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2型糖尿病患者血糖波动与血管内皮损伤/血小板活化/PKCβ1表达的相关性研究

[Correlation Research on Blood Glucose Fluctuation in Type 2 Diabetes Mellitus Patients and Vas- cular Endothelial Injury/Platelet Activation/PKCβ1 Expression].

作者信息

Wang Jing-Shang, Huang Ye, Chen Ke-Ji, Sun Ming-Yue, Chen Shui-Ling, Yin Hui-Jun

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 Oct;36(10):1184-1190.

PMID:30641004
Abstract

Objective To observe the correlation between blood glucose fluctuation in type 2 dia- betes mellitus ( T2DM) patients and vascular endothelial injury/platelet activation/protein kinase Cβ1 (PKCpβ1). Methods Capillary blood was collected from finger tips of 38 T2DM patients at 7 time points, i.e., before 3 meals, 2 h after 3 meals, 21:00 pm before sleep. The mean amplitude of plasma glucose excursions (MAGE) was calculated. The peripheral blood platelet aggregation rate (PAG) induced by a- denosine diphosphate (ADP) and platelet membrane protein level of CD62p were determined by platelet fluorescent aggregometer and flow cytometry respectively. HbAlc was measured by ion-exchange high- performance liquid chromatography. Serum levels of E-selectin, von Willebrand factor ( vWF), and PKCβ1 were detected by ELISA. Meanwhile, liver and renal functions, blood lipids were also measured. Their blood pressure was measured and body mass index (BMI) calculated. By taking HbA1c as a moni- tored index for assessing long-term glucose control, MAGE as an indicator for assessing glucose fluctua- tion, the correlations between serum markers for vascular endothelial injury (levels of E-selectin and vWF)/platelet activation indices (PAG and CD62p expression) and PKCβ1 level/MAGE respectively were analyzed using Pearson correlation analysis and multivariant Logistic regression. The correlations be- tween PKCβ1 level and MAGE/HbA1 c were also analyzed. Results In simple correlation analysis, there were no significant correlations between age/BMI/course of disease/medical history/serum levels of E-se- lectin/vWF/PKCβ1/PAG/CD62p expression and MAGE (P >0. 05). There were significant correlations be- tween vascular endothelial injury markers ( E-selectin and vWF)/platelet activation indicators ( PAG, CD62p expression) and MAGE (r =0. 468, 0. 609, 0. 451 , 0. 674; P <0. 01). There were significant corre- lations between PKCβ1 and glucose assessment indicators (MAGE and HbA1c)/vascular endothelial inju- ry markers ( E-selectin and vWF) , platelet activation indicators ( PAG and CD62p expression) (r = 0. 643, 0. 705, 0. 394, 0. 665, 0. 441 , 0. 577; P <0. 01). Conclusion PKCβ1 , the key regulatory gene of coronary artery disease with blood stasis syndrome, was closely related with the degree of vascular en- dothelial injury and aggregation level of platelet activation in T2DM patients with blood glucose fluctuation.

摘要

目的 观察2型糖尿病(T2DM)患者血糖波动与血管内皮损伤/血小板活化/蛋白激酶Cβ1(PKCβ1)之间的相关性。方法 采集38例T2DM患者指尖毛细血管血,于三餐前、三餐后2小时、晚上21:00睡前共7个时间点采集。计算血糖波动幅度均值(MAGE)。分别采用血小板荧光聚集仪和流式细胞术检测二磷酸腺苷(ADP)诱导的外周血血小板聚集率(PAG)及血小板膜蛋白CD62p水平。采用离子交换高效液相色谱法测定糖化血红蛋白(HbAlc)。采用酶联免疫吸附测定法(ELISA)检测血清E-选择素、血管性血友病因子(vWF)及PKCβ1水平。同时检测肝肾功能、血脂。测量血压并计算体重指数(BMI)。以HbA1c作为评估长期血糖控制的监测指标,MAGE作为评估血糖波动的指标,采用Pearson相关分析和多变量Logistic回归分析血管内皮损伤血清标志物(E-选择素和vWF水平)/血小板活化指标(PAG和CD62p表达)与PKCβ1水平/MAGE之间的相关性。还分析了PKCβ1水平与MAGE/HbA1c之间的相关性。结果 简单相关分析显示,年龄/BMI/病程/病史/血清E-选择素/vWF/PKCβ1/PAG/CD62p表达水平与MAGE之间均无显著相关性(P>0.05)。血管内皮损伤标志物(E-选择素和vWF)/血小板活化指标(PAG、CD62p表达)与MAGE之间存在显著相关性(r=0.468、0.609、0.451、0.674;P<0.01)。PKCβ1与血糖评估指标(MAGE和HbA1c)/血管内皮损伤标志物(E-选择素和vWF)、血小板活化指标(PAG和CD62p表达)之间存在显著相关性(r=0.643、0.705、0.394、0.665、0.441、0.577;P<0.01)。结论 冠心病血瘀证关键调控基因PKCβ1与血糖波动的T2DM患者血管内皮损伤程度及血小板活化聚集水平密切相关。

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