【作者】 林杨；

【导师】 叶山东；

【作者基本信息】 安徽医科大学 ， 内科学， 2008， 硕士

【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。更多还原

【Abstract】 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.更多还原