【摘要】 目的 探讨应用抗氧化剂N-乙酰半胱氨酸（N-acetylcysteine,NAC）之后对血糖波动导致的血管内皮变化的影响。方法 于2008年1月—2009年12月选取雄性Wistar大鼠24只，按照每组6只随机分为4组，A组（对照组）输注生理盐水；B组（急性血糖波动组）需要间断输注葡萄糖；C组（NAC干预组1）需要持续输注NAC(0.35 mg/kg·min)及间断葡萄糖输注；D组（NAC干预组2）需要持续输注NAC(0.7 mg/kg·min)及间断葡萄糖输注。维持对照组的血糖在5.5 mmol/L左右，调节另外3组的血糖波动在5.5～20.0 mmol/L。在大鼠清醒状态下输液总共48 h，留取主动脉作为标本。应用比色法检测NO和GSH-PX,Elisa法检测TNF-α和IL-6，免疫组化方法检测，iNOS,TUNEL法检测主动脉内皮细胞的凋亡情况。结果 急性血糖波动组的NO(2.83±0.48)μmol/L、TNF-α(35.13±2.16)pg/mL、IL-6(20.56±3.78)pg/mL水平较对照组的NO(1.11±0.14)μmol/L、TNF-α(17.66±1.09)pg/mL、IL-6(9.82±0.61)pg/mL显著升高，iNOS表达也显著升高，差异有统计学意义（P<0.05）；急性血糖波动组的GSH-PX(6.26±0.38) nmol/mgprot水平较对照组(10.02±1.10)nmol/mgprot显著降低，差异有统计学意义（P<0.05）；在急性血糖波动组的主动脉内皮中检测到凋亡细胞。应用NAC后以上情况可改善，大小剂量NAC比较差异无统计学意义（P>0.05）。结论 血糖波动可增强主动脉内皮细胞中的炎症和氧化应激反应，从而导致凋亡，应用抗氧化剂NAC后可改善。更多还原

【Abstract】 Objective To explore the effects of application of antioxidant N-acetylcysteine(NAC) on vascular endothelial changes induced by blood glucose fluctuations. Methods From January 2008 to December 2009, twenty-four male Wistar rats were selected and randomly divided into four groups according to 6 in each group.Group A(control group)was injected with normal saline. Group B(acute glucose fluctuation group) needed intermittent glucose infusion.Group C(NAC intervention group 1) required continuous NAC infusion(0.35 mg/kg·min) and intermittent glucose infusion. Group D(NAC intervention group 2) required continuous NAC(0.7 mg/kg·min) infusion and intermittent glucose infusion. The control group maintained blood glucose at around 5.5 mmol/L and the other three groups adjusted blood glucose fluctuations between 5.5-20.0mmol/L. The rats were given fluids for a total of 48 hours while awake,and the aorta was retained as a specimen. NO and GSH-PX were detected by colorimetry, TNF-αand IL-6 were detected by Elisa, iNOS was detected by immunohistochemistry, and the apoptosis of aortic endothelial cells was detected by TUNEL. Results The level of NO(2.83±0.48) μmol/L, TNF-α(35.13±2.16) pg/mL,I L-6(20.56±3.78) pg/mL in the acute glucose fluctuation group were significantly increased than the control group NO(1.11±0.14) μmol/L TNF-α(17.66±1.09) pg/mL, IL-6(9.82±0.61) pg/mL. The expression of iNOS was also significantly increased, and the difference was statistically significant(P<0.05); and the GSH-PX(6.26±0.38) nmol/mgprot level in the acute glucose fluctuation group was significantly lower than that in the control group(10.02±1.10) nmol/mgprot, and the difference was statistically significant(P<0.05). Apoptotic cells were detected in the aortic endothelium of the acute blood glucose fluctuation group. The above conditions could be improved after the application of NAC, and there was no significant difference between the large and small doses of NAC(P>0.05). Conclusion Blood glucose fluctuations enhance inflammatory and oxidative stress responses in aortic endothelial cells leading to apoptosis,which is improved by the application of the antioxidant NAC.更多还原