血红素加氧酶1在高糖和糖基化终产物致人单核细胞氧化应激中的作用

目的探讨血红素加氧酶1（HO-1）高表达在对抗高糖和糖基化终产物（AGEs）诱导的人单核细胞（THP-1）氧化应激中的作用。方法THP-1细胞分为对照（NC）组、GLU＋AGEs组、钴原卟啉（CoPP）＋GLU4-AGEs组和CoPP组4组，孵育24h后收集细胞及培养液上清，检测各组细胞的活性氧（ROS）产量、培养液上清丙二醛（MDA）和肿瘤坏死因子α（TNF-α）水平及HO-1表达。结果GLU4-AGEs组的ROS产量、MDA和TNF-α水平均显著高于NC组（P〈0．05）；CoPP4-GLU4-AGEs组的ROS产量和MDA水平均显著低于GLU4-AGEs组（P〈0．05）。GLU4-AGES组的HO-1基因和蛋白表达均显著高于NC组（P％0．01），CoPP4-GLU＋AGEs组的HO-1蛋白表达显著高于GLU4-AGEs组（P〈0．01）。结论CoPP通过诱导HO-1蛋白高表达拮抗高糖和AGEs导致的THP-1细胞氧化应激，通过诱导HO-1高表达可能拮抗糖尿病所致单核细胞氧化应激。

Effects of CoPP on oxidative injury induced by high glucose and AGEs in human monocyte THP-1 cells

Objective To investigate the effects of CoPP（cobalt protoporphyrin, being an inducer of heme oxygenase-1, HO-1 as an antioxygen agent） on oxidative injury in human monocyte THP-1 cells incubated with high glucose and advanced glycation end products （AGEs）. Methods There Were four groups ; control group, GLUt AGEs group （ 15 mmol/L glucose1 100μg/mL AGEs）, CoPP group （5.5 mmol/L glucose1 10 μmol/LCoPP） , CoPP＋ GLU＋ AGEs group （ 10 μmol/L CoPP＋ 15 mmol/L glucose ＋100 μg/mL AGEs）. Reactive oxygen species （ROS）, malondialdehyde （MDA） and tumor necrosis factor α （TNF-α） were determined and the expressions of HO-1 mRNA and protein were detected by RT- PCR and Western blotting, respectively. Results ROS output and MDA were significantly lower in CoPPIGLU1 AGEs gorup （95.42 ± 2. 36, 1.28 ± 0. 61 respectively） than in GLU＋ AGEs group （107.21±8. 9, 3.26 ± 0. 32） （all P〈0. 05）. CoPP＋ GLU1 AGEs group had significantly higher expressions of HO-1 protein than did GLUIAGEs group （P〈0.05）. Conclusions The oxidative injury and inflammation in human monocytoid THP-1 cells induced by high glucose and AGEs are suppressed by HO-1 inducer. The agents inducing high expression of HO-1 may antagonize the diabetes-induced oxidative injury.