炎症对脂肪细胞功能的影响及其机制探讨
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摘要
目的
肿瘤坏死因子α(TNF-α)作为促炎因子对脂肪细胞功能有多方面的影响，包括促进细胞分化、脂解及脂肪因子分泌等。本文拟研究TNF-α对传代培养的兔皮下脂肪细胞胆固醇流出功能的影响，及可能的作用机制。
方法
来源于兔腹股沟皮下的脂肪细胞以不同浓度的TNF-α(5，10，20 ng／ml)干预24小时。用液体闪烁计数仪测量脂肪细胞对氚标胆固醇的流出率。用逆转录多聚酶链式反应(RT-PCR)检测过氧化物酶体增殖物激活受体γ(PPARγ)、肝X受体α(LXRα)及三磷酸腺苷结合盒转运体A1(ABCA1)的mRNA表达。
结果
1．5或10 ng／ml TNF-α干预脂肪细胞24小时，可使胆固醇流出率增加，且10 ng／ml TNF-α作用最强(7.03±1.17％)，较对照组(3.92±0.46％)明显增高。但20 ng／ml TNF-α反而使胆固醇流出率较10 ng／ml时下降了16.2％(P＜0.05)。
2．5或10 ng／ml TNF-α可上调ABCA1表达，其表达量分别为0.44±0.17和0.91±0.26，与对照组0.20±0.06相比差异有显著性。20 ng／ml TNF-α使ABCA1表达有所下降(0.69±0.13)。与此同时，TNF-α可调节脂肪细胞PPARγ和LXRα表达。在TNF-α≤10 ng／ml时起促进作用，在20 ng／ml时起抑制作用。
3．预先以PPARγ特异性抑制剂GW9662孵育半小时，可抑制10 ng／ml TNF-α对PPARγ(0.88±0.22 vs 1.37±0.25，P＜0.05)和LXRα(0.51±0.14 vs 0.32±0.08，P＜0.05)的诱导作用。
结论
TNF-α影响脂肪细胞胆固醇流出及其ABCA1表达，这种作用与TNF-α对脂肪细胞PPARγ-LXRα的双重调节作用有关。
目的
脂肪细胞肥大伴随一系列功能改变。我们拟研究在氧化低密度脂蛋白(oxLDL)诱导脂肪细胞负荷脂质后，TNF-α对其胆固醇流出和ABCA1表达的影响是否会发生改变。
方法
用50μg／ml oxLDL孵育脂肪细胞24小时制造荷脂模型。再以不同浓度TNF-α(5，10，20 ng／ml)干预24小时，观察胆固醇流出变化及用RT-PCR法检测脂肪细胞PPARγ、LXRα和ABCA1 mRNA表达。
结果
1．OxLDL可使脂肪细胞胆固醇流出增加(7.46±2.34％vs 3.92±0.46％)，PPARγ(1.07±0.26 vs 0.48±0.12)、LXRα(0.83±0.16vs 0.32±0.08)和ABCA1(1.19±0.32 vs 0.20±0.06)表达上升，P均＜0.05。
2．TNF-α抑制荷脂脂肪细胞胆固醇流出，10 ng／ml时作用最强(6.02±0.31％vs3.92±0.46％)，在20 ng／ml时脂肪细胞胆固醇流出率略有回升(6.12±0.53)，差异有显著性。
3．从5 ng／ml到20 ng／ml TNF-α，PPARγ表达量分别为0.93±0.21，0.77±0.15，0.60±0.16与oxLDL对照组1.07±0.26相比表达降低。LXRα表达量为0.72±0.19，0.61±0.17，0.49±0.09与oxLDL对照组0.83±0.16相比也有降低。TNF-α呈浓度依赖性抑制脂肪细胞PPARγ和LXRα表达。5 ng／ml和10 ng／ml TNF-α分别使脂肪细胞ABCA1表达下降了14.4％和34.5％，20ng／ml TNF-α使ABCA1表达有所回升。
结论
在oxLDL诱导荷脂的脂肪细胞中，TNF-α对PPARγ和LXRα表达主要表现为抑制作用，并在一定程度上影响到ABCA1表达及脂肪细胞胆固醇流出。
目的
姜黄素是一类中药提取物，已证实其具有抗炎、抗氧化及改善血脂异常等作用。本研究观察了姜黄素对脂肪细胞抗炎脂肪因子脂联素表达和分泌的影响，初步评价姜黄素对脂肪细胞功能的影响。
方法
新西兰大白兔腹股沟皮下脂肪细胞以不同浓度姜黄素(5，10，20μg／ml)孵育24小时，用ELISA试剂盒检测细胞培养上清液脂联素水平，并用RT-PCR方法检测脂联素及其上游因子PPARγ的表达。
结果
5μg／ml至20μg／ml姜黄素分别使兔皮下脂肪细胞脂联素分泌水平较对照组(3.13±0.21μmol／l)增加(3.93±0.26，4.49±0.34，5.21±0.39μmol／l)。脂联素mRNA表达也较对照组(0.40±0.10)增加(0.55±0.09，0.66±0.11，0.80±0.13)。姜黄素促进PPARγ表达的作用与脂联素表达的改变一致，并在20μg／ml时达到最大(1.01±0.15vs 0.48±0.12，P＜0.05)。
结论
姜黄素可促进兔皮下脂肪细胞脂联素的表达和分泌，这种作用与其上调脂肪细胞PPARγ表达有关。
Objective
The pro-inflammatory cytokine TNF-αhas multiple effects on adipocyte function, including differentiation, lipolyis and the production of adipokines. In this paper, we have evaluated the effects of TNF-αon cholesterol efflux in passaged rabbit subcutaneous adipocyte, which had been elucidated in macrophages, and the possible mechanism involved.
Methods
Passaged rabbit inguina subcutaneous adipocytes were incubated with 5, 10, 20 ng/ml different doses of TNF-αfor 24 hrs. The cholesterol effiux onto apolipoprotein AⅠ(apoAⅠ) was assessed, and the related peroxisome proliferator activated receptorγ(PPARγ), liver X receptorα(LXRα) and ATP-binding cassette transporter A1 (ABCA1) mRNA expression in adipocytes were quantitated by reverse transcription polymerase chain reaction (RT-PCR).
Results
1. Treatment of normal passaged adipocytes with TNF-α(5 or 10 ng/ml) for 24 hrs increased the level of cholesterol effiux onto apoAⅠ, and the effct of 10 ng/ml TNF-αwas significant (7.03±1.17% vs 3.92± 0.46%, P＜0.01). In contrast, 20 ng/ml TNF-αdecreased cholesterol effulux by 16.2% compared with 10 ng/ml TNF-α( P<0.05).
2. The expression of ABCA1 was elevated under treatment of 5 or 10 ng/ml TNF-α(0.444±0.17 vs 0.204±0.06, 0.914±0.26 vs 0.20±0.06, respectively, P＜0.05), and inhibited by 20 ng/ml TNF-α(0.694±0.13). In consistence with the change of ABCA1, the PPARγand LXRαmRNA were significantly induced by 10 ng/ml TNF-α(1.36±0.25 vs 0.48±0.12, 0.844±0.18 vs 0.324±0.08) and downregulated by higher TNF-α.
3. After pre-treated by PPARγspecial inbhibitor GW9662 for half an hour, the introduction of PPARγby 10 ng/ml TNF-αwas partially prevented, subsequent to the downregulation of LXRαand ABCA1.
Conclusion
TNF-αaffects cholesterol effiux and ABCA1 expression of adipocytes, and the pathway of PPARγ-LXRα-ABCA1 is probably involved.
Objective
Obesity is caused by increased adipose mass, which is characterized with enlarged adipocytes. The energy homeostasis management and endocrinal function of enlarged fat cell under certain state, e.g lipid-laden, will be different with that of normal cells. Here we have investigated the effect of pro-inflammatory cytokine TNF-αon cholesterol effulux in the cholesterol laden adipocytes, which was induced by oxidized low density lipoprotein (oxLDL), and the possible mediators in its action.
Methods
Adipocyte isolated from the New Zealand White Rabbit inguina subcutaneous adipose were incubated with 50/zg/ml oxLDL for 24 hrs, then were treated with different doses of TNF-α(5, 10, 20 ng/ml) for another 24 hrs. The cholesterol efflux onto apoAⅠwas assessed. The related gene of PPARγ, LXRαand ABCA1 expression in adipocytes were evaluated by RT-PCR.
Results
1. Cholesterol efflux was induced by uptake of oxLDL in adipocyte (7.46±2.34% vs 3.92±0.46%, P＜0.05). TNF-αsignificantly inhibited the effects of oxLDL under 5 or 10 ng/ml (6.02±0.31%, 4.56±1.62%). 20 ng/ml TNF-αreversed the downregulation to some extent (6.12±0.53%).
2. ABCA1 mRNA was increased in lipid-laden adipocyte induced by oxLDL (1.19±0.32 vs 0.20±0.06), and decreased under addition of 5 ng/ml TNF-α(1.02±0.29) or 10 ng/ml TNF-α(0.78±0.24). In contast, 20 ng/ml TNF-αprevented the downregulation (0.98±0.17).
3. The induction of PPARγand LXRαmRNA in lipid-laden adipocyte were decreased by TNF-αin a dose dependent pattern. From the low to the high dose of TNF-α, PPARγexpression was 0.93±0.21, 0.77±0.15, 0.60±0.16 compared with oxLDL control group 1.07±0.26. LXRαexpression was 0.72±0.19, 0.61±0.17, 0.49±0.09 compared with oxLDL control group 0.83±0.16.
Conclusion
TNF-αdownregulated the augmentation of PPARγand LXRαresulted from lipid burden in rabbit subcutaneous adipocyte induced by oxLDL, and subsequently influenced the expression of ABCA1 and cholesterol effiux.
Objective
To investigate the potential benefits of curcumin, an extract from traditional medical plants, on adipocyte function.
Methods
Rabbit subcutaneous adipocytes were treated with 5, 10, 20μg/ml curcumin for 24 hrs. One of the major adipokines, adiponectin secretion in supernatant was examined by special ELISA kit. The expression of adiponectin and PPARγ, its upstream regulator, were quantitated by RT-PCR.
Results
1. Curcumin increased the adiponectin secretion examined in supernatant in a dose dependent pattern. From 5μg/ml to 20μg/ml, the secretion of adiponectin were 3.93±0.26, 4.49±0.34, 5.21±0.39 vs 3.13±0.21μmol/1 (control group).
2. Curcumin induced the expression of PPARγin cultured adipocyte, and reached its peak value on 20μg/ml (1.01±0.15 vs 0.48±0.12). The adiponectin mRNA was also increased under treatment of all the doses of curcumin (0.55±0.09, 0.66±0.11, 0.80±0.13 vs 0.40±0.10).
Conclusion
Curcumin is able to induce the expression and secretion of adiponectin in adipocyte, which related to its upregulation of expression of PPARγ.
肿瘤坏死因子α(TNF-α)作为促炎因子对脂肪细胞功能有多方面的影响，包括促进细胞分化、脂解及脂肪因子分泌等。本文拟研究TNF-α对传代培养的兔皮下脂肪细胞胆固醇流出功能的影响，及可能的作用机制。
方法
来源于兔腹股沟皮下的脂肪细胞以不同浓度的TNF-α(5，10，20 ng／ml)干预24小时。用液体闪烁计数仪测量脂肪细胞对氚标胆固醇的流出率。用逆转录多聚酶链式反应(RT-PCR)检测过氧化物酶体增殖物激活受体γ(PPARγ)、肝X受体α(LXRα)及三磷酸腺苷结合盒转运体A1(ABCA1)的mRNA表达。
结果
1．5或10 ng／ml TNF-α干预脂肪细胞24小时，可使胆固醇流出率增加，且10 ng／ml TNF-α作用最强(7.03±1.17％)，较对照组(3.92±0.46％)明显增高。但20 ng／ml TNF-α反而使胆固醇流出率较10 ng／ml时下降了16.2％(P＜0.05)。
2．5或10 ng／ml TNF-α可上调ABCA1表达，其表达量分别为0.44±0.17和0.91±0.26，与对照组0.20±0.06相比差异有显著性。20 ng／ml TNF-α使ABCA1表达有所下降(0.69±0.13)。与此同时，TNF-α可调节脂肪细胞PPARγ和LXRα表达。在TNF-α≤10 ng／ml时起促进作用，在20 ng／ml时起抑制作用。
3．预先以PPARγ特异性抑制剂GW9662孵育半小时，可抑制10 ng／ml TNF-α对PPARγ(0.88±0.22 vs 1.37±0.25，P＜0.05)和LXRα(0.51±0.14 vs 0.32±0.08，P＜0.05)的诱导作用。
结论
TNF-α影响脂肪细胞胆固醇流出及其ABCA1表达，这种作用与TNF-α对脂肪细胞PPARγ-LXRα的双重调节作用有关。
目的
脂肪细胞肥大伴随一系列功能改变。我们拟研究在氧化低密度脂蛋白(oxLDL)诱导脂肪细胞负荷脂质后，TNF-α对其胆固醇流出和ABCA1表达的影响是否会发生改变。
方法
用50μg／ml oxLDL孵育脂肪细胞24小时制造荷脂模型。再以不同浓度TNF-α(5，10，20 ng／ml)干预24小时，观察胆固醇流出变化及用RT-PCR法检测脂肪细胞PPARγ、LXRα和ABCA1 mRNA表达。
结果
1．OxLDL可使脂肪细胞胆固醇流出增加(7.46±2.34％vs 3.92±0.46％)，PPARγ(1.07±0.26 vs 0.48±0.12)、LXRα(0.83±0.16vs 0.32±0.08)和ABCA1(1.19±0.32 vs 0.20±0.06)表达上升，P均＜0.05。
2．TNF-α抑制荷脂脂肪细胞胆固醇流出，10 ng／ml时作用最强(6.02±0.31％vs3.92±0.46％)，在20 ng／ml时脂肪细胞胆固醇流出率略有回升(6.12±0.53)，差异有显著性。
3．从5 ng／ml到20 ng／ml TNF-α，PPARγ表达量分别为0.93±0.21，0.77±0.15，0.60±0.16与oxLDL对照组1.07±0.26相比表达降低。LXRα表达量为0.72±0.19，0.61±0.17，0.49±0.09与oxLDL对照组0.83±0.16相比也有降低。TNF-α呈浓度依赖性抑制脂肪细胞PPARγ和LXRα表达。5 ng／ml和10 ng／ml TNF-α分别使脂肪细胞ABCA1表达下降了14.4％和34.5％，20ng／ml TNF-α使ABCA1表达有所回升。
结论
在oxLDL诱导荷脂的脂肪细胞中，TNF-α对PPARγ和LXRα表达主要表现为抑制作用，并在一定程度上影响到ABCA1表达及脂肪细胞胆固醇流出。
目的
姜黄素是一类中药提取物，已证实其具有抗炎、抗氧化及改善血脂异常等作用。本研究观察了姜黄素对脂肪细胞抗炎脂肪因子脂联素表达和分泌的影响，初步评价姜黄素对脂肪细胞功能的影响。
方法
新西兰大白兔腹股沟皮下脂肪细胞以不同浓度姜黄素(5，10，20μg／ml)孵育24小时，用ELISA试剂盒检测细胞培养上清液脂联素水平，并用RT-PCR方法检测脂联素及其上游因子PPARγ的表达。
结果
5μg／ml至20μg／ml姜黄素分别使兔皮下脂肪细胞脂联素分泌水平较对照组(3.13±0.21μmol／l)增加(3.93±0.26，4.49±0.34，5.21±0.39μmol／l)。脂联素mRNA表达也较对照组(0.40±0.10)增加(0.55±0.09，0.66±0.11，0.80±0.13)。姜黄素促进PPARγ表达的作用与脂联素表达的改变一致，并在20μg／ml时达到最大(1.01±0.15vs 0.48±0.12，P＜0.05)。
结论
姜黄素可促进兔皮下脂肪细胞脂联素的表达和分泌，这种作用与其上调脂肪细胞PPARγ表达有关。
Objective
The pro-inflammatory cytokine TNF-αhas multiple effects on adipocyte function, including differentiation, lipolyis and the production of adipokines. In this paper, we have evaluated the effects of TNF-αon cholesterol efflux in passaged rabbit subcutaneous adipocyte, which had been elucidated in macrophages, and the possible mechanism involved.
Methods
Passaged rabbit inguina subcutaneous adipocytes were incubated with 5, 10, 20 ng/ml different doses of TNF-αfor 24 hrs. The cholesterol effiux onto apolipoprotein AⅠ(apoAⅠ) was assessed, and the related peroxisome proliferator activated receptorγ(PPARγ), liver X receptorα(LXRα) and ATP-binding cassette transporter A1 (ABCA1) mRNA expression in adipocytes were quantitated by reverse transcription polymerase chain reaction (RT-PCR).
Results
1. Treatment of normal passaged adipocytes with TNF-α(5 or 10 ng/ml) for 24 hrs increased the level of cholesterol effiux onto apoAⅠ, and the effct of 10 ng/ml TNF-αwas significant (7.03±1.17% vs 3.92± 0.46%, P＜0.01). In contrast, 20 ng/ml TNF-αdecreased cholesterol effulux by 16.2% compared with 10 ng/ml TNF-α( P<0.05).
2. The expression of ABCA1 was elevated under treatment of 5 or 10 ng/ml TNF-α(0.444±0.17 vs 0.204±0.06, 0.914±0.26 vs 0.20±0.06, respectively, P＜0.05), and inhibited by 20 ng/ml TNF-α(0.694±0.13). In consistence with the change of ABCA1, the PPARγand LXRαmRNA were significantly induced by 10 ng/ml TNF-α(1.36±0.25 vs 0.48±0.12, 0.844±0.18 vs 0.324±0.08) and downregulated by higher TNF-α.
3. After pre-treated by PPARγspecial inbhibitor GW9662 for half an hour, the introduction of PPARγby 10 ng/ml TNF-αwas partially prevented, subsequent to the downregulation of LXRαand ABCA1.
Conclusion
TNF-αaffects cholesterol effiux and ABCA1 expression of adipocytes, and the pathway of PPARγ-LXRα-ABCA1 is probably involved.
Objective
Obesity is caused by increased adipose mass, which is characterized with enlarged adipocytes. The energy homeostasis management and endocrinal function of enlarged fat cell under certain state, e.g lipid-laden, will be different with that of normal cells. Here we have investigated the effect of pro-inflammatory cytokine TNF-αon cholesterol effulux in the cholesterol laden adipocytes, which was induced by oxidized low density lipoprotein (oxLDL), and the possible mediators in its action.
Methods
Adipocyte isolated from the New Zealand White Rabbit inguina subcutaneous adipose were incubated with 50/zg/ml oxLDL for 24 hrs, then were treated with different doses of TNF-α(5, 10, 20 ng/ml) for another 24 hrs. The cholesterol efflux onto apoAⅠwas assessed. The related gene of PPARγ, LXRαand ABCA1 expression in adipocytes were evaluated by RT-PCR.
Results
1. Cholesterol efflux was induced by uptake of oxLDL in adipocyte (7.46±2.34% vs 3.92±0.46%, P＜0.05). TNF-αsignificantly inhibited the effects of oxLDL under 5 or 10 ng/ml (6.02±0.31%, 4.56±1.62%). 20 ng/ml TNF-αreversed the downregulation to some extent (6.12±0.53%).
2. ABCA1 mRNA was increased in lipid-laden adipocyte induced by oxLDL (1.19±0.32 vs 0.20±0.06), and decreased under addition of 5 ng/ml TNF-α(1.02±0.29) or 10 ng/ml TNF-α(0.78±0.24). In contast, 20 ng/ml TNF-αprevented the downregulation (0.98±0.17).
3. The induction of PPARγand LXRαmRNA in lipid-laden adipocyte were decreased by TNF-αin a dose dependent pattern. From the low to the high dose of TNF-α, PPARγexpression was 0.93±0.21, 0.77±0.15, 0.60±0.16 compared with oxLDL control group 1.07±0.26. LXRαexpression was 0.72±0.19, 0.61±0.17, 0.49±0.09 compared with oxLDL control group 0.83±0.16.
Conclusion
TNF-αdownregulated the augmentation of PPARγand LXRαresulted from lipid burden in rabbit subcutaneous adipocyte induced by oxLDL, and subsequently influenced the expression of ABCA1 and cholesterol effiux.
Objective
To investigate the potential benefits of curcumin, an extract from traditional medical plants, on adipocyte function.
Methods
Rabbit subcutaneous adipocytes were treated with 5, 10, 20μg/ml curcumin for 24 hrs. One of the major adipokines, adiponectin secretion in supernatant was examined by special ELISA kit. The expression of adiponectin and PPARγ, its upstream regulator, were quantitated by RT-PCR.
Results
1. Curcumin increased the adiponectin secretion examined in supernatant in a dose dependent pattern. From 5μg/ml to 20μg/ml, the secretion of adiponectin were 3.93±0.26, 4.49±0.34, 5.21±0.39 vs 3.13±0.21μmol/1 (control group).
2. Curcumin induced the expression of PPARγin cultured adipocyte, and reached its peak value on 20μg/ml (1.01±0.15 vs 0.48±0.12). The adiponectin mRNA was also increased under treatment of all the doses of curcumin (0.55±0.09, 0.66±0.11, 0.80±0.13 vs 0.40±0.10).
Conclusion
Curcumin is able to induce the expression and secretion of adiponectin in adipocyte, which related to its upregulation of expression of PPARγ.
引文
[1]Guzik T J, Mangalat D, Korbut R. Adipocytokines - novel link between inflammation and vascular function?[J]. J Physiol Pharmacol, 2006, 57(4): 505— 528.
[2]Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion.[J]. J Clin Endocrinol Metab, 2006,:
[3]Murdolo G, Smith U. The dysregulated adipose tissue: A connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis.[J]. Nutr Metab Cardiovasc Dis, 2006,16S1: 35—38.
[4]Le L S, Robichon C, Le X, et al. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells[J]. J.Lipid Res., 2003,44:1499-1507.
[5]Van G L, Mertens I L, De B C. Mechanisms linking obesity with cardiovascular disease.[J]. Nature, 2006,444(7121): 875~880.
[6]Berg A H, Scherer P E. Adipose tissue, inflammation, and cardiovascular disease.[J]. Circ Res, 2005, 96(9): 939-949.
[7]Ruan H, Lodish H F. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha.[J]. Cytokine Growth Factor Rev, 2003,14(5): 447-455.
[8]Uysal K T, Wiesbrock S M, Marino M W, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function.[J]. Nature, 1997, 389(6651): 610-614.
[9]Bouloumie A, Curat C A, Sengenes C, et al. Role of macrophage tissue infiltration in metabolic diseases.[J]. Curr Opin Clin Nutr Metab Care, 2005, 8(4): 347-354.
[10]Xu H, Barnes G T, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.[J]. J Clin Invest, 2003,112(12): 1821—1830.
[11]Weisberg S P, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue.[J]. J Clin Invest, 2003, 112(12): 1796-1808.
[12]Ruan H, Hacohen N, Golub T R, et al. Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.[J]. Diabetes, 2002, 51(5): 1319～1336.
[13] Lee J Y, Plakidas A, Lee W H, et al. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.[J]. J Lipid Res, 2003, 44(3): 479～486.
[14] Suganami T, Nishida J, Ogawa Y. A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes Role of Free Fatty Acids and Tumor Necrosis Factor α[J]. Arterioscler Thromb Vasc Biol., 2005, 25: 0～0.
[15] Wang B, Jenkins J R, Trayhurn P. Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha.[J]. Am J Physiol Endocrinol Metab, 2005, 288(4): 731～740.
[16] Kim K Y, Kim J K, Jeon J H, et al. c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes.[J]. Biochem Biophys Res Commun, 2005, 327(2): 460～467.
[17] 杨再刚，张木勋，许莉军，et al. Effect of Tumor Necrosis Factor-α on Resistin Expression in 3T3-L1 Adipocytes and Its Mechanism[J]．华中科技大学学报(医学英德文版)，2005，25(02)：121～130．
[18] Shojima N, Sakoda H, Ogihara T, et al. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells.[J]. Diabetes, 2002, 51(6): 1737～1744.
[19] Wang B, Trayhurn P. Acute and prolonged effects of TNF-alpha on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture. [J]. Pflugers Arch, 2006, 452(4): 418～427.
[20] Kirchgessner T G, Uysal K T, Wiesbrock S M, et al. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes.[J]. J Clin Invest, 1997, 100(11): 2777～2782.
[21] Xu G R, Li H, Pan L X, et al. FXR-mediated down-regulation of CYP7A1 dominates LXR in long-term cholesterol-fed NZW rabbits[J]. J. Lipid Res, 2003, 44: 1956—1962.
[22] Liver X receptor-α mediates cholesterol efflux in glomerular mesangial cells[J]. Am J Physiol Renal Physiol, 2004, :
[23] Neufeld E B, Remaley A T, Demosky S J, et al. Cellular localization and trafficking of the human ABCA1 transporter.[J]. J Biol Chem, 2001, 276(29): 27584～27590.
[24] 许竹梅，赵水平．ATP结合盒转运子调节细胞内胆固醇流出及对动脉粥样硬化的影响[J]．中国动脉硬化杂志，2002，10(5)：449．
[25] Ruan H, Miles P D, Ladd C M, et al. Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance.[J]. Diabetes, 2002, 51(11): 3176～3188.
[26] Rieusset J, Andreelli F, Auboeuf D, et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes.[J]. Diabetes, 1999, 48(4): 699～705.
[27] Nagy L, Tontonoz P, Alvarez J G, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma.[J]. Cell, 1998, 93(2): 229～240.
[28] 王浩，杨晔．PPARγ PPARγ配体TZDs与高血压[J]．心肺血管病杂志，2005，(04)：245～246249.
[29] Chambrier C, Bastard J P, Rieusset J, et al. Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma.[J]. Obes Res, 2002, 10(6): 518～525.
[30] ChinettiG,GriglioS,AntonucciM,etal.Activationof proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages.[J]. J Biol Chem, 1998, 273(40): 25573～25580.
[31] 刘东，曾邦雄，张世范．过氧化物酶体增殖物激活受体γ与脓毒症的关系[J]．中国危重病急救医学，2005，(04)：244～246．
[32] Davies J D, Carpenter K L, Challis I R, et al. Adipocytic differentiation and liver x receptor pathways regulate the accumulation of triacylglycerols in human vascular smooth muscle cells.[J]. J Biol Chem, 2005, 280(5): 3911～3919.
[33] Seo J B, Moon H M, Kim W S, et alo Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferator-activated receptor gamma expression. [J]. Mol Cell Biol, 2004, 24(8): 3430～3444.
[34] Gerbod-Giannone M C, Li Y, Holleboom A, et al. TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells.[J]. Proc Natl Acad Sci U S A, 2006, 103(9): 3112～3117.
[35] Zhang B, Berger J, Hu E, et al. Negative regulation of peroxisome proliferator-activatedreceptor-gammageneexpressioncontributestothe antiadipogenic effects of tumor necrosis factor-alpha.[J]. Mol Endocrinol, 1996, 10(11): 1457～1466.
[36] Bastard J P, Hainque B, Dusserre E, et al. Peroxisome proliferator activated receptor-gamma, leptin and tumor necrosis factor-alpha mRNA expression during very low calorie diet in subcutaneous adipose tissue in obese women.[J]. Diabetes Metab Res Rev, 1999, 15(2): 92～98.
[37] Wang X, Sato R, Brown M S, et al. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.[J]. Cell, 1994, 77(1): 53～62.
[38] Rosen E D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogenesis.[J]. Genes Dev, 2000, 14(11): 1293～1307.
[39] Sewter C, Berger D, Considine R V, et al. Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha.[J]. Diabetes, 2002, 51(4): 1035～1041.
[40] Prins J B, Niesler C U, Winterford C M, et al. Tumor necrosis factor-alpha induces apoptosis of human adipose cells.[J]. Diabetes, 1997, 46(12): 1939～1944.
[41] 吴智鸿，赵水平．脂肪细胞胆固醇代谢及其病理生理意义[J]．中华内分泌代谢杂志，2005，21(6)：576～578．
[42] Fu Y, Luo N, Lopes-Virella M F. Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages.[J]. J Lipid Res, 2000, 41(12): 2017～2023.
[43] Qin C, Nagao T, Grosheva I, et al. Elevated plasma membrane cholesterol content alters macrophage signaling and function.[J]. Arterioscler Thromb Vasc Biol, 2006, 26(2): 372～378.
[44] Wang N, Tabas I, Winchester R, et al. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.[J]. J Biol Chem, 1996, 271(15): 8837～8842.
[45] Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.[J]. J Clin Invest, 1998, 101(6): 1354～1361.
[46] 吴凡，屈伸，宗义强．氧化型低密度脂蛋白对巨噬细胞ABCA1表达及功能的影响[J]．华中科技大学学报(医学版)，2006，35(1)：14～17．
[47] Batt K V, Patel L, Botham K M, et al. Chylomicron remnants and oxidised low density lipoprotein have differential effects on the expression of mRNA for genes involved in human macrophage foam cell formation.[J]. J Mol Med, 2004, 82(7): 449～458.
[48] Tang X G. An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport[J]. Proc Natl Acad Sci U S A., 2006, 103(7): 2087～2092.
[49] Porras A, Valladares A, Alvarez A M, et al. Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by TNF-alpha in brown adipocytes.[J]. FEBS Lett, 2002, 520(1-3): 58～62.
[50] Sung C K, She H, Xiong S, et al. Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor gamma activity at a posttranslational level in hepatic stellate cells.[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 286(5): 722～729.
[51] Wang Y, Moser A H, Shigenaga J K, et al. Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines.[J]. J Lipid Res, 2005, 46(11): 2377～2387.
[52] Buechler C, Boettcher A, Bared S M, et al. The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex. [J] . Biochem Biophys Res Commun, 2002, 293(2): 759～765.
[53] Xu J, Fu Y, Chen A. Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth.[J]. Am J Physiol Gastrointest Liver Physiol, 2003, 285(1): 20～30.
[54] Zheng S, Chen A. Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro.[J]. Biochem J, 2004, 384(Pt 1): 149～157.
[55] Kuroda M, Mimaki Y, Nishiyama T, et al. Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice.[J]. Biol Pharm Bull, 2005, 28(5): 937～939.
[56] Pan M H, Lin-Shiau S Y, Lin J K. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.[J]. Biochem Pharmacol, 2000, 60(11): 1665～1676.
[57] 庄向华，许爱梅，周建博．脂肪因子研究新进展[J]．国外医学．内分泌学分册，2004，24(2)：135～136．
[58] Ruby A J, Kuttan G, Babu K D, et al. Anti-tumour and antioxidant activity of natural curcuminoids.[J]. Cancer Lett, 1995, 94(1): 79～83.
[59] Farhangkhoee H, Khan Z A, Chen S, et al. Differential effects of curcumin on vasoactive factors in the diabetic rat heart.[J]. Nutr Metab (Lond), 2006, 3: 27.
[60] BalasubramanyamM,KoteswariAA,KumarRS,etal. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. [J] . J Biosci, 2003, 28(6): 715～721.
[61] Manjunatha H, Srinivasan K. Protective effect of dietary curcumin and capsaicinoninducedoxidationof low-densitylipoprotein,iron-induced hepatotoxicity and carrageenan-induced inflammation in experimental rats.[J]. FEBS J, 2006, 273(19): 4528～4537.
[62] Ahuja K D, Kunde D A, Ball M J, et al. Effects of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation of human serum lipids.[J]. J Agric Food Chem, 2006, 54(17): 6436～6439.
[63] Woo H M, Kang J H, Kawada T, et al. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.[J]. Life Sci, 2007, 80(10): 926～931.
[64] Camacho-Barquero L, Villegas I, Sanchez-Calvo J M, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. [J]. Int Immunopharmacol, 2007, 7(3): 333～342.
[65] Handler N, Jaeger W, Puschacher H, et al. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.[J]. Chem Pharm Bull (Tokyo), 2007, 55(1): 64～71.
[66] Parodi F E, Mao D, Ennis T L, et al. Oral administration of diferuloylmethane(curcumin)suppressesproinflammatorycytokinesand destructive connective tissue remodeling in experimental abdominal aortic aneurysms.[J]. Ann Vasc Surg, 2006, 20(3): 360～368.
[67] Sharma S, Chopra K, Kulkami S K, et al. Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. [J] . Clin Exp Immunol, 2007, 147(1): 155～163.
[68] Kurup V P, Barrios C S, Raju R, et al. Immune response modulation by curcumin in a latex allergy model.[J]. Clin Mol Allergy, 2007, 5: 1.
[69] Pari L, Murugan P. Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats.[J]. J Basic Clin Physiol Pharmacol, 2005, 16(4): 257～274.
[70] Jain S K, Rains J, Jones K. Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels.[J]. Free Radic Biol Med, 2006, 41(1): 92～96.
[71] Ikonomov O C, Sbrissa D, Mlak K, et al. Requirement for PIKfyve enzymatic activity in acute and long-term insulin cellular effects. [J]. Endocrinology, 2002, 143(12): 4742～4754.
[72] Sharma S, Kulkarni S K, Chopra K. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.[J]. Clin Exp Pharmacol Physiol, 2006, 33(10): 940～945.
[73] 杨俊卿，周岐新，李远宗．姜黄提取物对实验性动物高脂血症的防治作用研究[J]．中国药房，2004，15(10)：600～602．
[74] 于冬青，邓华聪．姜黄素对糖尿病大鼠糖、脂代谢及氧化应激的影响[J]．重庆医学，2005，34(1)：37～39．
[75] 高波，范春雷，包瑞梅．姜黄素对巨噬细胞LDL受体表达的影响[J]．浙江中医学院学报，2005，29(1)：45～47．
[76] 王舒然，陈炳卿，孙长颢．姜黄素对大鼠调节血脂及抗氧化作用的研究[J]．卫生研究，2000，29(4)：240～242．
[77] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响[J]．中国动脉硬化杂志，2003，11(3)：223～226．
[78] Shakibaei M, John T, Schulze-Tanzil G, et al. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis.[J]. Biochem Pharmacol, 2007, :
[79] Lin L I, Ke Y F, Ko Y C, et al. Curcumin inhibits SK-Hep-1 hepatocellular carcinoma cell invasion in vitro and suppresses matrix metalloproteinase-9 secretion.[J]. Oncology, 1998,55(4): 349-353.
[80]Liu W H, Chen X M, Fu B. Thrombin stimulates MMP-9 mRNA expression through AP-1 pathway in human mesangial cells. [J]. Acta Pharmacol Sin, 2000, 21(7): 641-645.
[81]Woo M S, Jung S H, Kim S Y, et al. Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells.[J]. Biochem Biophys Res Commun, 2005, 335(4): 1017-1025.
[82]Swarnakar S, Ganguly K, Kundu P, et al. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer.[J]. J Biol Chem, 2005, 280(10): 9409—9415.
[83]Quiles J L, Mesa M D, Ramirez-Tortosa C L, et al. Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits.[J]. Arterioscler Thromb Vasc Biol, 2002, 22(7): 1225—1231.
[84]Olszanecki R, Jawien J, Gajda M, et al. Effect of curcumin on atherosclerosis in apoE/LDLR-double knockout mice.[J], J Physiol Pharmacol, 2005,56(4): 627-635.
[85]Tomas E, Tsao T S, Saha A K, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. [J]. Proc Natl Acad Sci U S A, 2002, 99(25): 16309-16313.
[86] Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.[J]. Nat Med, 2002, 8(11): 1288—1295.
[87]Combs T P, Berg A H, Obici S, et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30.[J]. J Clin Invest, 2001, 108(12): 1875—1881.
[88]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.[J]. Circulation, 2000,102(11): 1296—1301.
[89]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.[J]. Circulation, 2001,103(8): 1057-1063.
[90]Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.[J]. J Biol Chem, 2002, 277(40): 37487-37491.
[91]Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity.[J]. Hypertension, 2003, 42(3): 231-234.
[92]Engeli S, Feldpausch M, Gorzelniak K, et al. Association between adiponectin and mediators of inflammation in obese women.[J]. Diabetes, 2003, 52(4): 942-947.
[93]Iwaki M, Matsuda M, Maeda N, et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.[J]. Diabetes, 2003,52(7): 1655-1663.
[1]Araujo C C, Leon L L. Biological activities of Curcuma longa L.[J]. Mem Inst Oswaldo Cruz, 2001, 96(5): 723-728.
[2]Gukovsky I, Reyes C N, Vaquero E C, et al. Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. [J]. Am J Physiol Gastrointest Liver Physiol, 2003, 284(1): 85-95.
[3]Natarajan C, Bright J J. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes.[J]. J Immunol, 2002,168(12): 6506—6513.
[4]Literat A, Su F, Norwicki M, et al. Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).[J]. Life Sci, 2001, 70(3): 253-267.
[5]Tomita M, Holman B J, Santoro C P, et al. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.[J]. J Neuroinflammation, 2005, 2(1): 8.
[6]Woo H M, Kang J H, Kawada T, et al. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.[J]. Life Sci, 2007, 80(10): 926—931.
[7]Parodi F E, Mao D, Ennis T L, et al. Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms.[J]. Ann Vasc Surg, 2006, 20(3): 360—368.
[8]Pan M H, Lin-Shiau S Y, Lin J K. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.[J]. Biochem Pharmacol, 2000, 60(11): 1665—1676.
[9]Camacho-Barquero L, Villegas I, Sanchez-Calvo J M, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.[J]. Int Immunopharmacol, 2007, 7(3): 333-342.
[10]Handler N, Jaeger W, Puschacher H, et al. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.[J]. Chem Pharrn Bull (Tokyo), 2007, 55(1): 64～71.
[11] Kim H Y, Park E J, Joe E H, et al. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia.[J]. J Immunol, 2003, 171(11): 6072～6079.
[12] Korutla L, Cheung J Y, Mendelsohn J, et al. Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin.[J]. Carcinogenesis, 1995, 16(8): 1741～1745.
[13] Joe B, Lokesh B R. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages.[J]. Biochim Biophys Acta, 1994, 1224(2): 255～263.
[14] Brouet I,Ohshima H.Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages.[J]. Biochem Biophys Res Commun, 1995, 206(2): 533～540.
[15] Ramirez-Tortosa M C, Mesa M D, Aguilera M C, et al. Oral administrationof aturmericextractinhibitsLDLoxidationandhas hypocholesterolemic effects in rabbits with experimental atherosclerosis.[J]. Atherosclerosis, 1999, 147(2): 371～378.
[16] 杨俊卿，周岐新，李远宗．姜黄提取物对实验性动物高脂血症的防治作用研究[J]．中国药房，2004，15(10)：600～602．
[17] 王舒然，陈炳卿，王朝旭等．姜黄素降血脂及抗氧化作用的研究[J]．中国公共卫生学报，1999，18(5)：263～265．
[18] 石晶，王中孝，田亚平等．姜黄素对高脂血症大鼠血浆和肝脏超氧化物歧化酶和脂质过氧化物的影响[J]．中草药，1997，28(5)：285～287。
[19] 王舒然，陈炳卿，孙长颢．姜黄素对大鼠调节血脂及抗氧化作用的研究[J]．卫生研究，2000，29(4)：240～242．
[20] 潘赞红，李薇，金鑫．姜黄素对高脂血症动物的实验研究[J]．天津中医，1999，16(5)：35～36．
[21] 沃兴德，洪行球，赵革平等．姜黄素对低密度脂蛋白和脂蛋白(a)代谢的影响[J]．中国动脉硬化杂志，1999，7(4)：339～341．
[22] Asai A, Miyazawa T. Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue.[J]. J Nutr, 2001, 131(11)：2932～2935．
[23] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响[J]．中国动脉硬化杂志，2003，11(3)：223～226．
[24] Arafa H M. Curcumin attenuates diet-induced hypercholesterolemia inrats.[J]. Med Sci Monit, 2005, 11(7): 228～234.
[25] 于冬青，邓华聪．姜黄素对糖尿病大鼠糖、脂代谢及氧化应激的影响[J]．重庆医学，2005，34(1)：37～39．
[26] Babu P S, Srinivasan K. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats.[J]. Mol Cell Biochem, 1997, 166(1-2): 169～175.
[27] Rukkumani R, Aruna K, Varma PS E A. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid- induced alteration in circulatory lipid profiles[J]. J Med Food., 2005, 8(2): 256～260.
[28] 高波，范春雷，包瑞梅．姜黄素对巨噬细胞LDL受体表达的影响[J]．浙江中医学院学报，2005，29(1)：45～47．
[29] 范春雷，沃兴德，罗艳等．姜黄素对爪蟾卵母细胞表达人低密度脂蛋白受体的影响[J]．中国中西医结合杂志，2005，25(5)：432～435．
[30] 肖小河，罗泽渊．姜黄属药用植物研究进展[J]．中草药，1997，28(2)：114～119
[31] Deters M, Klabunde T, Meyer H, et al. Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat.[J]. Planta Med, 2003, 69(4): 337～343.
[32] Hayes K C, Pronczuk A, Wijendran V, et al. Free phytosterols facilitate excretion of endogenous cholesterol in gerbils.[J]. J Nutr Biochem, 2005, 16(5): 305～311.
[33] Srinivasan K, Sambaiah K. The effect of spices on cholesterol 7 alpha-hydroxylase. activity and on serum and hepatic cholesterol levels in the rat.[J]. Int J Vitam Nutr Res, 1991, 61(4): 364～369.
[34] Soni K B, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. [J] . Indian J Physiol Pharmacol, 1992, 36(4): 273～275.
[35] 杜宝俊，涂秀华，李立志．脂可平软胶囊治疗高脂血症临床研究[J]．中国中医药信息杂志，2004，11(9)：757～759．
[1]Thielmann M, Dorge H, Martin C, et al. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine.[J]. Circ Res, 2002, 90(7): 807—813.
[2]Tartaglia L A, Weber R F, Figari I S, et al. The two different receptors for tumor necrosis factor mediate distinct cellular responses. [J]. Proc Natl Acad Sci U S A, 1991, 88(20): 9292-9296.
[3]Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.[J]. Nature, 1993,362(6423): 801-809.
[4]Barath P, Fishbein M C, Cao J, et al. Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization.[J]. Am J Pathol, 1990,137(3): 503-509.
[5]Tipping P G, Hancock W W. Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques.[J]. Am J Pathol, 1993,142(6): 1721-1728.
[6]Boesten L S, Zadelaar A S, van N A, et al. Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice.[J]. Cardiovasc Res, 2005, 66(1): 179—185.
[7]Canault M, Peiretti F, Mueller C, et al. Exclusive expression of transmembrane TNF-alpha in mice reduces the inflammatory response in early lipid lesions of aortic sinus.[J]. Atherosclerosis, 2004,172(2): 211—218.
[8]Mizia-Stec K, Gasior Z, Zahorska-Markiewicz B, et al. Serum tumour necrosis factor-alpha, interleukin-2 and interleukin-10 activation in stable angina and acute coronary syndromes.[J]. Coron Artery Dis, 2003,14(6): 431—438.
[9]Sukhija R, Fahdi I, Garza L, et al. Inflammatory markers, angiographic severity of coronary artery disease, and patient outcome.[J]. Am J Cardiol, 2007, 99(7): 879-884.
[10]Brett J, Gerlach H, Nawroth P, et al. Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins.[J]. J Exp Med, 1989,169(6): 1977—1991.
[11]Stolpen A H, Guinan E C, Fiers W, et al. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers.[J]. Am J Pathol, 1986,123(1): 16—24.
[12]Nakashima Y, Raines E W, Plump A S, et al. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse.[J]. Arterioscler Thromb Vasc Biol, 1998,18(5): 842-851.
[13]Osborn L, Hession C, Tizard R, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.[J]. Cell, 1989,59(6): 1203-1211.
[14]Mackay F, Loetscher H, Stueber D, et al. Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.[J]. J Exp Med, 1993, 177(5): 1277~ 1286.
[15]Myers C L, Wertheimer S J, Schembri-King J, et al. Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC.[J]. Am J Physiol, 1992, 263(4 Pt 1): 767-772.
[16]Wertheimer S J, Myers C L, Wallace R W, et al. Intercellular adhesion molecule-1 gene expression in human endothelial cells. Differential regulation by tumor necrosis factor-alpha and phorbol myristate acetate.[J]. J Biol Chem, 1992, 267(17): 12030-12035.
[17]Roebuck K A, Rahman A, Lakshminarayanan V, et al. H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter.[J]. J Biol Chem, 1995, 270(32): 18966-18974.
[18]Couffinhal T, Duplaa C, Labat L, et al. Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells.[J]. Arterioscler Thromb, 1993,13(3): 407-414.
[19]Barks J L, McQuillan J J, Iademarco M F. TNF-alpha and IL-4 synergistically increase vascular cell adhesion molecule-1 expression in cultured vascular smooth muscle cells.[J]. J Immunol, 1997,159(9): 4532-4538.
[20]Ohta H, Wada H, Niwa T, et al. Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice.[J]. Atherosclerosis, 2005,180(1): 11-17.
[21]Jovinge S, Hultgardh-Nilsson A, Regnstrom J, et al. Tumor necrosis factor-alpha activates smooth muscle cell migration in culture and is expressed in the balloon-injured rat aorta.[J]. Arterioscler Thromb Vasc Biol, 1997,17(3): 490-497.
[22]Goetze S, Xi X P, Kawano Y, et al. TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent.[J]. Hypertension, 1999,33(1 Pt 2): 183-189.
[23]Ming W J, Bersani L, Mantovani A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes.[J]. J Immunol, 1987, 138(5): 1469- 1474.
[24]Li H, Freeman M W, Libby P. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines.[J]. J Clin Invest, 1995, 95(1): 122-133.
[25]van L B, Fogelman A M. Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha.[J]. J Immunol, 1992,148(1): 112-116.
[26]Hsu H Y, Nicholson A C, Hajjar D P. Inhibition of macrophage scavenger receptor activity by tumor necrosis factor-alpha is transcriptionally and post-transcriptionally regulated.[J]. J Biol Chem, 1996, 271(13): 7767-7773.
[27]Sawdey M, Podor T J, Loskutoff D J. Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells. Induction by transforming growth factor-beta, lipopolysaccharide, and tumor necrosis factor-alpha.[J]. J Biol Chem, 1989, 264(18): 10396-10401.
[28] Gu L, Okada Y, Clinton S K, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.[J]. Mol Cell, 1998, 2(2): 275-281.
[29]Boring L, Gosling J, Cleary M, et al. Decreased lesion formation in CCR2-/-mice reveals a role for Chemokines in the initiation of atherosclerosis.[J]. Nature, 1998, 394(6696): 894-897.
[30]Rollins B J, Yoshimura T, Leonard E J, et al. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE.[J]. Am J Pathol, 1990,136(6): 1229-1233.
[31]Yeh M, Leitinger N, de M R, et al. Increased transcription of IL-8 in endothelial cells is differentially regulated by TNF-alpha and oxidized phospholipids.[J] . Arterioscler Thromb Vasc Biol, 2001, 21(10): 1585-1591.
[32]van W A, Becker A E, van L C, et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.[J]. Circulation, 1994, 89(1): 36-44.
[33] Kovanen P T, Kaartinen M, Paavonen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. [J]. Circulation, 1995, 92(5): 1084～1088.
[34] Kaartinen M, Penttila A, Kovanen P T. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha.[J]. Circulation, 1996, 94(11): 2787～2792.
[35] Saren P, Welgus H G, Kovanen P T. TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages.[J]. J Immunol, 1996, 157(9): 4159～4165.
[36] Moon S K, Cha B Y, Kim C H. ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway. [J]. J Cell Physiol, 2004, 198(3): 417～427.
[37] Tang V, Dhirapong A, Yabes A P, et al. TNF-alpha-mediated apoptosis in vascular smooth muscle cells requires p73.[J]. Am J Physiol Cell Physiol, 2005, 289(1): 199～206.
[38] 余丹青，陈纪言，周颖玲等．冠脉斑块稳定性与肿瘤坏死因子相关研究[J]．岭南心血管病杂志，2002，8(5)：332～335．
[39] Schreyer S A, Peschon J J, LeBoeuf R C. Accelerated atherosclerosis in mice lacking tumor necrosis factor receptor p55.[J]. J Biol Chem, 1996, 271(42): 26174～26178.
[40] Schreyer S A, Vick C M, LeBoeuf R C. Loss of lymphotoxin-alpha but not tumor necrosis factor-alpha reduces atherosclerosis in mice.[J]. J Biol Chem, 2002, 277(14): 12364～12368.
[41] Hansen P R, Chew M, Zhou J, et al. Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNFalpha confers no additional benefit.[J]. Atherosclerosis, 2001, 158(1): 87～94.
[42] Elhage R, Maret A, Pieraggi M T, et al. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice.[J]. Circulation, 1998, 97(3): 242～244.
[2]Skurk T, Alberti-Huber C, Herder C, et al. Relationship between adipocyte size and adipokine expression and secretion.[J]. J Clin Endocrinol Metab, 2006,:
[3]Murdolo G, Smith U. The dysregulated adipose tissue: A connecting link between insulin resistance, type 2 diabetes mellitus and atherosclerosis.[J]. Nutr Metab Cardiovasc Dis, 2006,16S1: 35—38.
[4]Le L S, Robichon C, Le X, et al. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells[J]. J.Lipid Res., 2003,44:1499-1507.
[5]Van G L, Mertens I L, De B C. Mechanisms linking obesity with cardiovascular disease.[J]. Nature, 2006,444(7121): 875~880.
[6]Berg A H, Scherer P E. Adipose tissue, inflammation, and cardiovascular disease.[J]. Circ Res, 2005, 96(9): 939-949.
[7]Ruan H, Lodish H F. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha.[J]. Cytokine Growth Factor Rev, 2003,14(5): 447-455.
[8]Uysal K T, Wiesbrock S M, Marino M W, et al. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function.[J]. Nature, 1997, 389(6651): 610-614.
[9]Bouloumie A, Curat C A, Sengenes C, et al. Role of macrophage tissue infiltration in metabolic diseases.[J]. Curr Opin Clin Nutr Metab Care, 2005, 8(4): 347-354.
[10]Xu H, Barnes G T, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.[J]. J Clin Invest, 2003,112(12): 1821—1830.
[11]Weisberg S P, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue.[J]. J Clin Invest, 2003, 112(12): 1796-1808.
[12]Ruan H, Hacohen N, Golub T R, et al. Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.[J]. Diabetes, 2002, 51(5): 1319～1336.
[13] Lee J Y, Plakidas A, Lee W H, et al. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.[J]. J Lipid Res, 2003, 44(3): 479～486.
[14] Suganami T, Nishida J, Ogawa Y. A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes Role of Free Fatty Acids and Tumor Necrosis Factor α[J]. Arterioscler Thromb Vasc Biol., 2005, 25: 0～0.
[15] Wang B, Jenkins J R, Trayhurn P. Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha.[J]. Am J Physiol Endocrinol Metab, 2005, 288(4): 731～740.
[16] Kim K Y, Kim J K, Jeon J H, et al. c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes.[J]. Biochem Biophys Res Commun, 2005, 327(2): 460～467.
[17] 杨再刚，张木勋，许莉军，et al. Effect of Tumor Necrosis Factor-α on Resistin Expression in 3T3-L1 Adipocytes and Its Mechanism[J]．华中科技大学学报(医学英德文版)，2005，25(02)：121～130．
[18] Shojima N, Sakoda H, Ogihara T, et al. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells.[J]. Diabetes, 2002, 51(6): 1737～1744.
[19] Wang B, Trayhurn P. Acute and prolonged effects of TNF-alpha on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture. [J]. Pflugers Arch, 2006, 452(4): 418～427.
[20] Kirchgessner T G, Uysal K T, Wiesbrock S M, et al. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes.[J]. J Clin Invest, 1997, 100(11): 2777～2782.
[21] Xu G R, Li H, Pan L X, et al. FXR-mediated down-regulation of CYP7A1 dominates LXR in long-term cholesterol-fed NZW rabbits[J]. J. Lipid Res, 2003, 44: 1956—1962.
[22] Liver X receptor-α mediates cholesterol efflux in glomerular mesangial cells[J]. Am J Physiol Renal Physiol, 2004, :
[23] Neufeld E B, Remaley A T, Demosky S J, et al. Cellular localization and trafficking of the human ABCA1 transporter.[J]. J Biol Chem, 2001, 276(29): 27584～27590.
[24] 许竹梅，赵水平．ATP结合盒转运子调节细胞内胆固醇流出及对动脉粥样硬化的影响[J]．中国动脉硬化杂志，2002，10(5)：449．
[25] Ruan H, Miles P D, Ladd C M, et al. Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance.[J]. Diabetes, 2002, 51(11): 3176～3188.
[26] Rieusset J, Andreelli F, Auboeuf D, et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes.[J]. Diabetes, 1999, 48(4): 699～705.
[27] Nagy L, Tontonoz P, Alvarez J G, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma.[J]. Cell, 1998, 93(2): 229～240.
[28] 王浩，杨晔．PPARγ PPARγ配体TZDs与高血压[J]．心肺血管病杂志，2005，(04)：245～246249.
[29] Chambrier C, Bastard J P, Rieusset J, et al. Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma.[J]. Obes Res, 2002, 10(6): 518～525.
[30] ChinettiG,GriglioS,AntonucciM,etal.Activationof proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages.[J]. J Biol Chem, 1998, 273(40): 25573～25580.
[31] 刘东，曾邦雄，张世范．过氧化物酶体增殖物激活受体γ与脓毒症的关系[J]．中国危重病急救医学，2005，(04)：244～246．
[32] Davies J D, Carpenter K L, Challis I R, et al. Adipocytic differentiation and liver x receptor pathways regulate the accumulation of triacylglycerols in human vascular smooth muscle cells.[J]. J Biol Chem, 2005, 280(5): 3911～3919.
[33] Seo J B, Moon H M, Kim W S, et alo Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferator-activated receptor gamma expression. [J]. Mol Cell Biol, 2004, 24(8): 3430～3444.
[34] Gerbod-Giannone M C, Li Y, Holleboom A, et al. TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells.[J]. Proc Natl Acad Sci U S A, 2006, 103(9): 3112～3117.
[35] Zhang B, Berger J, Hu E, et al. Negative regulation of peroxisome proliferator-activatedreceptor-gammageneexpressioncontributestothe antiadipogenic effects of tumor necrosis factor-alpha.[J]. Mol Endocrinol, 1996, 10(11): 1457～1466.
[36] Bastard J P, Hainque B, Dusserre E, et al. Peroxisome proliferator activated receptor-gamma, leptin and tumor necrosis factor-alpha mRNA expression during very low calorie diet in subcutaneous adipose tissue in obese women.[J]. Diabetes Metab Res Rev, 1999, 15(2): 92～98.
[37] Wang X, Sato R, Brown M S, et al. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.[J]. Cell, 1994, 77(1): 53～62.
[38] Rosen E D, Walkey C J, Puigserver P, et al. Transcriptional regulation of adipogenesis.[J]. Genes Dev, 2000, 14(11): 1293～1307.
[39] Sewter C, Berger D, Considine R V, et al. Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha.[J]. Diabetes, 2002, 51(4): 1035～1041.
[40] Prins J B, Niesler C U, Winterford C M, et al. Tumor necrosis factor-alpha induces apoptosis of human adipose cells.[J]. Diabetes, 1997, 46(12): 1939～1944.
[41] 吴智鸿，赵水平．脂肪细胞胆固醇代谢及其病理生理意义[J]．中华内分泌代谢杂志，2005，21(6)：576～578．
[42] Fu Y, Luo N, Lopes-Virella M F. Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages.[J]. J Lipid Res, 2000, 41(12): 2017～2023.
[43] Qin C, Nagao T, Grosheva I, et al. Elevated plasma membrane cholesterol content alters macrophage signaling and function.[J]. Arterioscler Thromb Vasc Biol, 2006, 26(2): 372～378.
[44] Wang N, Tabas I, Winchester R, et al. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.[J]. J Biol Chem, 1996, 271(15): 8837～8842.
[45] Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.[J]. J Clin Invest, 1998, 101(6): 1354～1361.
[46] 吴凡，屈伸，宗义强．氧化型低密度脂蛋白对巨噬细胞ABCA1表达及功能的影响[J]．华中科技大学学报(医学版)，2006，35(1)：14～17．
[47] Batt K V, Patel L, Botham K M, et al. Chylomicron remnants and oxidised low density lipoprotein have differential effects on the expression of mRNA for genes involved in human macrophage foam cell formation.[J]. J Mol Med, 2004, 82(7): 449～458.
[48] Tang X G. An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport[J]. Proc Natl Acad Sci U S A., 2006, 103(7): 2087～2092.
[49] Porras A, Valladares A, Alvarez A M, et al. Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by TNF-alpha in brown adipocytes.[J]. FEBS Lett, 2002, 520(1-3): 58～62.
[50] Sung C K, She H, Xiong S, et al. Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor gamma activity at a posttranslational level in hepatic stellate cells.[J]. Am J Physiol Gastrointest Liver Physiol, 2004, 286(5): 722～729.
[51] Wang Y, Moser A H, Shigenaga J K, et al. Downregulation of liver X receptor-alpha in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines.[J]. J Lipid Res, 2005, 46(11): 2377～2387.
[52] Buechler C, Boettcher A, Bared S M, et al. The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex. [J] . Biochem Biophys Res Commun, 2002, 293(2): 759～765.
[53] Xu J, Fu Y, Chen A. Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth.[J]. Am J Physiol Gastrointest Liver Physiol, 2003, 285(1): 20～30.
[54] Zheng S, Chen A. Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro.[J]. Biochem J, 2004, 384(Pt 1): 149～157.
[55] Kuroda M, Mimaki Y, Nishiyama T, et al. Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice.[J]. Biol Pharm Bull, 2005, 28(5): 937～939.
[56] Pan M H, Lin-Shiau S Y, Lin J K. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.[J]. Biochem Pharmacol, 2000, 60(11): 1665～1676.
[57] 庄向华，许爱梅，周建博．脂肪因子研究新进展[J]．国外医学．内分泌学分册，2004，24(2)：135～136．
[58] Ruby A J, Kuttan G, Babu K D, et al. Anti-tumour and antioxidant activity of natural curcuminoids.[J]. Cancer Lett, 1995, 94(1): 79～83.
[59] Farhangkhoee H, Khan Z A, Chen S, et al. Differential effects of curcumin on vasoactive factors in the diabetic rat heart.[J]. Nutr Metab (Lond), 2006, 3: 27.
[60] BalasubramanyamM,KoteswariAA,KumarRS,etal. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. [J] . J Biosci, 2003, 28(6): 715～721.
[61] Manjunatha H, Srinivasan K. Protective effect of dietary curcumin and capsaicinoninducedoxidationof low-densitylipoprotein,iron-induced hepatotoxicity and carrageenan-induced inflammation in experimental rats.[J]. FEBS J, 2006, 273(19): 4528～4537.
[62] Ahuja K D, Kunde D A, Ball M J, et al. Effects of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation of human serum lipids.[J]. J Agric Food Chem, 2006, 54(17): 6436～6439.
[63] Woo H M, Kang J H, Kawada T, et al. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.[J]. Life Sci, 2007, 80(10): 926～931.
[64] Camacho-Barquero L, Villegas I, Sanchez-Calvo J M, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. [J]. Int Immunopharmacol, 2007, 7(3): 333～342.
[65] Handler N, Jaeger W, Puschacher H, et al. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.[J]. Chem Pharm Bull (Tokyo), 2007, 55(1): 64～71.
[66] Parodi F E, Mao D, Ennis T L, et al. Oral administration of diferuloylmethane(curcumin)suppressesproinflammatorycytokinesand destructive connective tissue remodeling in experimental abdominal aortic aneurysms.[J]. Ann Vasc Surg, 2006, 20(3): 360～368.
[67] Sharma S, Chopra K, Kulkami S K, et al. Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. [J] . Clin Exp Immunol, 2007, 147(1): 155～163.
[68] Kurup V P, Barrios C S, Raju R, et al. Immune response modulation by curcumin in a latex allergy model.[J]. Clin Mol Allergy, 2007, 5: 1.
[69] Pari L, Murugan P. Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats.[J]. J Basic Clin Physiol Pharmacol, 2005, 16(4): 257～274.
[70] Jain S K, Rains J, Jones K. Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels.[J]. Free Radic Biol Med, 2006, 41(1): 92～96.
[71] Ikonomov O C, Sbrissa D, Mlak K, et al. Requirement for PIKfyve enzymatic activity in acute and long-term insulin cellular effects. [J]. Endocrinology, 2002, 143(12): 4742～4754.
[72] Sharma S, Kulkarni S K, Chopra K. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.[J]. Clin Exp Pharmacol Physiol, 2006, 33(10): 940～945.
[73] 杨俊卿，周岐新，李远宗．姜黄提取物对实验性动物高脂血症的防治作用研究[J]．中国药房，2004，15(10)：600～602．
[74] 于冬青，邓华聪．姜黄素对糖尿病大鼠糖、脂代谢及氧化应激的影响[J]．重庆医学，2005，34(1)：37～39．
[75] 高波，范春雷，包瑞梅．姜黄素对巨噬细胞LDL受体表达的影响[J]．浙江中医学院学报，2005，29(1)：45～47．
[76] 王舒然，陈炳卿，孙长颢．姜黄素对大鼠调节血脂及抗氧化作用的研究[J]．卫生研究，2000，29(4)：240～242．
[77] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响[J]．中国动脉硬化杂志，2003，11(3)：223～226．
[78] Shakibaei M, John T, Schulze-Tanzil G, et al. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis.[J]. Biochem Pharmacol, 2007, :
[79] Lin L I, Ke Y F, Ko Y C, et al. Curcumin inhibits SK-Hep-1 hepatocellular carcinoma cell invasion in vitro and suppresses matrix metalloproteinase-9 secretion.[J]. Oncology, 1998,55(4): 349-353.
[80]Liu W H, Chen X M, Fu B. Thrombin stimulates MMP-9 mRNA expression through AP-1 pathway in human mesangial cells. [J]. Acta Pharmacol Sin, 2000, 21(7): 641-645.
[81]Woo M S, Jung S H, Kim S Y, et al. Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells.[J]. Biochem Biophys Res Commun, 2005, 335(4): 1017-1025.
[82]Swarnakar S, Ganguly K, Kundu P, et al. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer.[J]. J Biol Chem, 2005, 280(10): 9409—9415.
[83]Quiles J L, Mesa M D, Ramirez-Tortosa C L, et al. Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits.[J]. Arterioscler Thromb Vasc Biol, 2002, 22(7): 1225—1231.
[84]Olszanecki R, Jawien J, Gajda M, et al. Effect of curcumin on atherosclerosis in apoE/LDLR-double knockout mice.[J], J Physiol Pharmacol, 2005,56(4): 627-635.
[85]Tomas E, Tsao T S, Saha A K, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. [J]. Proc Natl Acad Sci U S A, 2002, 99(25): 16309-16313.
[86] Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.[J]. Nat Med, 2002, 8(11): 1288—1295.
[87]Combs T P, Berg A H, Obici S, et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30.[J]. J Clin Invest, 2001, 108(12): 1875—1881.
[88]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.[J]. Circulation, 2000,102(11): 1296—1301.
[89]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.[J]. Circulation, 2001,103(8): 1057-1063.
[90]Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis.[J]. J Biol Chem, 2002, 277(40): 37487-37491.
[91]Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity.[J]. Hypertension, 2003, 42(3): 231-234.
[92]Engeli S, Feldpausch M, Gorzelniak K, et al. Association between adiponectin and mediators of inflammation in obese women.[J]. Diabetes, 2003, 52(4): 942-947.
[93]Iwaki M, Matsuda M, Maeda N, et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors.[J]. Diabetes, 2003,52(7): 1655-1663.
[1]Araujo C C, Leon L L. Biological activities of Curcuma longa L.[J]. Mem Inst Oswaldo Cruz, 2001, 96(5): 723-728.
[2]Gukovsky I, Reyes C N, Vaquero E C, et al. Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. [J]. Am J Physiol Gastrointest Liver Physiol, 2003, 284(1): 85-95.
[3]Natarajan C, Bright J J. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes.[J]. J Immunol, 2002,168(12): 6506—6513.
[4]Literat A, Su F, Norwicki M, et al. Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).[J]. Life Sci, 2001, 70(3): 253-267.
[5]Tomita M, Holman B J, Santoro C P, et al. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.[J]. J Neuroinflammation, 2005, 2(1): 8.
[6]Woo H M, Kang J H, Kawada T, et al. Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.[J]. Life Sci, 2007, 80(10): 926—931.
[7]Parodi F E, Mao D, Ennis T L, et al. Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms.[J]. Ann Vasc Surg, 2006, 20(3): 360—368.
[8]Pan M H, Lin-Shiau S Y, Lin J K. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.[J]. Biochem Pharmacol, 2000, 60(11): 1665—1676.
[9]Camacho-Barquero L, Villegas I, Sanchez-Calvo J M, et al. Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.[J]. Int Immunopharmacol, 2007, 7(3): 333-342.
[10]Handler N, Jaeger W, Puschacher H, et al. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.[J]. Chem Pharrn Bull (Tokyo), 2007, 55(1): 64～71.
[11] Kim H Y, Park E J, Joe E H, et al. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia.[J]. J Immunol, 2003, 171(11): 6072～6079.
[12] Korutla L, Cheung J Y, Mendelsohn J, et al. Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin.[J]. Carcinogenesis, 1995, 16(8): 1741～1745.
[13] Joe B, Lokesh B R. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages.[J]. Biochim Biophys Acta, 1994, 1224(2): 255～263.
[14] Brouet I,Ohshima H.Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages.[J]. Biochem Biophys Res Commun, 1995, 206(2): 533～540.
[15] Ramirez-Tortosa M C, Mesa M D, Aguilera M C, et al. Oral administrationof aturmericextractinhibitsLDLoxidationandhas hypocholesterolemic effects in rabbits with experimental atherosclerosis.[J]. Atherosclerosis, 1999, 147(2): 371～378.
[16] 杨俊卿，周岐新，李远宗．姜黄提取物对实验性动物高脂血症的防治作用研究[J]．中国药房，2004，15(10)：600～602．
[17] 王舒然，陈炳卿，王朝旭等．姜黄素降血脂及抗氧化作用的研究[J]．中国公共卫生学报，1999，18(5)：263～265．
[18] 石晶，王中孝，田亚平等．姜黄素对高脂血症大鼠血浆和肝脏超氧化物歧化酶和脂质过氧化物的影响[J]．中草药，1997，28(5)：285～287。
[19] 王舒然，陈炳卿，孙长颢．姜黄素对大鼠调节血脂及抗氧化作用的研究[J]．卫生研究，2000，29(4)：240～242．
[20] 潘赞红，李薇，金鑫．姜黄素对高脂血症动物的实验研究[J]．天津中医，1999，16(5)：35～36．
[21] 沃兴德，洪行球，赵革平等．姜黄素对低密度脂蛋白和脂蛋白(a)代谢的影响[J]．中国动脉硬化杂志，1999，7(4)：339～341．
[22] Asai A, Miyazawa T. Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue.[J]. J Nutr, 2001, 131(11)：2932～2935．
[23] 沃兴德，崔小强，唐利华．姜黄素对食饵性高脂血症大鼠血浆脂蛋白代谢相关酶活性的影响[J]．中国动脉硬化杂志，2003，11(3)：223～226．
[24] Arafa H M. Curcumin attenuates diet-induced hypercholesterolemia inrats.[J]. Med Sci Monit, 2005, 11(7): 228～234.
[25] 于冬青，邓华聪．姜黄素对糖尿病大鼠糖、脂代谢及氧化应激的影响[J]．重庆医学，2005，34(1)：37～39．
[26] Babu P S, Srinivasan K. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats.[J]. Mol Cell Biochem, 1997, 166(1-2): 169～175.
[27] Rukkumani R, Aruna K, Varma PS E A. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid- induced alteration in circulatory lipid profiles[J]. J Med Food., 2005, 8(2): 256～260.
[28] 高波，范春雷，包瑞梅．姜黄素对巨噬细胞LDL受体表达的影响[J]．浙江中医学院学报，2005，29(1)：45～47．
[29] 范春雷，沃兴德，罗艳等．姜黄素对爪蟾卵母细胞表达人低密度脂蛋白受体的影响[J]．中国中西医结合杂志，2005，25(5)：432～435．
[30] 肖小河，罗泽渊．姜黄属药用植物研究进展[J]．中草药，1997，28(2)：114～119
[31] Deters M, Klabunde T, Meyer H, et al. Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat.[J]. Planta Med, 2003, 69(4): 337～343.
[32] Hayes K C, Pronczuk A, Wijendran V, et al. Free phytosterols facilitate excretion of endogenous cholesterol in gerbils.[J]. J Nutr Biochem, 2005, 16(5): 305～311.
[33] Srinivasan K, Sambaiah K. The effect of spices on cholesterol 7 alpha-hydroxylase. activity and on serum and hepatic cholesterol levels in the rat.[J]. Int J Vitam Nutr Res, 1991, 61(4): 364～369.
[34] Soni K B, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. [J] . Indian J Physiol Pharmacol, 1992, 36(4): 273～275.
[35] 杜宝俊，涂秀华，李立志．脂可平软胶囊治疗高脂血症临床研究[J]．中国中医药信息杂志，2004，11(9)：757～759．
[1]Thielmann M, Dorge H, Martin C, et al. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine.[J]. Circ Res, 2002, 90(7): 807—813.
[2]Tartaglia L A, Weber R F, Figari I S, et al. The two different receptors for tumor necrosis factor mediate distinct cellular responses. [J]. Proc Natl Acad Sci U S A, 1991, 88(20): 9292-9296.
[3]Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.[J]. Nature, 1993,362(6423): 801-809.
[4]Barath P, Fishbein M C, Cao J, et al. Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization.[J]. Am J Pathol, 1990,137(3): 503-509.
[5]Tipping P G, Hancock W W. Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques.[J]. Am J Pathol, 1993,142(6): 1721-1728.
[6]Boesten L S, Zadelaar A S, van N A, et al. Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice.[J]. Cardiovasc Res, 2005, 66(1): 179—185.
[7]Canault M, Peiretti F, Mueller C, et al. Exclusive expression of transmembrane TNF-alpha in mice reduces the inflammatory response in early lipid lesions of aortic sinus.[J]. Atherosclerosis, 2004,172(2): 211—218.
[8]Mizia-Stec K, Gasior Z, Zahorska-Markiewicz B, et al. Serum tumour necrosis factor-alpha, interleukin-2 and interleukin-10 activation in stable angina and acute coronary syndromes.[J]. Coron Artery Dis, 2003,14(6): 431—438.
[9]Sukhija R, Fahdi I, Garza L, et al. Inflammatory markers, angiographic severity of coronary artery disease, and patient outcome.[J]. Am J Cardiol, 2007, 99(7): 879-884.
[10]Brett J, Gerlach H, Nawroth P, et al. Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins.[J]. J Exp Med, 1989,169(6): 1977—1991.
[11]Stolpen A H, Guinan E C, Fiers W, et al. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers.[J]. Am J Pathol, 1986,123(1): 16—24.
[12]Nakashima Y, Raines E W, Plump A S, et al. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse.[J]. Arterioscler Thromb Vasc Biol, 1998,18(5): 842-851.
[13]Osborn L, Hession C, Tizard R, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.[J]. Cell, 1989,59(6): 1203-1211.
[14]Mackay F, Loetscher H, Stueber D, et al. Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.[J]. J Exp Med, 1993, 177(5): 1277~ 1286.
[15]Myers C L, Wertheimer S J, Schembri-King J, et al. Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC.[J]. Am J Physiol, 1992, 263(4 Pt 1): 767-772.
[16]Wertheimer S J, Myers C L, Wallace R W, et al. Intercellular adhesion molecule-1 gene expression in human endothelial cells. Differential regulation by tumor necrosis factor-alpha and phorbol myristate acetate.[J]. J Biol Chem, 1992, 267(17): 12030-12035.
[17]Roebuck K A, Rahman A, Lakshminarayanan V, et al. H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter.[J]. J Biol Chem, 1995, 270(32): 18966-18974.
[18]Couffinhal T, Duplaa C, Labat L, et al. Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells.[J]. Arterioscler Thromb, 1993,13(3): 407-414.
[19]Barks J L, McQuillan J J, Iademarco M F. TNF-alpha and IL-4 synergistically increase vascular cell adhesion molecule-1 expression in cultured vascular smooth muscle cells.[J]. J Immunol, 1997,159(9): 4532-4538.
[20]Ohta H, Wada H, Niwa T, et al. Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice.[J]. Atherosclerosis, 2005,180(1): 11-17.
[21]Jovinge S, Hultgardh-Nilsson A, Regnstrom J, et al. Tumor necrosis factor-alpha activates smooth muscle cell migration in culture and is expressed in the balloon-injured rat aorta.[J]. Arterioscler Thromb Vasc Biol, 1997,17(3): 490-497.
[22]Goetze S, Xi X P, Kawano Y, et al. TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent.[J]. Hypertension, 1999,33(1 Pt 2): 183-189.
[23]Ming W J, Bersani L, Mantovani A. Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leukocytes.[J]. J Immunol, 1987, 138(5): 1469- 1474.
[24]Li H, Freeman M W, Libby P. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines.[J]. J Clin Invest, 1995, 95(1): 122-133.
[25]van L B, Fogelman A M. Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha.[J]. J Immunol, 1992,148(1): 112-116.
[26]Hsu H Y, Nicholson A C, Hajjar D P. Inhibition of macrophage scavenger receptor activity by tumor necrosis factor-alpha is transcriptionally and post-transcriptionally regulated.[J]. J Biol Chem, 1996, 271(13): 7767-7773.
[27]Sawdey M, Podor T J, Loskutoff D J. Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells. Induction by transforming growth factor-beta, lipopolysaccharide, and tumor necrosis factor-alpha.[J]. J Biol Chem, 1989, 264(18): 10396-10401.
[28] Gu L, Okada Y, Clinton S K, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.[J]. Mol Cell, 1998, 2(2): 275-281.
[29]Boring L, Gosling J, Cleary M, et al. Decreased lesion formation in CCR2-/-mice reveals a role for Chemokines in the initiation of atherosclerosis.[J]. Nature, 1998, 394(6696): 894-897.
[30]Rollins B J, Yoshimura T, Leonard E J, et al. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE.[J]. Am J Pathol, 1990,136(6): 1229-1233.
[31]Yeh M, Leitinger N, de M R, et al. Increased transcription of IL-8 in endothelial cells is differentially regulated by TNF-alpha and oxidized phospholipids.[J] . Arterioscler Thromb Vasc Biol, 2001, 21(10): 1585-1591.
[32]van W A, Becker A E, van L C, et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology.[J]. Circulation, 1994, 89(1): 36-44.
[33] Kovanen P T, Kaartinen M, Paavonen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. [J]. Circulation, 1995, 92(5): 1084～1088.
[34] Kaartinen M, Penttila A, Kovanen P T. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha.[J]. Circulation, 1996, 94(11): 2787～2792.
[35] Saren P, Welgus H G, Kovanen P T. TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages.[J]. J Immunol, 1996, 157(9): 4159～4165.
[36] Moon S K, Cha B Y, Kim C H. ERK1/2 mediates TNF-alpha-induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-kappaB and AP-1: Involvement of the ras dependent pathway. [J]. J Cell Physiol, 2004, 198(3): 417～427.
[37] Tang V, Dhirapong A, Yabes A P, et al. TNF-alpha-mediated apoptosis in vascular smooth muscle cells requires p73.[J]. Am J Physiol Cell Physiol, 2005, 289(1): 199～206.
[38] 余丹青，陈纪言，周颖玲等．冠脉斑块稳定性与肿瘤坏死因子相关研究[J]．岭南心血管病杂志，2002，8(5)：332～335．
[39] Schreyer S A, Peschon J J, LeBoeuf R C. Accelerated atherosclerosis in mice lacking tumor necrosis factor receptor p55.[J]. J Biol Chem, 1996, 271(42): 26174～26178.
[40] Schreyer S A, Vick C M, LeBoeuf R C. Loss of lymphotoxin-alpha but not tumor necrosis factor-alpha reduces atherosclerosis in mice.[J]. J Biol Chem, 2002, 277(14): 12364～12368.
[41] Hansen P R, Chew M, Zhou J, et al. Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNFalpha confers no additional benefit.[J]. Atherosclerosis, 2001, 158(1): 87～94.
[42] Elhage R, Maret A, Pieraggi M T, et al. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice.[J]. Circulation, 1998, 97(3): 242～244.