Marmara University School of Pharmacy, Department of Pharmacology, Tıbbiye St. 49 Haydarpaşa, Istanbul 34688, Turkey.
Eur J Pharmacol. 2011 Jun 25;660(2-3):476-84. doi: 10.1016/j.ejphar.2011.03.030. Epub 2011 Apr 2.
Our aim was to investigate the role of oxidative stress and inflammation on the functional and biochemical changes caused by hyperglycemia in the aorta and corpus cavernosum tissues of streptozotozin diabetic rats and to determine if rosiglitazone and/or insulin treatment has any preventive effect on organ dysfunction. Wistar Albino rats were divided into 2 groups. I) Control group: a) Vehicle, 0.1 M citrate buffer, the solvent of streptozotocin injected intraperitoneally (i.p) and b) Rosiglitazone group: (4 mg/kg/day, i.p.) for 8 weeks. II) Diabetic group: streptozotocin (60 mg/kg) was administered i.p. to induce diabetes. 48 h after streptozotocin injection, animals were divided into 4 subgroups (n=6 for each group); a) no treatment group (D), b) treated with rosiglitazone (4 mg/kg/day) (DR), c) treated with insulin (6 U/kg/day) (DI) and d) treated with insulin and rosiglitazone (DRI) for 8 weeks. At the end of the experimental period, animals were decapitated and tissue samples were collected for in vitro experiments and biochemical studies. Endothelium dependent relaxation induced by acetylcholine in the aorta and corpus cavernosum tissues were attenuated in the diabetic group, whereas phenylephrine induced contractile responses were reduced. These responses were restored after rosiglitazone and/or insulin treatment, the combination being the most efficient treatment. Malondialdehyde and TNF-α levels were increased in diabetic rats while glutathione levels were decreased. All treatments prevented these changes in biochemical parameters, rosiglitazone and insulin combination again being the most efficient treatment. Our results suggested that supplementing diabetic patients receiving insulin treatment with adjunct therapy of rosiglitazone may have some benefit for controlling diabetic complications.
我们的目的是研究氧化应激和炎症在链脲佐菌素糖尿病大鼠主动脉和海绵体组织中高血糖引起的功能和生化变化中的作用,并确定罗格列酮和/或胰岛素治疗是否对器官功能障碍有预防作用。Wistar 白化大鼠分为 2 组。I)对照组:a)载体,0.1M 柠檬酸盐缓冲液,链脲佐菌素的溶剂(腹膜内注射,i.p)和 b)罗格列酮组:(4mg/kg/天,i.p)8 周。II)糖尿病组:链脲佐菌素(60mg/kg)腹膜内注射诱导糖尿病。链脲佐菌素注射后 48 小时,动物分为 4 个亚组(每组 6 只);a)无治疗组(D)、b)罗格列酮治疗组(4mg/kg/天)(DR)、c)胰岛素治疗组(6U/kg/天)(DI)和 d)胰岛素和罗格列酮治疗组(DRI)8 周。实验期末,断头处死动物,采集组织样本进行体外实验和生化研究。糖尿病组主动脉和海绵体组织中乙酰胆碱诱导的内皮依赖性舒张减弱,而苯肾上腺素诱导的收缩反应减弱。罗格列酮和/或胰岛素治疗后,这些反应得到恢复,联合治疗效果最佳。糖尿病大鼠丙二醛和 TNF-α水平升高,谷胱甘肽水平降低。所有治疗均预防了这些生化参数的变化,罗格列酮和胰岛素联合治疗效果最佳。我们的结果表明,在接受胰岛素治疗的糖尿病患者中补充罗格列酮辅助治疗可能对控制糖尿病并发症有益。