核因子-κB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:通过比较糖尿病有大血管病变病人和糖尿病无大血管病变病人的外周血单核细胞中核因子κB (NF-κB)的表达水平,来探讨NF-κB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。留取清晨空腹肘静脉血5ml,分离出单核细胞,采用酶联免疫吸附法、流式细胞仪计数法检测单核细胞中NF-κB表达水平。
结果:
1.组间流式细胞仪测得NF-κB表达水平比较:与正常对照组【(3.667±0.376)%】比较,糖尿病无大血管病变组单核细胞中NF-κB表达水平【(10.198±0.467)%】显著增高,伴大血管病变者进一步明显升高【(15.270±0.820)%】,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中NF-κB水平明显升高,p<0.01。
2.组间ELISA法测得NF-κB表达水平比较:与正常对照组【(263.695±45.746)pg/ml】比较,糖尿病不伴大血管病变组NF-κB水平【(362.777±27.900)pg/ml】显著增高,伴大血管病变者进一步显著升高【(450.800±24.320)pg/ml】,p<0.01;与不伴大血管病变者比较,伴大血管病变者NF-κB水平显著增高,(p<0.01)。
3.相关性分析:直线相关分析显示流式细胞仪和ELISA法检测单核细胞中NF-κB的表达水平呈显著正相关(r=0.793,p<0.01);在糖尿病无大血管病变和糖尿病合并大血管病变2组中,流式细胞仪检测法测得的NF-κB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0.736, p<0.01; 0.827, p<0.01; 0.843, p<0.01); ELISA法测得的NF-κB与与FBG、HbA1c和HOMA-IR指数呈显著正相关(r, p分别为0.526, p<0.01; 0.531, p<0.01; 0.76, p<0.01)。
结论:糖尿病患者外周血单核细胞中核因子NF-KB表达的增加,并参与了糖尿病并大血管病变的发生发展过程。
目的:通过比较短期胰岛素强化治疗前后的初发2型糖尿病病人外周血单核细胞中核因子-κB (NF-κB)的表达水平的变化,来探讨胰岛素的抗炎作用和对大血管的保护作用的机制。
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%)和空腹胰岛素,治疗前后留取清晨空腹肘静脉血5ml,分离出单核细胞,采用酶联免疫吸附法(ELISA)、流式细胞仪计数法(FCM)检测血单核细胞中NF-κB表达水平,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与正常对照组比较用ELISA法检测的糖尿病组单核细胞中NF-κB蛋白表达水平【(352.11±20.04)pg/mlVS(263.70±45.75)pg/ml】和用FCM法检测的糖尿病组单核细胞中NF-κB蛋白表达水平【(15.53±2.49)%VS(3.67±1.68)%】比较显著增高,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用FCM法和ELISA法检测的单核细胞中NF-κB蛋白表达水平【治疗前分别为(15.53±2.49)%和(352.11±20.04)pg/ml;治疗后分别为(12.22±2.80)%和(331.75±19.20)pg/ml】明显降低,p<0.01。
3相关性分析采用流式细胞仪和ELASA两种方法测定的单核细胞内NF-κB蛋白表达水平呈显著正相关(r=0.642,p<0.01);强化治疗后FCM法检测的单核细胞中NF-κB水平降低与FBG的降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.02,0.10,0.23, p﹥0.05)。强化治疗后ELISA法检测NF-κB水平降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.37,0.25,0.14, p﹥0.05)。
结论: 2型糖尿病患者体内存在低度炎症,胰岛素除降糖作用外,胰岛素强化治疗可降低单核细胞NF-κB表达,减轻炎症反应进而发挥其抗动脉粥样硬化的作用。
Objective: To investigate the relationship between NF kappa-B (NF-κB) and the development of diabetic macroangiopathy in patients with type 2 diabetes, we compare the expression level of Nuclear Factor-κB in mononuclear cell of type 2 diabetes patients with and without macroangiopathy.
Methods: Total 20 normal controls(group A, 45%women, mean age, 54.30±7.39years) and 30 diabetic patients without macro-angiopathy (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) macro-angiopathy were recruited, mononuclear cell were separated from whole blood, NF kappa-B (NF-κB) expression level in mononuclear cells were detected by enzyme-linked immunosorbent assay(ELISA) and flow cytometry (FCM).
Results: 1.The expression of NF-κB detected by FCM group comparison: Compared with the control group【(3.667±0.376)%】, the expression of NF-κB in diabetics without macro-angiopathy【(10.198±0.467)%】were significantly higher(p<0.01), the expression of NF-κB in diabetics with macro-angiopathy【(15.270±0.820)%】were further higher; compared with the diabetics without macro-angiopathy group, the expression of NF-κB in diabetics with macro-angiopathy were significantly higher(p<0.01).
2.The expression of NF-κB detected by ELISA group comparison: Compared with the control group【(263.695±45.746)pg/ml】, the expression of NF-κB in diabetics without macro-angiopathy【(362.777±27.900)pg/ml】were significantly higher(p<0.01), the expression of NF-κB in diabetics with macro-angiopathy【(450.800±24.320)pg/ml】 were further higher; compared with the diabetics without macro-angiopathy group, the expression of NF-κB in diabetics with macro-angiopathy were significantly higher(p<0.01).
3.Correlation analysis: Linear correlation analysis showed that the expression level of NF-κB detected by FCM had positive relationship with the expression level of NF-κB detected by ELISA in diabetics(r=0.793, p<0.01); the expression level of NF-κB detected by FCM had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.736, p<0.01; r=0.827, p<0.01; r=0.843, p<0.01); the expression level of NF-κB detected by ELISA had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.526, p<0.01; r=0.531, p<0.01; r=0.76, p<0.01).
Conclusion: Increased level of NF-κB in peripheral blood mononuclear might be risk factor for peripheral macroangiopathy in patients with diabetes.
Objective: To investigate the anti-inflammatory effects of insulin by observing the effect of short-term intensive insulin therapy on the expression level of Nuclear Factor-κB in peripheral blood mononuclear cell of newly-diagnosed type 2 diabetics.
Method: 20 newly-diagnosed type 2 diabetic patients(30%women, mean age (51.25±5.71)years,fasting blood glucose(FBG)(11.18±1.73)mmol/L,postprandial blood glucose(P2hBG)(17.92±2.08)mmol/L) )were treated by intensive insulin therapy for 2 weeks, mononuclear cell were separated from whole blood, NF-κB expression level in mononuclear cells were detected by enzyme-linked immunosorbent assay(ELISA) and flow cytometry (FCM), FBG , P2hBG , white blood cell count(WBC), neutrocyte percents(N%) and fasting serum insulin(FINS) 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 The expression levels of Nuclear Factor-κB detected by ELISA【(352.11±20.04)pg/mlVS(263.70±45.75)pg/ml】and FCM【(15.53±2.49)%VS (3.67±1.68)%】in mononuclear cell of type 2 diabetes patients were significantly higher than those of control subjects(p<0.01).
2 After short-term intensive insulin therapy for 2 weeks,①FBG 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;②WBC and N% 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;③Compared to those of pre-treatment, the expression level of Nuclear Factor-κB detected by ELISA【(352.11±20.04)pg/ml VS (331.75±19.20)pg/ml】and FCM【(15.53±2.49)% VS (12.22±2.80)%】in mononuclear cell of type 2 diabetes patients were significantly decreased(p<0.01).
3 Correlation analysis: Linear correlation analysis showed that The expression levels of Nuclear Factor-κB detected by ELISA had significant and positive relationship with .The expression levels of Nuclear Factor-κB detected by FCM (r=0.642,p<0.01) ; after 2 weeks of insulin treatment, the descent of Nuclear Factor-κB level detected by FCM had had no relationship with the descent of FBG(r=0.02,p>0.05), P2hBG(r=0.10,p>0.05) and LgHOMA-IR(r=0.23,p>0.05); after 2 weeks of insulin treatment, the descent of Nuclear Factor-κB detected by ELISA had no relationship with the descent of FBG(r=0.37,p>0.05), P2hBG(r=0.25,p>0.05) and LgHOMA-IR(r=0.14,p>0.05).
Conclusion: There are existed low-degree of inflammation reaction in type 2 diabetics, Intensive Insulin Therapy can decrease the level of NF-κB in peripheral blood mononuclear cell and reduce the inflammatory reaction.
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。留取清晨空腹肘静脉血5ml,分离出单核细胞,采用酶联免疫吸附法、流式细胞仪计数法检测单核细胞中NF-κB表达水平。
结果:
1.组间流式细胞仪测得NF-κB表达水平比较:与正常对照组【(3.667±0.376)%】比较,糖尿病无大血管病变组单核细胞中NF-κB表达水平【(10.198±0.467)%】显著增高,伴大血管病变者进一步明显升高【(15.270±0.820)%】,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中NF-κB水平明显升高,p<0.01。
2.组间ELISA法测得NF-κB表达水平比较:与正常对照组【(263.695±45.746)pg/ml】比较,糖尿病不伴大血管病变组NF-κB水平【(362.777±27.900)pg/ml】显著增高,伴大血管病变者进一步显著升高【(450.800±24.320)pg/ml】,p<0.01;与不伴大血管病变者比较,伴大血管病变者NF-κB水平显著增高,(p<0.01)。
3.相关性分析:直线相关分析显示流式细胞仪和ELISA法检测单核细胞中NF-κB的表达水平呈显著正相关(r=0.793,p<0.01);在糖尿病无大血管病变和糖尿病合并大血管病变2组中,流式细胞仪检测法测得的NF-κB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0.736, p<0.01; 0.827, p<0.01; 0.843, p<0.01); ELISA法测得的NF-κB与与FBG、HbA1c和HOMA-IR指数呈显著正相关(r, p分别为0.526, p<0.01; 0.531, p<0.01; 0.76, p<0.01)。
结论:糖尿病患者外周血单核细胞中核因子NF-KB表达的增加,并参与了糖尿病并大血管病变的发生发展过程。
目的:通过比较短期胰岛素强化治疗前后的初发2型糖尿病病人外周血单核细胞中核因子-κB (NF-κB)的表达水平的变化,来探讨胰岛素的抗炎作用和对大血管的保护作用的机制。
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%)和空腹胰岛素,治疗前后留取清晨空腹肘静脉血5ml,分离出单核细胞,采用酶联免疫吸附法(ELISA)、流式细胞仪计数法(FCM)检测血单核细胞中NF-κB表达水平,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与正常对照组比较用ELISA法检测的糖尿病组单核细胞中NF-κB蛋白表达水平【(352.11±20.04)pg/mlVS(263.70±45.75)pg/ml】和用FCM法检测的糖尿病组单核细胞中NF-κB蛋白表达水平【(15.53±2.49)%VS(3.67±1.68)%】比较显著增高,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用FCM法和ELISA法检测的单核细胞中NF-κB蛋白表达水平【治疗前分别为(15.53±2.49)%和(352.11±20.04)pg/ml;治疗后分别为(12.22±2.80)%和(331.75±19.20)pg/ml】明显降低,p<0.01。
3相关性分析采用流式细胞仪和ELASA两种方法测定的单核细胞内NF-κB蛋白表达水平呈显著正相关(r=0.642,p<0.01);强化治疗后FCM法检测的单核细胞中NF-κB水平降低与FBG的降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.02,0.10,0.23, p﹥0.05)。强化治疗后ELISA法检测NF-κB水平降低与FBG、P2hBG和LgHOMA-IR的下降均无相关性(r分别为0.37,0.25,0.14, p﹥0.05)。
结论: 2型糖尿病患者体内存在低度炎症,胰岛素除降糖作用外,胰岛素强化治疗可降低单核细胞NF-κB表达,减轻炎症反应进而发挥其抗动脉粥样硬化的作用。
Objective: To investigate the relationship between NF kappa-B (NF-κB) and the development of diabetic macroangiopathy in patients with type 2 diabetes, we compare the expression level of Nuclear Factor-κB in mononuclear cell of type 2 diabetes patients with and without macroangiopathy.
Methods: Total 20 normal controls(group A, 45%women, mean age, 54.30±7.39years) and 30 diabetic patients without macro-angiopathy (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) macro-angiopathy were recruited, mononuclear cell were separated from whole blood, NF kappa-B (NF-κB) expression level in mononuclear cells were detected by enzyme-linked immunosorbent assay(ELISA) and flow cytometry (FCM).
Results: 1.The expression of NF-κB detected by FCM group comparison: Compared with the control group【(3.667±0.376)%】, the expression of NF-κB in diabetics without macro-angiopathy【(10.198±0.467)%】were significantly higher(p<0.01), the expression of NF-κB in diabetics with macro-angiopathy【(15.270±0.820)%】were further higher; compared with the diabetics without macro-angiopathy group, the expression of NF-κB in diabetics with macro-angiopathy were significantly higher(p<0.01).
2.The expression of NF-κB detected by ELISA group comparison: Compared with the control group【(263.695±45.746)pg/ml】, the expression of NF-κB in diabetics without macro-angiopathy【(362.777±27.900)pg/ml】were significantly higher(p<0.01), the expression of NF-κB in diabetics with macro-angiopathy【(450.800±24.320)pg/ml】 were further higher; compared with the diabetics without macro-angiopathy group, the expression of NF-κB in diabetics with macro-angiopathy were significantly higher(p<0.01).
3.Correlation analysis: Linear correlation analysis showed that the expression level of NF-κB detected by FCM had positive relationship with the expression level of NF-κB detected by ELISA in diabetics(r=0.793, p<0.01); the expression level of NF-κB detected by FCM had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.736, p<0.01; r=0.827, p<0.01; r=0.843, p<0.01); the expression level of NF-κB detected by ELISA had positive relationship with FBG, HbA1c and LgHoma-IR(r=0.526, p<0.01; r=0.531, p<0.01; r=0.76, p<0.01).
Conclusion: Increased level of NF-κB in peripheral blood mononuclear might be risk factor for peripheral macroangiopathy in patients with diabetes.
Objective: To investigate the anti-inflammatory effects of insulin by observing the effect of short-term intensive insulin therapy on the expression level of Nuclear Factor-κB in peripheral blood mononuclear cell of newly-diagnosed type 2 diabetics.
Method: 20 newly-diagnosed type 2 diabetic patients(30%women, mean age (51.25±5.71)years,fasting blood glucose(FBG)(11.18±1.73)mmol/L,postprandial blood glucose(P2hBG)(17.92±2.08)mmol/L) )were treated by intensive insulin therapy for 2 weeks, mononuclear cell were separated from whole blood, NF-κB expression level in mononuclear cells were detected by enzyme-linked immunosorbent assay(ELISA) and flow cytometry (FCM), FBG , P2hBG , white blood cell count(WBC), neutrocyte percents(N%) and fasting serum insulin(FINS) 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 The expression levels of Nuclear Factor-κB detected by ELISA【(352.11±20.04)pg/mlVS(263.70±45.75)pg/ml】and FCM【(15.53±2.49)%VS (3.67±1.68)%】in mononuclear cell of type 2 diabetes patients were significantly higher than those of control subjects(p<0.01).
2 After short-term intensive insulin therapy for 2 weeks,①FBG 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;②WBC and N% 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;③Compared to those of pre-treatment, the expression level of Nuclear Factor-κB detected by ELISA【(352.11±20.04)pg/ml VS (331.75±19.20)pg/ml】and FCM【(15.53±2.49)% VS (12.22±2.80)%】in mononuclear cell of type 2 diabetes patients were significantly decreased(p<0.01).
3 Correlation analysis: Linear correlation analysis showed that The expression levels of Nuclear Factor-κB detected by ELISA had significant and positive relationship with .The expression levels of Nuclear Factor-κB detected by FCM (r=0.642,p<0.01) ; after 2 weeks of insulin treatment, the descent of Nuclear Factor-κB level detected by FCM had had no relationship with the descent of FBG(r=0.02,p>0.05), P2hBG(r=0.10,p>0.05) and LgHOMA-IR(r=0.23,p>0.05); after 2 weeks of insulin treatment, the descent of Nuclear Factor-κB detected by ELISA had no relationship with the descent of FBG(r=0.37,p>0.05), P2hBG(r=0.25,p>0.05) and LgHOMA-IR(r=0.14,p>0.05).
Conclusion: There are existed low-degree of inflammation reaction in type 2 diabetics, Intensive Insulin Therapy can decrease the level of NF-κB in peripheral blood mononuclear cell and reduce the inflammatory reaction.
引文
1李秀钧,邬元红.糖尿病是一种炎症性疾病.中华内分泌代谢杂志,2003,19(4):251-253
2 Nitenberg A. Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment .[J]. Presse Med, 2005 ,34(21):1654-61.
3 Ho E, Bray TM . NF-κB activation and diabetogenesis. [J]. Soc Exp Biol Med, 1999,222(3):205-13.
4 De Martin R, Hoeth M , Hofer-Warbinek R, et al. The transcription factor NF-kappa B and the regulation of vascular cell function. [J]. Arterioscler Thromb Vasc Biol, 2000,20(11):E83-8.
5 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.
6 Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factorκappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis [J]. Proc Natl Acad Sci U S A,2004,101(15) :5634-9.
7 Wilson SH, Caplice NM, Simari RD, et al. Activated nuclear factor- kappaB is present in the coronary vasculature in experimental hypercholesterolemia. [J]. Atherosclerosis, 2000, 148(1):23.
8 Brasier AR. The NF-kappaB regulatory network.Cardiovasc Toxicol. 2006, 6(2):111-3
9 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
10 E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
11 Lee S, Kim B, Sik Y, et al. High glucose induces MCP-1 expression partly viatyrosine kinase-AP-1 pathway in peritoneal mesothelial cells [J]. Kidney Int,2001,60:55-64.
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 Lu C, He JC, Cai W ,et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. [J]. Proc Natl Acad Sci USA, 2004,101(32):11767-72.
14 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.
15 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
16 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
17 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
18 Silswal N, Singh AK, Aruna B,et al. Human resistin stimulates the. pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages. by NF-kappaB-dependent pathway. [J]. Biochem Biophys Res Commun, 2005, 334(4): 1092-101.
19 Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates lkappaB in mononuclear cells in obese subjects:evidence for an antiinflammatory effect? [J]. Clin Endocrinol Metab,2001,86:3257-3265.
20 Park CW ,Kim JH ,Lee JH ,et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent. [J]. Diabetologia. 2000,43(12):1544-53.
1.叶山东、朱禧星主编。临床糖尿病学。第一版。合肥:安徽科学技术出版社。2005,11-141
2.Jeschke MG,Einspanier R,Klein D,et al.Insulin attenuates the systemic inflammatory response to thermal trauma[J].Mol Med,2002,8:443-450
3.李秀钧,邬元红.糖尿病是一种炎症性疾病.中华内分泌代谢杂志,2003,19(4):251-253
4 Brasier AR. The NF-kappaB regulatory network.Cardiovasc Toxicol. 2006, 6(2):111-3
5 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7
6 E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
7 Iwasaki Y, Kambayashi M, Asai M,et al.High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro. J Diabetes Complications. 2007,Jan-Feb;21(1):56-62.
8 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
9 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
10 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
11 Wang YY, Lin SY, Liu PH, et al.Association between hematological parameters and metabolic syndrome components in a Chinese population.J Diabetes Complications 2004 Nov-Dec;18(6):322-327.
12 Dandona P,Aljada A,Mohanty P,et al.Insulin inhibits intranunclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects:evidence for an anti-inflammatory effect[J] J Clin Endocrinol Metab,2001,86:3257-3265
13 A ljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF-Kb and MCP-1 expression in human aortic endothelial cells. [J]. Clin Endocrinol Metab,2001,86(1):450-453.
1 Chen F,Castranova V,Shi X.[J]. New insights into the role of nuclear factor-kappaB in cell growth regulation.Am J Pathol,2001,159(2) :387-97 .
2 De Martin R, Hoeth M , Hofer-Warbinek R, et al. The transcription factor NF-kappa B and the regulation of vascular cell function. [J]. Arterioscler Thromb Vasc Biol, 2000,20(11):E83-8.
3 Wu C, Ghosh S. Differential phosphorylation of the signal-responsive domain of I kappa B alpha and I kappa B beta by I kappa B kinases. [J]. J Biol Chem, 2003, 22;278(34):31980-7.
4 Tucker Collins,Myron I,Cybulsky. The NF- kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic .[J]. J Clin Invest ,2001 ,107(3) : 255-256.
5 Bierhaus A, Schiekofer S, Schwaninger M,et al. Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor- kappa B .[J]. Diabetes, 2001, 50(12): 2792-2808 .
6Ho E, Bray TM . NF-κB activation and diabetogenesis. [J]. Soc Exp Biol Med, 1999,222(3):205-13.
7 Nitenberg A. Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment .[J]. Presse Med, 2005 ,34(21):1654-61.
8 Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factorκappa B activation selectively regulates proinflammatory and prothrombotic responses in humanatherosclerosis [J]. Proc Natl Acad Sci U S A,2004,101(15) :5634-9.
9 Wilson SH, Caplice NM, Simari RD, et al. Activated nuclear factor- kappaB is present in the coronary vasculature in experimental hypercholesterolemia. [J]. Atherosclerosis, 2000, 148(1):23.
10 Lu C, He JC, Cai W ,et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. [J]. Proc Natl Acad Sci USA, 2004,101(32):11767-72.
11 Park CW ,Kim JH ,Lee JH ,et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent. [J]. Diabetologia. 2000,43(12):1544-53.
12 Usui H, Shikata K, Matsuda M ,et al. HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats [J]. Nephrol Dial Transplant. 2003 Feb;18(2):265-72 .
13 Viedt C, Dechend R, Fei J , et al. MCP-1 Induces Inflammatory Activation of Human Tubular Epithelial Cells: Involvement of the Transcription Factors, Nuclear Factor-{kappa}B and Activating Protein-1 [J]. Am Soc Nephrol 2002 Jun;13(6): 1534–1547.
14 Lee FT,Cao Z,Long DM,et al. Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. [J]. J Am Soc Nephrol, 2004,15(8):2139-51.
15E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
16 Lee S, Kim B, Sik Y, et al. High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells [J]. Kidney Int,2001,60:55-64.
17 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
18 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
19 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes,2006,55(3):760-7.
20 Silswal N, Singh AK, Aruna B,et al. Human resistin stimulates the. pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages. by NF-kappaB-dependent pathway. [J]. Biochem Biophys Res Commun, 2005, 334(4): 1092-101.
21 Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates lkappaB in mononuclear cells in obese subjects:evidence for an antiinflammatory effect? [J]. Clin Endocrinol Metab,2001,86:3257-3265.
22 Ha H, Yu M,,Choi Y , et al. Role of high glucose-induced nuclear factor-κB activation in monocyte chemoattractant protein-1 expression by mesangial cells. [J]. Am Soc Nephrol 2002 Apr;13(4):894-902.
23 Ruan H, Pownall HJ, Lodish HF. Troglitazone antagonizes tumor necrosis factor-alpha-induced. reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of. NF-kappaB. [J].J Biol Chem, 2003 ,278(30):28181-92.
24 Mohanty P, Aljada A, Ghanim H. Evidence for a potent anti-inflammatory effect of rosiglitazone. [J]. J Clin Endocrinol Metab,2004,89(6):2728-35.
25 Gruden G, Setti G, Hayward A ,et al. Mechanical stretch induces monocyte chemoattractant activity via an NF-kappaB-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells:inhibition by rosiglitazone. [J]. J Am Soc Nephrol, 2005,16(3):688-96.
26 A ljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF-Kb and MCP-1 expression in human aortic endothelial cells. [J]. Clin Endocrinol Metab,2001,86(1):450-453.
27 Cohen-Lahav M, Shany S, Tobvin D, et al. Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels. [J]. Nephrol Dial Transplant, 2006,21(4):889-97.
28 Kirin Yee, Michael Permezel, et al. Sulphasalazine And BAY 11-7082 Interfere With The NF-kappaB and IKK-βPathway To Regulate The Release Of Pro-Inflammatory Cytokines From Human Adipose Tissue And Skeletal Muscle, In Vitro. [J]. Endocrinology , 2004 ,146(3):1491–7.
29 Wu L, Noyan Ashraf MH, Facci M ,et al. Dietary phase 2 enzyme inducer and its cardiovascular protective effect in stroke prone SHR. [J]. Proc Natl Acad Sci U S A,2004, 101(18):7094-9.
2 Nitenberg A. Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment .[J]. Presse Med, 2005 ,34(21):1654-61.
3 Ho E, Bray TM . NF-κB activation and diabetogenesis. [J]. Soc Exp Biol Med, 1999,222(3):205-13.
4 De Martin R, Hoeth M , Hofer-Warbinek R, et al. The transcription factor NF-kappa B and the regulation of vascular cell function. [J]. Arterioscler Thromb Vasc Biol, 2000,20(11):E83-8.
5 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.
6 Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factorκappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis [J]. Proc Natl Acad Sci U S A,2004,101(15) :5634-9.
7 Wilson SH, Caplice NM, Simari RD, et al. Activated nuclear factor- kappaB is present in the coronary vasculature in experimental hypercholesterolemia. [J]. Atherosclerosis, 2000, 148(1):23.
8 Brasier AR. The NF-kappaB regulatory network.Cardiovasc Toxicol. 2006, 6(2):111-3
9 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
10 E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
11 Lee S, Kim B, Sik Y, et al. High glucose induces MCP-1 expression partly viatyrosine kinase-AP-1 pathway in peritoneal mesothelial cells [J]. Kidney Int,2001,60:55-64.
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 Lu C, He JC, Cai W ,et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. [J]. Proc Natl Acad Sci USA, 2004,101(32):11767-72.
14 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.
15 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
16 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
17 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
18 Silswal N, Singh AK, Aruna B,et al. Human resistin stimulates the. pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages. by NF-kappaB-dependent pathway. [J]. Biochem Biophys Res Commun, 2005, 334(4): 1092-101.
19 Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates lkappaB in mononuclear cells in obese subjects:evidence for an antiinflammatory effect? [J]. Clin Endocrinol Metab,2001,86:3257-3265.
20 Park CW ,Kim JH ,Lee JH ,et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent. [J]. Diabetologia. 2000,43(12):1544-53.
1.叶山东、朱禧星主编。临床糖尿病学。第一版。合肥:安徽科学技术出版社。2005,11-141
2.Jeschke MG,Einspanier R,Klein D,et al.Insulin attenuates the systemic inflammatory response to thermal trauma[J].Mol Med,2002,8:443-450
3.李秀钧,邬元红.糖尿病是一种炎症性疾病.中华内分泌代谢杂志,2003,19(4):251-253
4 Brasier AR. The NF-kappaB regulatory network.Cardiovasc Toxicol. 2006, 6(2):111-3
5 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7
6 E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
7 Iwasaki Y, Kambayashi M, Asai M,et al.High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro. J Diabetes Complications. 2007,Jan-Feb;21(1):56-62.
8 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
9 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
10 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes, 2006,55(3):760-7.
11 Wang YY, Lin SY, Liu PH, et al.Association between hematological parameters and metabolic syndrome components in a Chinese population.J Diabetes Complications 2004 Nov-Dec;18(6):322-327.
12 Dandona P,Aljada A,Mohanty P,et al.Insulin inhibits intranunclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects:evidence for an anti-inflammatory effect[J] J Clin Endocrinol Metab,2001,86:3257-3265
13 A ljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF-Kb and MCP-1 expression in human aortic endothelial cells. [J]. Clin Endocrinol Metab,2001,86(1):450-453.
1 Chen F,Castranova V,Shi X.[J]. New insights into the role of nuclear factor-kappaB in cell growth regulation.Am J Pathol,2001,159(2) :387-97 .
2 De Martin R, Hoeth M , Hofer-Warbinek R, et al. The transcription factor NF-kappa B and the regulation of vascular cell function. [J]. Arterioscler Thromb Vasc Biol, 2000,20(11):E83-8.
3 Wu C, Ghosh S. Differential phosphorylation of the signal-responsive domain of I kappa B alpha and I kappa B beta by I kappa B kinases. [J]. J Biol Chem, 2003, 22;278(34):31980-7.
4 Tucker Collins,Myron I,Cybulsky. The NF- kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic .[J]. J Clin Invest ,2001 ,107(3) : 255-256.
5 Bierhaus A, Schiekofer S, Schwaninger M,et al. Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor- kappa B .[J]. Diabetes, 2001, 50(12): 2792-2808 .
6Ho E, Bray TM . NF-κB activation and diabetogenesis. [J]. Soc Exp Biol Med, 1999,222(3):205-13.
7 Nitenberg A. Endothelial dysfunction in patients with diabetes: identification, pathogenesis and treatment .[J]. Presse Med, 2005 ,34(21):1654-61.
8 Monaco C, Andreakos E, Kiriakidis S, et al. Canonical pathway of nuclear factorκappa B activation selectively regulates proinflammatory and prothrombotic responses in humanatherosclerosis [J]. Proc Natl Acad Sci U S A,2004,101(15) :5634-9.
9 Wilson SH, Caplice NM, Simari RD, et al. Activated nuclear factor- kappaB is present in the coronary vasculature in experimental hypercholesterolemia. [J]. Atherosclerosis, 2000, 148(1):23.
10 Lu C, He JC, Cai W ,et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. [J]. Proc Natl Acad Sci USA, 2004,101(32):11767-72.
11 Park CW ,Kim JH ,Lee JH ,et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-kappa B-dependent. [J]. Diabetologia. 2000,43(12):1544-53.
12 Usui H, Shikata K, Matsuda M ,et al. HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats [J]. Nephrol Dial Transplant. 2003 Feb;18(2):265-72 .
13 Viedt C, Dechend R, Fei J , et al. MCP-1 Induces Inflammatory Activation of Human Tubular Epithelial Cells: Involvement of the Transcription Factors, Nuclear Factor-{kappa}B and Activating Protein-1 [J]. Am Soc Nephrol 2002 Jun;13(6): 1534–1547.
14 Lee FT,Cao Z,Long DM,et al. Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. [J]. J Am Soc Nephrol, 2004,15(8):2139-51.
15E. ZEENDER, K. MAEDLER, D. BOSCO, et al. Pioglitazone and sodium salicylate protect human beta-cells against apoptosis and impaired function induced by glucose and interleukin-1beta. [J]. J Clin Endocrinol Metab ,2004,89(10):5059-66.
16 Lee S, Kim B, Sik Y, et al. High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in peritoneal mesothelial cells [J]. Kidney Int,2001,60:55-64.
17 Chen F. Is NF-kappaB a culprit in type 2 diabetes? [J].Biochem Biophys Res Commun, 2005, 332(1):1-3.
18 Insheng Yuan, Konstantopoulos N , Jongsoon Lee, et al. Reversal of obesity and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ.[J].Science ,2001,293:1673-1677.
19 Sriwijitkamol A, Christ-Roberts C, Berria R ,et al. Reduced skeletal muscle inhibitor of KappaB beta content is. associated with insulin resistance in subjects with type 2 diabetes .[J]. Diabetes,2006,55(3):760-7.
20 Silswal N, Singh AK, Aruna B,et al. Human resistin stimulates the. pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages. by NF-kappaB-dependent pathway. [J]. Biochem Biophys Res Commun, 2005, 334(4): 1092-101.
21 Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates lkappaB in mononuclear cells in obese subjects:evidence for an antiinflammatory effect? [J]. Clin Endocrinol Metab,2001,86:3257-3265.
22 Ha H, Yu M,,Choi Y , et al. Role of high glucose-induced nuclear factor-κB activation in monocyte chemoattractant protein-1 expression by mesangial cells. [J]. Am Soc Nephrol 2002 Apr;13(4):894-902.
23 Ruan H, Pownall HJ, Lodish HF. Troglitazone antagonizes tumor necrosis factor-alpha-induced. reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of. NF-kappaB. [J].J Biol Chem, 2003 ,278(30):28181-92.
24 Mohanty P, Aljada A, Ghanim H. Evidence for a potent anti-inflammatory effect of rosiglitazone. [J]. J Clin Endocrinol Metab,2004,89(6):2728-35.
25 Gruden G, Setti G, Hayward A ,et al. Mechanical stretch induces monocyte chemoattractant activity via an NF-kappaB-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells:inhibition by rosiglitazone. [J]. J Am Soc Nephrol, 2005,16(3):688-96.
26 A ljada A, Saadch R, Ghaninm H, et al. Insulin inhibits NF-Kb and MCP-1 expression in human aortic endothelial cells. [J]. Clin Endocrinol Metab,2001,86(1):450-453.
27 Cohen-Lahav M, Shany S, Tobvin D, et al. Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels. [J]. Nephrol Dial Transplant, 2006,21(4):889-97.
28 Kirin Yee, Michael Permezel, et al. Sulphasalazine And BAY 11-7082 Interfere With The NF-kappaB and IKK-βPathway To Regulate The Release Of Pro-Inflammatory Cytokines From Human Adipose Tissue And Skeletal Muscle, In Vitro. [J]. Endocrinology , 2004 ,146(3):1491–7.
29 Wu L, Noyan Ashraf MH, Facci M ,et al. Dietary phase 2 enzyme inducer and its cardiovascular protective effect in stroke prone SHR. [J]. Proc Natl Acad Sci U S A,2004, 101(18):7094-9.