berbamine on production of the inflammato rycytokines interleukin-1 and tumornecrosis factor [J]. Life Sci, 1992, 50 (8): 53-59.
[44]张永健,苏素文,谢彦华,等.雷公多苷的抗炎作用与NO的关系[J].中国药学杂志, 2000, 35 (1) : 20-22.
[45]Wakabayashi I. Inhibitory effects of baicalain and wogonin on LPS-induced nitric oxide production in macrophages [J]. Pharmacol Toxicol, 1999, 84 (6): 288-93.
[46]张又枝等.二苯乙烯苷的抗炎作用及其机制研究[D].武汉:华中科技大学, 2006.
[47]侯艳宁,朱秀媛,程桂芳.黄芩苷的抗炎机理[J].药学学报, 2000, 35(3):161-164.
[48]张骏,翁福海,李会强,等.大黄素对大鼠腹腔巨噬细胞产生TNF、IL-1、IL-6以及细胞内[Ca2+]的影响[J].中草药, 2001, 32(8): 718-721.
[49] Jeong H J, Koo HN, Na HJ, et al . Inhibition of TNF-a and IL-6 production by aucubin through blockade of NF-kappa B activation RBL22H3 mast cells [J], Cytokine, 2002, 18 (5):252-259.
[50]贾莹,颜天华,王秋娟,等.红景天苷对麻醉犬脑循环及大鼠全脑缺血再灌注的影响[J].中国医科大学报, 2008, 39 (1) : 77 - 81.
[51]许光辉.红景天苷镇静催眠作用的药理学研究[D].哈尔滨:黑龙江中医药大学, 2007.
[52]李尔逊,许光辉,李庭利,等.红景天苷对戊巴比妥钠所致小鼠睡眠时间影响的实验研究[J].中医药学报, 2008, 36 (1) : 25 - 26.
[53]王景叶,于榕,姚明辉.红景天苷对缺血再灌注大鼠脑组织损伤的保护作用。中华中医药杂志2010, 03: 456-459. [54杨德森等.红景天苷对脑缺血再灌注大鼠行为及脑梗塞范围的影响。湖北中医学报,2009,11(6):15-17.
[55]刘晓梅等.红景天苷对局灶性脑缺血再灌注大鼠神经可塑性的影响。中国中医药科技2010,1: 27-31.
[56]刘晓梅等.红景天苷对局灶性脑缺血再灌注大鼠神经生长相关蛋白的影响。解剖学研究, 2009, 9: 241-244.
[57]徐琪,祝世功,周家文,等.红景天保护脑缺血再灌注损伤鼠脑细胞的作用及其机制研究[J].中风与神经疾病杂志, 1999, 16 (3) :144 - 146.
[58]宋月英,齐刚,韩景田.红景天对全脑缺血再灌注大鼠海马区及齿状回的保护作用[J] .中国临床康复, 2005, 9 (32): 232 -233.
[59]宋月英,齐刚,韩景田,等.大鼠全脑缺血再灌注损伤后脑内白细胞介素1β变化及红景天苷的影响[J] .中国临床康复, 2006, (11): 30- 32.
[60]宋月英,韩慧文,何瑞波,等.红景天苷对全脑缺血再灌注大鼠皮层nNOS及核酸的影响[J].武警医学院学报, 2007,16(6): 607-609.
[61]宋月英,齐刚,李亚萍,等.红景天苷对全脑缺血再灌注损伤大鼠脑组织肿瘤坏死因子TN F -α表达的影响[ J] .中草药, 2006, 37(6): 907-908.
[62]王景叶,于榕,姚明辉.红景天苷对局灶性脑缺血再灌注大鼠神经可塑性的影响[ J] .中华中医药杂志(原中国医药学报) , 2010, 3(25) : 456 - 459.
[63]贾莹,颜天华,王秋娟,等.红景天苷对麻醉犬脑循环及大鼠全脑缺血再灌注的影响[J].中国药科大学学报, 2008, 39(1): 77～81.
[64] Rosenblum WI. Cytotoxic edema: monitoring itsmagnitude and contribution to brain swelling [J]. J Neuropathol Exp Neuro, 2007, 66(9): 771- 778.
[65] Yang B, Zador Z, Verkmana S. Glial cell aquaporin4 over expression in transgen icmice accelerates cytotoxic brainswelling [J]. J BiolChem, 2008, 283(22): 15280- 15286.
[66]冉建华,孙善全,汪克建,等.红景天苷对大鼠缺血性脑水肿的影响[J].中草药, 2008, 39(8) : 1200- 1204.
[67]郭芳,吕平,李树民.大鼠全脑缺血再灌注损伤神经元Na~+ , K~+ ATP酶亚基的变化[ J].第四军医大学学报, 2006, 27(18): 1675- 1678.
[68]张维烨等.红景天苷对神经干细胞作用的研究[J].黑龙江医药科学,2005, 6: 3-4.
[69]庞鹤等.红景天苷对缺氧缺糖损伤的神经细胞线粒体膜电位和凋亡的影响[J].中医药学刊, 2005, 12: 2144-2146
[70]王华,姚文兵,钱云飞等.红景天苷对N a C N及缺糖诱导PC12细胞凋亡的保护作用[J] .中国药科大学学报, 2007 , 38(3): 273-276.
[71]张文生,朱陵群,牛福玲等.红景天苷对缺氧/缺糖损伤神经细胞的保护作用[J].中国中药杂志, 2004, 29(5): 459-462.
[72]庞鹤,朱陵群,张文生等.红景天苷对缺氧缺糖损伤的神经细胞线粒体膜电位和凋亡的影响[J] .中医药学刊, 2005, 23(12): 2144-2146.
[73]孔福全等,红景天苷对γ射线辐射致DNA损伤的影响。质子辐照致DNA损伤过程中红景天的保护作用[J].中国原子能科学研究院年报, 2010, 7: 179-180.
[74]王振华,张红.红景天苷对X射线辐射损伤防护作用[J].生物物理学报, 2009, 25: 479-480.
[75]张新胜,祝彼得,金沈瑞等.红景天苷对骨髓抑制贫血小鼠骨髓基质金属蛋白酶的影响[J] .生物医学工程学杂志, 2006, 23(6): 1314～1319.
[76]张新胜,祝彼得,黄晓芹等.红景天苷对骨髓抑制贫血小鼠骨髓细胞周期和凋亡相关蛋白表达的影响[J] .四川大学学报(医版), 2005, 36(6): 820-823.
[77]谭洪玲等.红景天苷对心肌细胞缺氧/复氧的保护作用.解放军药学学报2010.03.194-197.
[78] LiangXiao-Qing et al. Effects of Salidroside on Myocardial Ischemia/Reperfusion Injury in Rats [J].Chinese Journal of Natural Medicines 2010, 8(2): 127?131.
[79]张博.红景天苷对H2O2诱导乳鼠心肌细胞凋亡的抑制作用[J].中西医结合心脑血管病杂志, 2008, 6(9):1048-1050.
[80]张金平等.红景天苷通过HIF-1途径对缺氧诱导心肌细胞凋亡的抑制作用[J].第四军医大学学报, 2008, 29 (12):1057-1060.
[81]王海波等.红景天苷及其半乳糖苷类似物体对柯萨奇B3病毒的抑制作用[J].中国医院药学杂志, 2009, 18: 1514-1518.
[82]马莹,颜天华,王秋娟等.红景天苷对犬冠状动脉结扎所致心肌缺血的保护作用[J] .中国药科大学学报, 2007, 3 8( 6 ): 553～557.
[83]马莉等.红景天苷对疲劳小鼠氧化损伤的保护作用[J].中西医结合学报, 2009, 7(3): 237-241.
[84]马莉等红.景天苷对小鼠抗疲劳作用的体内研究[J].武警医学, 2007,11: 818-820.
[85]耿欣等.红景天苷对运动疲劳大鼠红细胞膜的影响[J].中药药理与临床, 2008, 24 (1): 49-51.
[86]于洪伟等.高山红景天苷对外周性疲劳大鼠骨骼肌细胞内ATP、AMP以及Pi含量的影响[J].江西中医药, 2009,11:74-75.
[87] Tan et al. Protective Effects of Salidroside on Endothelial Cell Apoptosis Induced by Cobalt Chloride [J]. Biol pharm bull, 2009, 32:1359-1363.
[88] Hao et al. The effect of several structures for salidroside on its antioxidation activity.Sichuan Daxue Xuebao (Ziran Kexueban)[J], 2009, 46: 697-702.
[89] Cai L., Wang H., Li Q., Qian Y.F., Yao W.B. Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome release and inactivating of caspase cascade [J]. Acta Biochimica Et biophysica Sinica, 2008, 40:796-802.
[90] Yu S., Shen Y.T., Liu J., Ding F. Involvement of ERK1/2 pathway in neuroprotection by salidroside against hydrogen peroxide-induced apoptotic cell death [J]. J mol neurosci, 2010, 40:321-331.
[91] Zhang L., Yu H.X., Sun Y., Lin X.F., Chen B., Tan C., Cao G.X. Wang Z.W. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells [J]. Eur j pharmacol, 2007, 564:18-25.
[92] Huang S.C., Lee F.T., Kuo T.Y., Yang J.H., Chien C.T. Attenuation of Long-Term Rhodiola rosea Supplementation on Exhaustive Swimming-Evoked Oxidative Stress in the Rat[J].Chinese Journal of Physiology, 2009, 52:316-324.
[93]王晓东,刘永忠,刘永刚.红景天苷体外抗肝纤维化的实验研究[J].时珍国医国药, 2004, 15(3): 138-139.
[94]张奕,刘永刚.红景天苷抗大鼠肝星状细胞氧应激脂质过氧化作用的研究[J].中药材, 2005, 28(9): 794～796.
[95]蒋明德,甘新宇,解方为等.红景天苷对乙醛刺激的大鼠肝星状细胞增殖及胶原基因表达的影响[J].药学学报, 2002, 9: 37-40.
[96]王晓东,刘永刚,苏薇薇.红景天苷对小鼠实验性肝损伤的保护作用[J].中药材, 2004, 27(3): 198-199.
[97] Song EK, Kim J H, Kim J S, et al. Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrine2induced cytotoxici2 ty in Hep G2 cells [J]. Phytother Res, 2003, 17 (5): 563 -565.
[98]黄凤霞,丁亚杰,王庆国,等.高山红景天苷对阿霉素肾病大鼠的影响[J].中华肾脏病杂志, 2005, 21(7): 412-415.
[99]王亚平,李伯祥,张雪光.α-平滑肌肌动蛋白在大鼠肾间质损伤时的表达及红景天苷的保护作用[J].中华肾脏病杂志, 2000, 16(2): ll8-122.
[100]李伯祥,王海泉.红景天改善实验性大鼠肾间质纤维化的研究[J].中国中医药信息杂志, 1998,5(11): 21-25.
[101]张淑芹,孙非,刘志屹,等.高山红景天苷抑制白血病细胞生长的实验研究[J].吉林中医药,1999,19(4): 32-36.
[102]王大光,朱文元,马慧军,等.淫羊藿苷等6种中药单体抑制Cloudman S91黑素瘤细胞株黑素合成的研究[J ] .临床皮肤科杂志, 2004 , 33 (4) : 202 - 205.
[103]谢乐斯,刘艳丽,董丹,等.红景天苷对小鼠免疫功能的影响及杀瘤效应[J].大连医科大学学报, 2003, 25 (1) : 22-24.
[104] Lee Y, Lim JW, Kim YM , et al . Induction of alphal-acid gly-coprotein mRNA by cytokines and differentiation in human coloncarcinoma cell [J] . Mol Cells , 2001 , 11 (2) : 164 - 169.
[105]解方为,欧阳学农,蒋明德.红景天甙对人肝癌细胞的诱导分化作用[J] .西南国防医药, 2005 , 15 (6) : 613– 615.
[106]孙立群,王宗贵,朱洪权,等.红景天甙抗二倍体细胞衰老的、实验研究[J] .中国老年学杂志, 2001 , 21 (3) : 225 - 226.
[107]张文生,朱陵群,邓瑞春,等.红景天苷对缺氧P缺糖损伤的SH2SY5Y细胞线粒体膜电位的影响[J] .中国病理理杂志,2004 , 20 (7) : 1218 - 1221.
[108]曹立莉,杜冠华,王敏伟.红景天苷减轻叠氮钠诱导线粒体损伤的作用[J] .药学学报, 2005 , 40 (8) : 700 - 704.
[109] Diaz Lanza AM,AbadMartinezM J, FernandezMatellanoL, et al. L ignan and p henylp ropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity[ J ]. PlantaMed, 2001, 67 (3): 219-223.
[110]周丽君,张振,苏丽,等.高山红景天抗伤害感受作用初探[ J ].大连医科大学报, 2003, 25 (3) : 181-182.
[111]吕世静,毕胜利主编.医学免疫学[M], 2006, 43.
[112] HU C, ZAWISTOWSKI J, LING W, et al. Black rice (Orya sativa L.indica)pigmented fraction suppresses both reactive oxygen species and nitric oxide in both chemical and biological models[J]. J Agric Food Chem, 2003, 51(18): 5271-5277.
[113]茅苏萍,程凯灵,周韵芬.黄茂对单疤病毒性角膜炎患者Th1Th2细胞因子的调节作用[J].中国中西医结合杂志, 2004, 24(2): 121-123.
[114]潘灵辉.细胞因子平衡在炎症反应中作用的研究进展[J].医学综述, 2005, 11(9): 775-777.
[115] Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor-kappa B in pulmonary diseases [J] . Chest , 2000 ,117 (5) :1482-1487.
[116] Park WY, Goodman RB, Steinberg KP, et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome [J] . AmJ Respir Crit Care Med, 2001 ,164 (10) :1896-1903.
[117] Wang HQ, Samrt R C.Overexpression of protein kinase C-alpha in the epidermis of transgenic mice results in striking alterations in phorbol ester induced inflammation and COX-2, MIP-2 and TNF-alpha expression but not tumor promotion [J]. J Cell Sci,1999,112(20):3497-3506.
[118]Posada SI, Terencio MC, Guilléni,et al.Coregulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time-course of murine inflammation [J].Naunyn-Schmiedebergs Arch Pharmacol, 2000,361(1):98-106
[119]彭珊瑛等.银杏内酯B对星形胶质细胞释放NO、IL-6及趋化因子RANTES的影响[J].药学学报, 2010, 45(9): 1103-1108.
[120] Tao ma et al. Contractile effects and intracellular Ca2+ signalling induced by emodin in circular muscle cell of rat colon [J]. World journal of Gastroenterology. 2003, 9(8):1804-1807.
[121]邓家刚等.芒果苷对DHBV感染鸭脾细胞内cAMP,cGMP水平影响的实验研究[J].广西中医药, 2011, 34(1): 57-59.
[122]陈志武,马传庚,徐叔云.钙离子与疼痛及炎症免疫的关系[J].中国药理学通报,1989, 5(2): 65-68.
[123]熊维,金胜威,叶笃筠.钙池操纵的Ca2+通道对炎症的调控[J].生命化学, 2006. 26(1): 35-38.
[124] Wang HY et al.Comparison of intracellular Ca2+ patterns affected by steriodsaponin trilliuo, LC253 and LC239 in cultured cardiomyocytes revealed confocal microscopy [J].中国天然药物, 2003,1(1):41-43.
[125] Edoardo AM.Inflammation and anti-inflammation [M].Firsted.1977:85-98.
[126] Deporter D. et al. Prophosphate induced inflammation:an in vivo study of interrelationship of intracellular cycle AMP and GMP [J]. Agente and Action,1976, 6(4):476.
[127] Bertellia A, et al. Cyclic neuclcotides and activity of anti-inflammatory drugs [J]. Drugs Exp Clin Res,1977, 2(1):177.
[128]姜代勋等.抗炎中药作用机制新靶点研究[J].中兽医医药杂志, 2009, 1: 35-37.
[129] Won Sun Park et al. Cilostazol protects mice against endotoxin shock and attenuates LPS-induced cytokine expression in RAW 264.7 macrophages via MAPK inhibition and NF-κB inactivation: Not involved in cAMP mechanisms [J]. International immunopharmacology, 2010,10(9): 1077-1085.
[130]卢家凯. MAPK与内毒素诱导炎症反应的关系[J].《国外医学》麻醉学与复苏分册, 2000, 21(2): 65-67.
[131] Bhatia M and Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome [J]. J Pathol, 2004, 202: 145–56.
[132] Lee WL and Downey GP. Neutrophil activation and acute lung injury [J]. Curr Opin Crit Care, 2001, 7: 1–7.
[133] Rochelle LG, Fischer BM, Adler KB. Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro [J]. Free Radic Biol Med, 1998, 24: 863-8.
[134] MacCallum NS, Evans TW. Epidemiology of acute lung injury [J]. Curr Opin Crit Care, 2005, 11: 43–9.
[135] Jain R, DalNogare A. Pharmacological therapy for acute respiratory distress syndrome [J]. Mayo Clin Proc, 2006, 81: 205–12.
[136] Iuvone T, Acquisto F, Camuccio R, Rosa MD. Nitric oxide inhibits LPS-induced tumor necrosis factor synthesis in vitro and in vivo [J]. Life Sci, 1996, 59: 207–11.
[137] Rainsford KD., Anti-inflammatory drugs in the 21st century [J]. SubcellBiochem, 42: 3–27.
[138] Brigham KL, Meyrick B. Endotoxin and lung injury [J]. Am Rev Respir Dis, 1986, 133: 913–27.
[139] Worthen GS et al. Neutrophil-mediated pulmonary vascular injury. Synergistic effect of trace amounts of lipopolysaccharide and neutrophil stimuli on vascular permeability and neutrophil sequestration in the lung [J]. Am Rev Respir Dis, 1987, 136: 19–28.
[140] Szarka RJ, Wang N, Smith RH, et al. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation [J]. J Immunol Methods, 1997, 202: 49-57.
[141] Ware LB, Matthay MA. The acute respiratory distress syndrome[J]. N Engl J Med. 2000, 342(18):1334-1349.
[142]高恒,祁克宗,程玉磊.内毒素抑制剂的研究进展[J].上海畜牧兽医通讯, 2006, 6: 10-12.
[143]张寰,吴满平.抗内毒素药物的研究动态[J].中国临床药学杂志, 2003, 12(2): 127-130.
[144] Mesters R,Helterbrand J,Utterback BG, et al.Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications[J].Crit Care Med, 2000, 28:2209-2216.