Quan Shou, Kaminski Pawel M, Yang Liming, Morita Toshisuke, Inaba Muneo, Ikehara Susumu, Goodman Alvin I, Wolin Michael S, Abraham Nader G
Department of Pharmacology, New York Medical College, Valhalla, NY, USA.
Biochem Biophys Res Commun. 2004 Mar 5;315(2):509-16. doi: 10.1016/j.bbrc.2004.01.086.
Heme oxygenase-1 (HO-1) represents a key defense mechanism against oxidative injury. Hyperglycemia has been linked to increased oxidative stress, leading to endothelial dysfunction, delayed cell replication, and enhanced apoptosis. The effect of streptozotocin (STZ)-induced diabetes on HO activity, HO-1 promoter activity, superoxide anion (O*-2, and the number of circulating endothelial cells was measured. The expression of HO-1/HO-2 protein was unchanged, but HO activity was decreased in aortas of diabetic rats compared with control (p < 0.05). High glucose decreased HO-1 promoter activity (p < 0.05). Hyperglycemia increased O*-2 and this increase was augmented with HO-1 inhibition and diminished with HO-1 upregulation (p < 0.05). Circulating endothelial cells were significantly higher in diabetic rats and were decreased or increased with administration of the HO-1 inducer (CoPP) or inhibitor (SnMP), respectively (p<0.05). In conclusion, HO-1 upregulation in diabetic rats brings about an increase in serum bilirubin, a reduction in O*-2 production, and a decrease in endothelial cell sloughing.
血红素加氧酶-1（HO-1）是抵御氧化损伤的关键防御机制。高血糖与氧化应激增加有关，可导致内皮功能障碍、细胞复制延迟及细胞凋亡增加。本研究检测了链脲佐菌素（STZ）诱导的糖尿病对HO活性、HO-1启动子活性、超氧阴离子（O₂⁻）及循环内皮细胞数量的影响。糖尿病大鼠主动脉中HO-1/HO-2蛋白表达未发生改变，但与对照组相比，HO活性降低（p<0.05）。高糖降低了HO-1启动子活性（p<0.05）。高血糖使O₂⁻增加，HO-1抑制时这种增加更为明显，HO-1上调时则减少（p<0.05）。糖尿病大鼠循环内皮细胞显著增多，给予HO-1诱导剂（CoPP）或抑制剂（SnMP）后分别减少或增加（p<0.05）。总之，糖尿病大鼠HO-1上调可使血清胆红素增加、O₂⁻生成减少及内皮细胞脱落减少。
