糖尿病心肌病患者外周血单个核细胞E26转录因子1的表达及其意义

Expression of E26 transcription factor-1 in peripheral blood mononuclear cell of the patients with diabetic cardiomyopathy

目的探讨糖尿病心肌病（DCM）与外周血单个核细胞E26转录因子（Ets）1的表达相关性，初步探讨Ets．1在DCM发病机制中可能的作用，为临床诊治DCM提供新的思路。方法选择2010年l一12月广东医学院附属医院DCM患者28例（DCM组）、单纯2型糖尿病患者30例（2型糖尿病组）和同期体检健康者30例（对照组）。采用SYBRGreenI实时荧光定量逆转录聚合酶链反应检测外周血单个核细胞Ets．1mRNA表达，记录其他临床及实验室生化指标。结果①DCM组LDL—C、TG高于对照组，二尖瓣舒张早期血流速度峰值／舒张晚期血流速度峰值（E／A）比值低于对照组，组间差异均有统计学意义[LDL—C：（3．3±1．2）mmol／L比（2．5±0．8）mmol／L，TG：（3．5±1．8）mmol／L比（1．8±0．6）mmol／L，E／A：（0．45±0．14）比（1．24±0．16），均P〈0．05]；DCM组和2型糖尿病组空腹血糖（FBG）、糖化血红蛋白（HbAlc）均高于对照组，组间差异均有统计学意义[DCM组分别为（8．7±3．6）mmol／L和（8．5±2．6）％，2型糖尿病组分别为（9．0±2．5）mmol／L和（9．0±1．6）％，对照组分别为（5．4±1．2）mmol／L和（5．3±1．2）％，均P〈0．05]。DCM组E／A低于2型糖尿病组（0．93±0．34），组间差异有统计学意义（P〈0．05）。②DCM组单个核细胞Ets．1mRNA表达明显高于对照组，组间差异有统计学意义（0．58±0．17比0．42±0．15，P〈0．05）；DCM组和2型糖尿病组基质金属蛋白酶（MMP）9表达[（3．7±0．8）、（2．1±0．6）斗∥L]均明显高于对照组[（1．5±0．5）峙／L]，差异均有统计学意义（均P〈0．05），DCM组与2型糖尿病组间差异无统计学意义（P〉0．05）。~DCM患者Ets．1mRNA表达与MMP-9呈正相关（r=0．81，P=0．03），与E／A比值、FBG、HbAlc、LDL-C、TG无相关性（r值分别为旬．52、0．73、0．26、0．06、0．72，均P〉0．05）。~DCM危险因素分析结果显示Ets-1mRNA高表达为危险因素[比值比=3．12，95％置信区间：2．14—4．48，P〈0．05]。结论Ets一1可上调MMP-9表达，参与2型糖尿病的发生发展，Ets．1可作为DCM的早期预测因子。

Objective To primarily discuss the role of E26 transcription factor （Ets） 1 in peripheral blood mononuclear cell of the patients with diabetic cardiomyopathy（DCM） and to provide the new measure to cure DCM. Methods DCM group （ n = 28） and type 2 diabetic mellitus （T2DM） group （ n = 30）, control group （ n = 30）. The expression of Ets-1 mRNA on peripheral-blood mononuclear cells was examined by SYBR Green I real-time quantitative reverse transcription ploymerse chain reaction. Results The levels of low density lipoprotein cholesterol （LDL-C） and triglyceride（TG） in DCM group were significantly higher than those in control group, the E/A in DCM group was significantly lower than that in control group[ LDL-C： （3.3 ＋ 1.2）mmol/L vs （2.5 ＋ 0.8 ）mmol/L, TG： （3.5 ＋ 1.8） mmol/L vs （1.8 ~0.6） retool/L, E/A： （0.45 ＋0.14）vs（ 1.24 ~0.16）, P 〈0.05 ]. The levels of fasting blood glucose（FBG） and glycosylated hemoglobin（Hb） Alc in DCM and T2DM groups were significantly higher than those in control group [ DCM group （ 8.7 ＋ 3.6 ） mmol/L and （ 8.5 ＋ 2.6） %, T2DM （ 9.0 ＋ 2.5 ） mmol/L and （9.0 ＋ 1.6） %, control group （5.4 ~ 1.2 ） mmol/L and （ 5.3 ~ 1.2） %, P 〈 0.05 ]. The E/A in DCM group was significantly lower than that in T2DM group（0.93 -sO. 34） （P 〈0.05 ）. The expression of Ets-1 mRNA on pe- ripheral-blood mononuclear cells in DCM group were significantly higher than that in control group （0.58 ~ 0.17 vs 0.42 ~0.15, P 〈0.05）. The expression of matrix metalloproteinase（ MMP）9 in DCM group and T2DM group were significantly higher than those in control group [ （ 3.7 ~ 0.8 ） txg/L and （ 2. 1 ~ 0. 6 ） Ixg/L vs （ 1.5 ＋ 0.5 ） txg/L, P 〈 0.05 ], there were not statistically significant between DCM group and T2DM group （ P 〈 0.05 ）. The expres- sion of Ets-1 were correlated positively with MMP-9 in DCM （r = 0.81, P = 0.03 ）, and there were not correlated positively with E/A, FBG, HbAlc, LDL-C and TG （r = -0.52, 0.73, 0.26, 0.06, 0.72, all P 〉0.05）. Logistic regression analysis showed that Ets-1 was high risk factors of DCM [ odd ratio （OR） = 1.31, 95% confi-donce interval （CI） ：2.14-d. 48, P 〈 0.05 ]. Conclusion Ets-1 can up-regulate the expression of MMP-9 in the progress of DM, but only Ets-1 can be a predictor of DCM.