MCP-1与2型糖尿病大血管病变关系的临床研究
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摘要
目的:比较糖尿病无大血管并发症和糖尿病伴大血管并发症的2型糖尿病患者血清单核细胞趋化蛋白-1(MCP-1)水平,单核细胞上MCP-1蛋白表达水平的变化,探讨MCP-1在糖尿病大血管病变发生、发展中的作用。
方法:本实验收集了正常对照组20例(A组),其中男性11例,女性9例,平均年龄为(54.30±7.39)岁;2型糖尿病无大血管病变组(B组)30例,其中男性17例,女性13例,平均年龄为(54.53±9.19)岁,病程(4.50±3.50)年;2型糖尿病有大血管病变组(C组)22例,其中男性12例,女性10例,平均年龄为(56.45±7.30岁),病程(6.21±3.88)年。用流式细胞仪检测单核细胞上MCP-1蛋白表达水平,用竞争性酶联免疫吸附法(ELISA)分析血清MCP-1水平。
结果:
(1)组间血清MCP-1水平比较:与正常对照组【(39.14±7.43)pg/ml】比较,糖尿病不伴大血管病变组血清MCP-1水平【(46.18±5.84)pg/ml】显著增高(p<0.01),伴大血管病变者【(54.36±9.58)pg/ml】进一步显著升高(p<0.01);与不伴大血管病变者比较,伴大血管病变者血清MCP-1水平显著增高(p<0.01)。
(2)组间单核细胞上MCP-1表达水平比较:与正常对照组【(0.28±0.09)%】比较,糖尿病无大血管病变组单核细胞上MCP-1蛋白表达水平【(0.70±0.36)%】显著增高(p<0.01),伴大血管病变者【(1.02±0.33)%】进一步明显升高(p<0.01);与不伴大血管病变者比较,伴大血管病变者单核细胞上MCP-1水平明显升高(p<0.01)。
(3)相关性分析:直线相关分析显示血清MCP-1水平和单核细胞上MCP-1蛋白表达水平呈显著正相关(r=0.83,p<0.01);血清MCP-1水平与空腹血糖(FBG)、糖化血红蛋白(HbA1c)和HOMA-IR指数呈显著正相关(r,p分别为0.5,p<0.01; 0.29,p<0.05;0.61,p<0.01);单核细胞上MCP-1蛋白表达水平与FBG、HbA1c和HOMA-IR指数呈显著正相关(r,p分别为0.67,p<0.01;0.38, p<0.01;0.76,p<0.01)。
结论: 2型糖尿病患者体内MCP-1表达增强并参与了大血管病变的发生和发展。
目的:比较短期胰岛素强化治疗前后糖尿病患者外周血单核细胞上单核细胞趋化蛋白-1(MCP-1)表达和血清MCP-1水平的变化,探讨胰岛素治疗的抗炎作用和对大血管的保护作用及其机制。
方法:初发2型糖尿病人20例,男性14例,女性6例,平均年龄为(51.25±5.71)岁,空腹血糖(FBG)为(11.18±1.73)mmol/L,餐后血糖(P2hBG)为(17.92±2.08)mmol/L,给予胰岛素强化治疗2周,根据血糖水平调整胰岛素用量,将空腹及睡前血糖控制在3.9～8.3mmol/L,三餐2h后血糖<10mmol/L,血糖达标时间为(3.40±1.76)d。强化治疗前和治疗后分别测FBG、P2hBG、血白细胞计数(WBC),中性粒细胞百分比(N%),用流式细胞仪测胰岛素强化治疗前后单核细胞上MCP-1的表达,用竞争性酶联免疫吸附法(ELISA)测定胰岛素强化治疗前后血清MCP-1水平。选择同期参加门诊体检的正常对照者20例,男11例,女9例,平均年龄(54.30±7.39)岁。
结果
(1)与正常对照组比较,糖尿病组血清中MCP-1水平【(39.14±7.43)pg/ml VS (49.53±3.47)pg/ml】和单核细胞上MCP-1表达【(0.28±0.09)% VS(0.89±0.26)%】均显著增高(p<0.01)。
(2)与胰岛素强化治疗前比较,胰岛素强化治疗2周后,①FBG、P2hBG【治疗前分别为(11.18±1.73)和(17.92±2.08)mmol/L;治疗后分别为(6.37±1.07)和(8.27±2.12)mmol/L】显著下降(p<0.01);②WBC、N%【治疗前分别为(7.39±1.56)×109/L和(64.61±5.45)%;治疗后分别为(5.52±1.12)×109/L和(56.23±4.71)%】明显降低(p<0.01);③单核细胞上MCP-1的表达和血清中MCP-1水平【治疗前分别为(0.89±0.26)%和(49.53±3.47)pg/ml;治疗后分别为(0.50±0.18)%和(44.53±3.97)pg/ml】明显降低(p<0.01)。
(3)相关性分析:直线相关分析显示糖尿病患者单核细胞上MCP-1的表达和血清中MCP-1水平呈显著正相关(r=0.47,p<0.01);强化治疗后血清MCP-1水平降低与FBG的降低呈正相关(r=0.58,p<0.01)、与P2hBG的降低无相关性(r=0.08,p﹥0.05),与LgHOMA-IR的下降亦无相关性(r=0.39,p﹥0.05)。强化治疗后单核细胞MCP-1表达水平降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.03,0.27,0.10, p﹥0.05)。
结论:胰岛素除降糖作用外,可降低体内MCP-1表达,提示胰岛素治疗尚可通过抑制某些炎症因子的表达发挥其抗动脉粥样硬化的作用。
Objective To investigate the relationship between monocyte chemoattractant protein-1(MCP-1) and macroangiopathy in type 2 diabetics, we compared the serum MCP-1 levels and expression of MCP-1 on monocyte membrane of diabetics with or without macroangiopathy.
Methods Total 20 normal controls(group A, 45%women, mean age, 54.30±7.39years) and 30 diabetic patients without macroangiopathy (group B, 43%women, mean age, 54.53±9.19years, course, 4.50±3.50years) and 22 diabetic patients with(group C, 45%women, mean age, 56.45±7.30years, course, 6.21±3.88years) macroangiopathy were recruited. Expression of MCP-1 on monocyte membrane was measured by flow cytometry, serum MCP-1 levels were measured by enzyme linked immunosorbent assay(ELISA).
Results 1.Serum MCP-1 levels among groups: Compared with the control group【(39.14±7.43)pg/ml】, the serum MCP-1 levels in diabetics without macroangiopathy【(46.18±5.84)pg/ml】increased significantly (p<0.01), serum MCP-1 levels in diabetics with macroangiopathy【(54.36±9.58)pg/ml】increased further; compared with the diabetics without macroangiopathy group, serum MCP-1 levels in diabetics with macroangiopathy were increased significantly (p<0.01).
2.The expression of MCP-1 on monocyte membrane amnong groups: Compared with the control group【(0.28±0.09)%】, the expression of MCP-1 on monocyte membrane in diabetics without macroangiopathy【( 0.70±0.36 ) %】were significantly higher(p<0.01), the expression of MCP-1 on monocyte membrane in diabetics with macroangiopathy【(1.02±0.33)%】increased further; compared with the diabetics without macroangiopathy group, the expression of MCP-1 on monocyte membrane in diabetics with macroangiopathy increased significantly higher(p<0.01).
3.Correlation analysis: Linear correlation analysis showed that serum MCP-1 levels had positive relationship with the expression of MCP-1 on monocyte membrane in diabetics(r=0.83, p<0.01); the serum MCP-1 levels had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.5, p<0.01; r=0.29, p<0.05; r=0.61, p<0.01); the expression of MCP-1 on monocyte membrane had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.67, p<0.01; r=0.38, p<0.01; r=0.76, p<0.01).
Conclusions Type 2 diabetics in vivo had the enhanced expression of MCP-1, which might take part in the development and progression of macroangiopathy.
Objective To observe the effect of short-term insulin intensive treatment on the monocyte chemoattractant protein-1(MCP-1) expression on the monocyte surface and serum MCP-1 levels in newly-diagnosed type 2 diabetic patients, and probe its effect of anti-inflammation.
Methods 20 newly-diagnosed type 2 diabetic patients were treated by insulin intensive treatment for 2 weeks, the MCP-1 expression on the monocyte surface(by flow cytometry), serum MCP-1 levels(by enzyme linked immunosorbent assay, ELISA), fasting blood glucose(FBG), postprandial blood glucose(P2hBG), white blood cell count(WBC) and the neutrocyte percents(N%) were measured pre-treatment and post- treatment. The other 20 healthy volunteers (45%women; mean age, 54.30±7.39years) served as control subjects.
Results 1.Compared with the control group, MCP-1 expression on monocyte surface and serum MCP-1 levels of patients with type 2 diabetes increased significantly,which were (0.89±0.26)% VS (0.28±0.09%)(p<0.01) and (49.53±3.47pg/ml) VS (39.14±7.43pg/ml)(p<0.01).
2.Compared with pre-treatment, after 2 weeks of insulin intensive treatment, 1) FBG and P2hBG were significantly decreased, which were (11.18±1.73)mmol/L VS (6.37±1.07)mmol/L and (17.92±2.08)mmol/L VS (8.27±2.12)mmol/L, p<0.01; 2) WBC and N% after treatment were much lower than those of pre-treatment, which were (7.39±1.56)×109/L VS (5.52±1.12)×109/L and (64.61±5.45)% VS (56.23±4.71)%, p<0.01; 3) The MCP-1 expression on the monocyte surface and serum MCP-1 levels decreased significantly compared with pre-treatment, which were (0.50±0.18)% VS(0.89±0.26)% and (44.53±3.97)pg/ml VS(49.53±3.47)pg/ml, respectively, (p<0.01).
3.Correlation analysis: Linear correlation analysis showed that the MCP-1 expression on monocyte surface had significant and positive relationship with serum MCP-1 levels in patients with type2 diabetes(r=0.47, p<0.01); after 2 weeks of insulin treatment, the descent of serum MCP-1 levels had positive relationship with the descent of FBG(r=0.58, p<0.01), had no relationship with the descent of P2hBG(r=0.08,p>0.05) and LgHOMA-IR(r=0.39, p>0.05); after 2 weeks of insulin treatment, the descent of MCP-1 expression on monocyte membrane had no relationship with the descent of FBG(r=0.033, p>0.05), P2hBG(r=0.27, p>0.05) and LgHOMA-IR(r=0.10, p>0.05).
Conclusions Short-term insulin intensive therapy has the effect of alleviating inflammation reaction in type 2 diabetics.
方法:本实验收集了正常对照组20例(A组),其中男性11例,女性9例,平均年龄为(54.30±7.39)岁;2型糖尿病无大血管病变组(B组)30例,其中男性17例,女性13例,平均年龄为(54.53±9.19)岁,病程(4.50±3.50)年;2型糖尿病有大血管病变组(C组)22例,其中男性12例,女性10例,平均年龄为(56.45±7.30岁),病程(6.21±3.88)年。用流式细胞仪检测单核细胞上MCP-1蛋白表达水平,用竞争性酶联免疫吸附法(ELISA)分析血清MCP-1水平。
结果:
(1)组间血清MCP-1水平比较:与正常对照组【(39.14±7.43)pg/ml】比较,糖尿病不伴大血管病变组血清MCP-1水平【(46.18±5.84)pg/ml】显著增高(p<0.01),伴大血管病变者【(54.36±9.58)pg/ml】进一步显著升高(p<0.01);与不伴大血管病变者比较,伴大血管病变者血清MCP-1水平显著增高(p<0.01)。
(2)组间单核细胞上MCP-1表达水平比较:与正常对照组【(0.28±0.09)%】比较,糖尿病无大血管病变组单核细胞上MCP-1蛋白表达水平【(0.70±0.36)%】显著增高(p<0.01),伴大血管病变者【(1.02±0.33)%】进一步明显升高(p<0.01);与不伴大血管病变者比较,伴大血管病变者单核细胞上MCP-1水平明显升高(p<0.01)。
(3)相关性分析:直线相关分析显示血清MCP-1水平和单核细胞上MCP-1蛋白表达水平呈显著正相关(r=0.83,p<0.01);血清MCP-1水平与空腹血糖(FBG)、糖化血红蛋白(HbA1c)和HOMA-IR指数呈显著正相关(r,p分别为0.5,p<0.01; 0.29,p<0.05;0.61,p<0.01);单核细胞上MCP-1蛋白表达水平与FBG、HbA1c和HOMA-IR指数呈显著正相关(r,p分别为0.67,p<0.01;0.38, p<0.01;0.76,p<0.01)。
结论: 2型糖尿病患者体内MCP-1表达增强并参与了大血管病变的发生和发展。
目的:比较短期胰岛素强化治疗前后糖尿病患者外周血单核细胞上单核细胞趋化蛋白-1(MCP-1)表达和血清MCP-1水平的变化,探讨胰岛素治疗的抗炎作用和对大血管的保护作用及其机制。
方法:初发2型糖尿病人20例,男性14例,女性6例,平均年龄为(51.25±5.71)岁,空腹血糖(FBG)为(11.18±1.73)mmol/L,餐后血糖(P2hBG)为(17.92±2.08)mmol/L,给予胰岛素强化治疗2周,根据血糖水平调整胰岛素用量,将空腹及睡前血糖控制在3.9～8.3mmol/L,三餐2h后血糖<10mmol/L,血糖达标时间为(3.40±1.76)d。强化治疗前和治疗后分别测FBG、P2hBG、血白细胞计数(WBC),中性粒细胞百分比(N%),用流式细胞仪测胰岛素强化治疗前后单核细胞上MCP-1的表达,用竞争性酶联免疫吸附法(ELISA)测定胰岛素强化治疗前后血清MCP-1水平。选择同期参加门诊体检的正常对照者20例,男11例,女9例,平均年龄(54.30±7.39)岁。
结果
(1)与正常对照组比较,糖尿病组血清中MCP-1水平【(39.14±7.43)pg/ml VS (49.53±3.47)pg/ml】和单核细胞上MCP-1表达【(0.28±0.09)% VS(0.89±0.26)%】均显著增高(p<0.01)。
(2)与胰岛素强化治疗前比较,胰岛素强化治疗2周后,①FBG、P2hBG【治疗前分别为(11.18±1.73)和(17.92±2.08)mmol/L;治疗后分别为(6.37±1.07)和(8.27±2.12)mmol/L】显著下降(p<0.01);②WBC、N%【治疗前分别为(7.39±1.56)×109/L和(64.61±5.45)%;治疗后分别为(5.52±1.12)×109/L和(56.23±4.71)%】明显降低(p<0.01);③单核细胞上MCP-1的表达和血清中MCP-1水平【治疗前分别为(0.89±0.26)%和(49.53±3.47)pg/ml;治疗后分别为(0.50±0.18)%和(44.53±3.97)pg/ml】明显降低(p<0.01)。
(3)相关性分析:直线相关分析显示糖尿病患者单核细胞上MCP-1的表达和血清中MCP-1水平呈显著正相关(r=0.47,p<0.01);强化治疗后血清MCP-1水平降低与FBG的降低呈正相关(r=0.58,p<0.01)、与P2hBG的降低无相关性(r=0.08,p﹥0.05),与LgHOMA-IR的下降亦无相关性(r=0.39,p﹥0.05)。强化治疗后单核细胞MCP-1表达水平降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.03,0.27,0.10, p﹥0.05)。
结论:胰岛素除降糖作用外,可降低体内MCP-1表达,提示胰岛素治疗尚可通过抑制某些炎症因子的表达发挥其抗动脉粥样硬化的作用。
Objective To investigate the relationship between monocyte chemoattractant protein-1(MCP-1) and macroangiopathy in type 2 diabetics, we compared the serum MCP-1 levels and expression of MCP-1 on monocyte membrane of diabetics with or without macroangiopathy.
Methods Total 20 normal controls(group A, 45%women, mean age, 54.30±7.39years) and 30 diabetic patients without macroangiopathy (group B, 43%women, mean age, 54.53±9.19years, course, 4.50±3.50years) and 22 diabetic patients with(group C, 45%women, mean age, 56.45±7.30years, course, 6.21±3.88years) macroangiopathy were recruited. Expression of MCP-1 on monocyte membrane was measured by flow cytometry, serum MCP-1 levels were measured by enzyme linked immunosorbent assay(ELISA).
Results 1.Serum MCP-1 levels among groups: Compared with the control group【(39.14±7.43)pg/ml】, the serum MCP-1 levels in diabetics without macroangiopathy【(46.18±5.84)pg/ml】increased significantly (p<0.01), serum MCP-1 levels in diabetics with macroangiopathy【(54.36±9.58)pg/ml】increased further; compared with the diabetics without macroangiopathy group, serum MCP-1 levels in diabetics with macroangiopathy were increased significantly (p<0.01).
2.The expression of MCP-1 on monocyte membrane amnong groups: Compared with the control group【(0.28±0.09)%】, the expression of MCP-1 on monocyte membrane in diabetics without macroangiopathy【( 0.70±0.36 ) %】were significantly higher(p<0.01), the expression of MCP-1 on monocyte membrane in diabetics with macroangiopathy【(1.02±0.33)%】increased further; compared with the diabetics without macroangiopathy group, the expression of MCP-1 on monocyte membrane in diabetics with macroangiopathy increased significantly higher(p<0.01).
3.Correlation analysis: Linear correlation analysis showed that serum MCP-1 levels had positive relationship with the expression of MCP-1 on monocyte membrane in diabetics(r=0.83, p<0.01); the serum MCP-1 levels had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.5, p<0.01; r=0.29, p<0.05; r=0.61, p<0.01); the expression of MCP-1 on monocyte membrane had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.67, p<0.01; r=0.38, p<0.01; r=0.76, p<0.01).
Conclusions Type 2 diabetics in vivo had the enhanced expression of MCP-1, which might take part in the development and progression of macroangiopathy.
Objective To observe the effect of short-term insulin intensive treatment on the monocyte chemoattractant protein-1(MCP-1) expression on the monocyte surface and serum MCP-1 levels in newly-diagnosed type 2 diabetic patients, and probe its effect of anti-inflammation.
Methods 20 newly-diagnosed type 2 diabetic patients were treated by insulin intensive treatment for 2 weeks, the MCP-1 expression on the monocyte surface(by flow cytometry), serum MCP-1 levels(by enzyme linked immunosorbent assay, ELISA), fasting blood glucose(FBG), postprandial blood glucose(P2hBG), white blood cell count(WBC) and the neutrocyte percents(N%) were measured pre-treatment and post- treatment. The other 20 healthy volunteers (45%women; mean age, 54.30±7.39years) served as control subjects.
Results 1.Compared with the control group, MCP-1 expression on monocyte surface and serum MCP-1 levels of patients with type 2 diabetes increased significantly,which were (0.89±0.26)% VS (0.28±0.09%)(p<0.01) and (49.53±3.47pg/ml) VS (39.14±7.43pg/ml)(p<0.01).
2.Compared with pre-treatment, after 2 weeks of insulin intensive treatment, 1) FBG and P2hBG were significantly decreased, which were (11.18±1.73)mmol/L VS (6.37±1.07)mmol/L and (17.92±2.08)mmol/L VS (8.27±2.12)mmol/L, p<0.01; 2) WBC and N% after treatment were much lower than those of pre-treatment, which were (7.39±1.56)×109/L VS (5.52±1.12)×109/L and (64.61±5.45)% VS (56.23±4.71)%, p<0.01; 3) The MCP-1 expression on the monocyte surface and serum MCP-1 levels decreased significantly compared with pre-treatment, which were (0.50±0.18)% VS(0.89±0.26)% and (44.53±3.97)pg/ml VS(49.53±3.47)pg/ml, respectively, (p<0.01).
3.Correlation analysis: Linear correlation analysis showed that the MCP-1 expression on monocyte surface had significant and positive relationship with serum MCP-1 levels in patients with type2 diabetes(r=0.47, p<0.01); after 2 weeks of insulin treatment, the descent of serum MCP-1 levels had positive relationship with the descent of FBG(r=0.58, p<0.01), had no relationship with the descent of P2hBG(r=0.08,p>0.05) and LgHOMA-IR(r=0.39, p>0.05); after 2 weeks of insulin treatment, the descent of MCP-1 expression on monocyte membrane had no relationship with the descent of FBG(r=0.033, p>0.05), P2hBG(r=0.27, p>0.05) and LgHOMA-IR(r=0.10, p>0.05).
Conclusions Short-term insulin intensive therapy has the effect of alleviating inflammation reaction in type 2 diabetics.
引文
1石巧荣,田进文,王丽英. 2型糖尿病与炎症及抗炎治疗进展.实用医学杂志, 2007, 23(15): 2289-2291.
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4 James AL, David AM, Marc SS, et al. Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes. Circulation, 2003, 107: 690~695.
5 Chacon MR, Fernandez-Real JM, Richart C, et al. Monocyte Chemoattractant Protein-1 in Obesity and Type 2 Diabetes. Insulin Sensitivity Study. Obesity, 2007, 15(3): 664-672.
6 Mine M, Okada Y, Tanikawa T, et al. Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus. Biochem Biophys Res Commun, 2006, 344(3): 780-785.
7 Simeoni E, Hoffmann MM, Winkelmann BR, et al. Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and type 2 diabetes mellitus. Diabetologia, 2004, 47(9): 1574-1580.
8 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells. Kidney Int, 2001, 60(1): 55-64.
9 Ehlermann P, Eggers K, Bierhaus A, et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6): 1-9.
10 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediated vascular inflammation and remodeling. J Clin Invest, 2005, 115(9): 2508-2516.
11 Libby P, Sukhova G, Lee RT, et al. Cytokines regulate vascular functions related to stability of the atherosclerotic plaquel. J Cardiovasc Pharmacol, 1995, 25 Suppl 2: S9-12.
12董波,黄定九,李惠丽,等.血管紧张素Ⅱ对单核细胞趋化蛋白及基因调节的意义.免疫学杂志,2002,18(3):278-280.
13王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白和极低密度脂蛋白对单核细胞MCP-1表达的影响.中华病理学杂志,1996,25(4):220-223.
14王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白对单核细胞趋化蛋白-1mRNA表达的影响.中国病理生理杂志,1997,13(2):114-117.
15王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响.中华医学杂志,1997,77(3):212-215.
16 Takaishi H, Taniguchi T, Takahashi A, et al. High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem Biophys Res Commun, 2003, 305(1): 122-128.
17 Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl A cad Sci U S A, 2003, 100(12): 7265-7270.
1 Gerhardt CC, Romero IA, Cancello R, et al. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol CellEndocrinol, 2001, 175(1-2): 81-92.
2 Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl A cad Sci U S A, 2003, 100(12): 7265-7270.
3 Piemonti L, Eugenio B, Nano R, et al. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Dia-betes,2002,51:55-65.
4 Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med, 1999, 340(2): 115-126.
5刘丽军,王守力,韩雅玲.单核细胞趋化因子-1/白细胞介素-6在动脉粥洋硬化发展中的作用.西南军医, 2007, 9(1): 80-82.
6 Donath MY, Ehses JA, Maedler K, et al. Mechanisms of beta-cell death in type 2 diabetes. 2005, 54 Suppl 2:S108-113.
7 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells. Kidney Int, 2001, 60(1):55-64.
8 Ehlermann P, Eggers K, Bierhaus A, et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6):1-9.
9 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediated vascular inflammation and remodeling. J Clin Invest, 2005, 115(9):2508-2516.
10 Libby P, Sukhova G, Lee RT, et al. Cytokines regulate vascular functions related to stability of the atherosclerotic plaquel. J Cardiovasc. Pharmacol, 1995, 25(12):9-12.
11 Kamei N, Tobe K, Suzuki R, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem, 2006, 281(36):26602-26614.
12 Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness. J Clin Invest, 2005, 115(8):2069-2072.
13 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005, 115:2277-2286.
14 Aljada A, Ghaninm H, Saadeh R, et al. Insulin inhibits NF kappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab, 2001, 86(1):450-453.
15 Dandona P,Aljada A,Mohanty P,et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB inmononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab,2001,86(7):3257-3265.
16 AljadaA, Saadeh R, Assian E, et al. Insulin inhibits the expression of intercellular adhesionmolecule-1 by human aortic endothelial cells through stimulation ofnitric oxide. JClin Endocrinol Metab, 2000, 85(7): 2572 -2575.
17 Jeschke MG, Einspanier R, Klein D, et al. Insulin attenuates the systemic inflammatory response to thermal trauma. Mol Med, 2002,8(8):443-450.
18 Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness. J Clin Invest, 2005, 115(8): 2069–2072.
19朱本章,马卫国,南佳彦.胰岛素抗炎的作用及研究进展.中国实用内科杂志, 2006, 26(17):1309-1311.
20 Jeschke MG, Klein D, Bolder U, et al. Insulin attenuates the systemic inflammatory response in endotoxemic rats. Endocrinology, 2004, 145(9):4084–4093.
21姚咏明,孟海东.脓毒症高血糖与胰岛素强化治疗策略.中国危重病急救医学2006, 18(2): 68-70.
22 Das UN. Insulin and the critically ill. Crit Care, 2002, 6(3): 262–263.
23李艳波,邓华聪,郑丹等. P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响.中华糖尿病杂志, 2004, 12(4):287-289.
24 Wright E, Scism-Bacon JL, Glass LC, et al. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract, 2006, 60(3):308-314.
25 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005,115(8): 2277–2286.
26 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005, 115(8): 2277-2286.
27 Festa AD,Agostino RD,Howard G,et al.Chronic subclinical inflammation as part of the insulin resistance syndrome. Circultion, 2000,102(1):42~47.
28 Mosmann TR, Coffman RL. Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol,1989; 7: 145-173.
29 Mosmann TR, Sad S. The expanding universe of T-cell subets: Th1, Th2 and more. Immunol Today, 1996; 17(3): 138-146.
30 Viardot A, Grey ST, Mackay F, et al. Potential Antiinflammatory role of insulin via the preferential polarization of effector T Cells toward a T Helper 2 Phenotype. Endocrinology, 2007, 148(1):346-353.
1 Weisberg SP, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metaboliceffects of high-fat feeding. J. Clin. Invest, 2006, 116(1):115-124.
2 Veillard NR, Steffens S, Pelli G, et al. Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo. Circulation, 2005, 112(6):870-878.
3 Shi Q, Vandeberg JF, Jett C, et al. Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet. Am J Clin Nutr, 2005, 82(4):751-759.
4 Lee PC, Ho IC, Lee TC. Oxidative stress mediates sodium Arsenite-induced expression of Heme oxygenase-1,monocyte chemoattractant protein-1,and interleukin-6 in vascular smooth muscle cells. Toxicological sciences, 2005, 85(1):541-550.
5 Viedt C, Vogel J, Athanasiou T, et al. Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-[kappa] B and activator protein-1. Arterioscler thromb vasc biol, 2002, 22(6):914-920.
6 Jager A, Victor W, Hinsbergh V, et al. Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes. Diabetes, 2000, 49(3):485-491.
7 Waleh N, Seidner S, Mccurnin D, et al. The role of monocyte-derived cells and inflammation in baboon ductus arteriosus remodeling.Pediatric research, 2005, 57(2):254-262.
8李艳波,邓华聪,郑丹等.P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响.中华糖尿病杂志,2004,12(4):287-289.
9 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells .Kidney Int,2001,60(1):55-64.
10 Ehlermann P,Eggers K,Bierhaus A,et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6):1-9.
11 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediatedvascular inflammation and remodeling. J Clin Invest, 2005, 115(9):2508-2516.
12 Dandona P,Mohanty P,Chaudhuri A,et al.Insulin infusion in acute illness.J Clin invest,2005,115(8):2069-2072.
13 Langouche L,Vanhorebeek I,Vlasselaers D,et al.Intensive insulin the rapy protects the endothelium of critically ill patients.J Clin Invest,2005,115(8):2277-2286.
14 Aljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF kappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab, 2001, 86(1): 450-453.
15 Di Gregorio, Yao-Borengasser A, Rasouli N, et al. Expression of CD68 and macrophage chemoattractant protein -1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes,2005,54(8):2305-2313.
16 Hattori Y, Suzuki K, Hattori S, et al. Metformin inhibits cytokine-induced nuclear factorкB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 2006, 47(6):1183-1188.
17 Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor-кB in human vascular wall cells. Arterioscler thromb vasc boil, 2006,26(3):611-617.
18 Wake R, Kim-Mitsuyama S, Izumi Y, et al. Beneficial effect of candesartan on rat diastolic heart failure. Journal of Pharmacological sciences,2005, 98(4):372-379.
19 Martin-ventura JL, Blanco-colio LM, Gomez-hernandez A, et al. Intensive treatment with atorvastantin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month.Stroke, 2005, 36(8):1796-1800.
20 Shokawa T, Yoshizumi M, Yamamoto H, et al. Induction of heme oxygenase-1 inhibits monocyte chemoattractant protein-1 mRNA expression in U937 cells. Journal of Pharmacological sciences, 2006, 100(2):162-166.
2 Chazova TE, Masenko VP, Zykov KA, et al. The role of inflammation factors in development of acute coronary syndrome in patientswith type 2 diabetes mellitus and impaired glucose tolerance. TerArkh, 2007, 79: 60-64.
3 Werle M, SclmaL U, Hanna K. MCP-l induces activation of MAP kinases ERK, JNK and p38 MAPK in human endothelial cells. Cardiovasc Res, 2002, 56(2): 284~292.
4 James AL, David AM, Marc SS, et al. Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes. Circulation, 2003, 107: 690~695.
5 Chacon MR, Fernandez-Real JM, Richart C, et al. Monocyte Chemoattractant Protein-1 in Obesity and Type 2 Diabetes. Insulin Sensitivity Study. Obesity, 2007, 15(3): 664-672.
6 Mine M, Okada Y, Tanikawa T, et al. Increased expression levels of monocyte CCR2 and monocyte chemoattractant protein-1 in patients with diabetes mellitus. Biochem Biophys Res Commun, 2006, 344(3): 780-785.
7 Simeoni E, Hoffmann MM, Winkelmann BR, et al. Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and type 2 diabetes mellitus. Diabetologia, 2004, 47(9): 1574-1580.
8 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells. Kidney Int, 2001, 60(1): 55-64.
9 Ehlermann P, Eggers K, Bierhaus A, et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6): 1-9.
10 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediated vascular inflammation and remodeling. J Clin Invest, 2005, 115(9): 2508-2516.
11 Libby P, Sukhova G, Lee RT, et al. Cytokines regulate vascular functions related to stability of the atherosclerotic plaquel. J Cardiovasc Pharmacol, 1995, 25 Suppl 2: S9-12.
12董波,黄定九,李惠丽,等.血管紧张素Ⅱ对单核细胞趋化蛋白及基因调节的意义.免疫学杂志,2002,18(3):278-280.
13王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白和极低密度脂蛋白对单核细胞MCP-1表达的影响.中华病理学杂志,1996,25(4):220-223.
14王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白对单核细胞趋化蛋白-1mRNA表达的影响.中国病理生理杂志,1997,13(2):114-117.
15王国平,邓仲端,翟志玲.氧化修饰的极低密度脂蛋白和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响.中华医学杂志,1997,77(3):212-215.
16 Takaishi H, Taniguchi T, Takahashi A, et al. High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochem Biophys Res Commun, 2003, 305(1): 122-128.
17 Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl A cad Sci U S A, 2003, 100(12): 7265-7270.
1 Gerhardt CC, Romero IA, Cancello R, et al. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol CellEndocrinol, 2001, 175(1-2): 81-92.
2 Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl A cad Sci U S A, 2003, 100(12): 7265-7270.
3 Piemonti L, Eugenio B, Nano R, et al. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Dia-betes,2002,51:55-65.
4 Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med, 1999, 340(2): 115-126.
5刘丽军,王守力,韩雅玲.单核细胞趋化因子-1/白细胞介素-6在动脉粥洋硬化发展中的作用.西南军医, 2007, 9(1): 80-82.
6 Donath MY, Ehses JA, Maedler K, et al. Mechanisms of beta-cell death in type 2 diabetes. 2005, 54 Suppl 2:S108-113.
7 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells. Kidney Int, 2001, 60(1):55-64.
8 Ehlermann P, Eggers K, Bierhaus A, et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6):1-9.
9 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediated vascular inflammation and remodeling. J Clin Invest, 2005, 115(9):2508-2516.
10 Libby P, Sukhova G, Lee RT, et al. Cytokines regulate vascular functions related to stability of the atherosclerotic plaquel. J Cardiovasc. Pharmacol, 1995, 25(12):9-12.
11 Kamei N, Tobe K, Suzuki R, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem, 2006, 281(36):26602-26614.
12 Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness. J Clin Invest, 2005, 115(8):2069-2072.
13 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005, 115:2277-2286.
14 Aljada A, Ghaninm H, Saadeh R, et al. Insulin inhibits NF kappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab, 2001, 86(1):450-453.
15 Dandona P,Aljada A,Mohanty P,et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB inmononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab,2001,86(7):3257-3265.
16 AljadaA, Saadeh R, Assian E, et al. Insulin inhibits the expression of intercellular adhesionmolecule-1 by human aortic endothelial cells through stimulation ofnitric oxide. JClin Endocrinol Metab, 2000, 85(7): 2572 -2575.
17 Jeschke MG, Einspanier R, Klein D, et al. Insulin attenuates the systemic inflammatory response to thermal trauma. Mol Med, 2002,8(8):443-450.
18 Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness. J Clin Invest, 2005, 115(8): 2069–2072.
19朱本章,马卫国,南佳彦.胰岛素抗炎的作用及研究进展.中国实用内科杂志, 2006, 26(17):1309-1311.
20 Jeschke MG, Klein D, Bolder U, et al. Insulin attenuates the systemic inflammatory response in endotoxemic rats. Endocrinology, 2004, 145(9):4084–4093.
21姚咏明,孟海东.脓毒症高血糖与胰岛素强化治疗策略.中国危重病急救医学2006, 18(2): 68-70.
22 Das UN. Insulin and the critically ill. Crit Care, 2002, 6(3): 262–263.
23李艳波,邓华聪,郑丹等. P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响.中华糖尿病杂志, 2004, 12(4):287-289.
24 Wright E, Scism-Bacon JL, Glass LC, et al. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract, 2006, 60(3):308-314.
25 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005,115(8): 2277–2286.
26 Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest, 2005, 115(8): 2277-2286.
27 Festa AD,Agostino RD,Howard G,et al.Chronic subclinical inflammation as part of the insulin resistance syndrome. Circultion, 2000,102(1):42~47.
28 Mosmann TR, Coffman RL. Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol,1989; 7: 145-173.
29 Mosmann TR, Sad S. The expanding universe of T-cell subets: Th1, Th2 and more. Immunol Today, 1996; 17(3): 138-146.
30 Viardot A, Grey ST, Mackay F, et al. Potential Antiinflammatory role of insulin via the preferential polarization of effector T Cells toward a T Helper 2 Phenotype. Endocrinology, 2007, 148(1):346-353.
1 Weisberg SP, Hunter D, Huber R, et al. CCR2 modulates inflammatory and metaboliceffects of high-fat feeding. J. Clin. Invest, 2006, 116(1):115-124.
2 Veillard NR, Steffens S, Pelli G, et al. Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo. Circulation, 2005, 112(6):870-878.
3 Shi Q, Vandeberg JF, Jett C, et al. Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet. Am J Clin Nutr, 2005, 82(4):751-759.
4 Lee PC, Ho IC, Lee TC. Oxidative stress mediates sodium Arsenite-induced expression of Heme oxygenase-1,monocyte chemoattractant protein-1,and interleukin-6 in vascular smooth muscle cells. Toxicological sciences, 2005, 85(1):541-550.
5 Viedt C, Vogel J, Athanasiou T, et al. Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in human smooth muscle cells by differential activation of nuclear factor-[kappa] B and activator protein-1. Arterioscler thromb vasc biol, 2002, 22(6):914-920.
6 Jager A, Victor W, Hinsbergh V, et al. Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes. Diabetes, 2000, 49(3):485-491.
7 Waleh N, Seidner S, Mccurnin D, et al. The role of monocyte-derived cells and inflammation in baboon ductus arteriosus remodeling.Pediatric research, 2005, 57(2):254-262.
8李艳波,邓华聪,郑丹等.P38信号通路对人脐静脉内皮细胞单核细胞趋化蛋白-1表达的影响.中华糖尿病杂志,2004,12(4):287-289.
9 Lee S, Kim B, Sik Y, et al. Hight glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells .Kidney Int,2001,60(1):55-64.
10 Ehlermann P,Eggers K,Bierhaus A,et al. Increased proinflammatoryendothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc diabetol, 2006, 5(6):1-9.
11 Zhan Y, Brown C, Maynard E, et al. Ets-1 is a critical regulator of AngⅡ-mediatedvascular inflammation and remodeling. J Clin Invest, 2005, 115(9):2508-2516.
12 Dandona P,Mohanty P,Chaudhuri A,et al.Insulin infusion in acute illness.J Clin invest,2005,115(8):2069-2072.
13 Langouche L,Vanhorebeek I,Vlasselaers D,et al.Intensive insulin the rapy protects the endothelium of critically ill patients.J Clin Invest,2005,115(8):2277-2286.
14 Aljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF kappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab, 2001, 86(1): 450-453.
15 Di Gregorio, Yao-Borengasser A, Rasouli N, et al. Expression of CD68 and macrophage chemoattractant protein -1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes,2005,54(8):2305-2313.
16 Hattori Y, Suzuki K, Hattori S, et al. Metformin inhibits cytokine-induced nuclear factorкB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 2006, 47(6):1183-1188.
17 Isoda K, Young JL, Zirlik A, et al. Metformin inhibits proinflammatory responses and nuclear factor-кB in human vascular wall cells. Arterioscler thromb vasc boil, 2006,26(3):611-617.
18 Wake R, Kim-Mitsuyama S, Izumi Y, et al. Beneficial effect of candesartan on rat diastolic heart failure. Journal of Pharmacological sciences,2005, 98(4):372-379.
19 Martin-ventura JL, Blanco-colio LM, Gomez-hernandez A, et al. Intensive treatment with atorvastantin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month.Stroke, 2005, 36(8):1796-1800.
20 Shokawa T, Yoshizumi M, Yamamoto H, et al. Induction of heme oxygenase-1 inhibits monocyte chemoattractant protein-1 mRNA expression in U937 cells. Journal of Pharmacological sciences, 2006, 100(2):162-166.