强化胰岛素治疗对脓毒症患者血管内皮细胞功能的影响

Effects of intensive insulin therapy on the functions of vascular endothelial cells in septic patients.

目的研究强化胰岛素治疗（IIT）对脓毒症患者血管内皮细胞（VEC）功能的影响。方法将120例脓毒症患者随机分为强化胰岛素治疗1组（IIT1组）、强化胰岛素治疗2组（IIT2组）及常规胰岛素治疗组（CIT组），在治疗前及治疗后3、7d用酶联免疫吸附双抗体夹心法（ELISA）检测3组患者各时相点血清血管性假血友病因子（vWF）、血栓调节蛋白（TM）、内皮素-1（ET-1）和一氧化氮（NO）的含量。同时观察3组患者28d病死率、ICU住院时间、机械通气时间、△APACHEII评分和／kMODS评分。结果相对于CIT组患者，IIT1与IIT2组患者血清的vWF、TM和ET-1明显降低[CIT、IIT1与IIT2组vWF分别为：治疗后3d（142．57±10．07）％、（137．32±9．66）％、（138．32±8．80）％，治疗后7d（126．27±10．49）％、（116．55±9．36）％、（120．72±9．53）％；TM：治疗后3d（6．87±1．62）、（5．95±1．60）、（6．17±1．33）μg／L，治疗后7d（4．55±1．48）、（3．35±0．94）、（3．87±1．20）μg／L；ET-1：治疗后3d（61．27±9．20）、（55．97±9．03）、（57．37±7．70）ng／L，治疗后7d（43．12±6．17）、（33．77±6．20）、（35．95±5．73）ng／L；P均〈0．05]、NO明显升高[治疗后3d（37．77±8．17）、（42．75±9．92）、（41．80±8．66）μmol／L，治疗后7d（54．42±8．46）、（64．90±9．63）、（61．20±8．84）μmol／L；P均〈0．05]，但两个亚组之间无明显差异（P〉0．05）；同时，CIT、IIT1与IIT23组患者28d病死率（分别为20．O％、12．5％、45．O％，0=8．82）、ICU住院时间[分别为（9．50±3．70）、（7．72±3．29）、（8．02±2．90）d，F值为3．28]、机械通气时间[分别为（8．92±3．79）、（7．23±3．32）、（7．37±2，99）d，F值为3．09]、△APACHE1I评分[分别为8．87±3．46、7．20±2．81、7．42±3．18，F值为3．30]和／XMODS评分[分别为4．15±2．15、3．20±1．48、3．32±1．74，F值为3．23]差异具有统计学意义（P均〈0．05），且IIT1、IIT2组与CIT组比较，差异均有统计学意义（P均〈0．05），但两个亚组之间差异无统计学意义（P〉0．05）。结论IIT对脓毒症患者VEC具有保护作用，且将血糖控制在6．6～8．3mmol／L可以明显降低低血糖的发生率，同时IIT可以明显改善脓毒症患者的价值。

Objective To investigate the effects of intensive insulin therapy on the functions of vascular endothelial cells in septic patients. Methods One hundred and twenty septic patients were randomly assigned to intensive insulin therapy 1, intensive insulin therapy 2 and conventional insulin therapy, serum yon Willebrand factor （vWF） ,thrombomodulin protein（TM） , endothelin-1 （ ET-1 ） and nitric oxide （ NO ） of the three groups of patients were determined by enzyme-linked immunoadsorbent assay double antibody sandwich principle （ELISA） before treatment and the next 3 d,7 d after treatment. At the same time we observed the three groups of patients with 28-d mortality,the days of hospitalized in ICU,number of days for using mechanical ventilation, AAPACHE II score and AMODSscore. Results After treatment of 3 days, vWF was （142.57 ± 10.07）%,（137.32 ±9.66）% and （138.32 ±8. 80）% in the CIT,IIT1 and IIT2 group,respectively. After treatment of 7 days,vWF was （ 126. 27 ± 10.49）% ,（116.55± 9.36）% and （ 120.72 ±9.53）% in the CIT, IIT1 and lIT2 group, respectively. After treatment of 3 days,TM was（6. 87 ±1.62） tzg/L, （5.95 ± 1.60）μg/L and （6. 17 ±1.33）μg/L in the CIT, IIT1 and IIT2 group, respectively. After treatment of 7 days, TM was （ 4.55 -±1.48 ）μg/L, （ 3.35± 0. 94 ） μg/L and （3.87± 1.20） μg/L in the CIT, IITI and IIT2 group, respectively. After treatment of 3 days, ET-1 was （ 61.27 ±9. 20） rig/L, （55.97 ±9. 03 ） ng/L and （ 57. 37 ±7.70 ） ng/L in the CIT, IIT1 and III2 group, respectively. After treatment of 7 days,TM was（43.12±6. 17）ng/L, （33.77 ±6. 20） ng/L and （35.95±5.73） ng/L in the CIT,IIT1 and IIT2 group, respectively. Compared with conventional insulin therapy, vWF, TM and ET-1 were significantly decreased （P 〈0. 05）,NO were significantly higher （P 〈 0. 05 ）in IIT1 and IIT2,but the two sub-groups had no significant difference （P 〉 0. 05）. In the CIT, IIT1 and IIT2 groups respectively, the mortality at 28 days were 20. 0% , 12. 5% and 45.0%, the days of hospitalized in ICU were （9. 50± 3.70） d, （ 7.72 ± 3.29 ） d and （ 8.02 ± 2. 90）d,number of day for using mechanicai ventilation were （8.92 ±3.79） d, （7.23± 3.32） d and （7.37± 3.29） d, AAPACHE II score were 8.87 ± 3.46,7.20± 2.81 and 7.42 ± 3.18, A MODS score were 4. 15 ± 2. 15, 3.20±1.48 and 3.32 ± 1.74, with significant differences （P 〈 0. 05 ）. These indices were significantly decreased （ P 〈 0. 05 ） in IIT1 and IIT2, but the two sub-groups also had no significant differences （ P 〉 0. 05 ）. Conclusions Intensive insulin therapy on patients with sepsis has a protective effect of vascular endothelial cells, and the blood glucose controlled in the 6. 6 -8.3 mmol/L can significantly decrease the incidence of hypoglycemia, and intensive insulin therapy can also significantly improve the prognosis of patients with sepsis.