白细胞介素-2改善糖尿病大鼠血管内皮依赖性舒张功能

TREATMENT WITH INTERLEUKIN-2 AMELIORATES ENDOTHELIUM-DEPENDENT VASORELAXATION OF AORTA IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

目的研究白细胞介素-2(interleukin-2,IL-2)对链脲佐菌素诱导的早期I型糖尿病大鼠离体胸主动脉内皮依赖性舒张功能的影响及其可能机制。方法雄性SD大鼠(200-250g),随机分成正常对照组,IL-2对照组,糖尿病模型组,低剂量IL-2(5×103U·kg-1.d-1sc)处理组,高剂量IL-2(5×104U·kg-1.d-1sc)处理组。各组大鼠饲养5周后,取胸主动脉离体灌流并通过PowerLab生物信号采集系统记录张力变化,检测其对乙酰胆碱(ACh)诱导的内皮依赖性舒张反应,及对硝普钠(SNP)诱导的非内皮依赖性舒张反应。并测定血清一氧化氮(NO)含量、总超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)活性。结果IL-2处理后对糖尿病大鼠血糖无明显影响,但能减少糖尿病引起的体重下降。糖尿病模型组胸主动脉对ACh诱导的舒张反应明显减弱,IL-2能明显改善糖尿病胸主动脉的这一内皮依赖性舒张反应;各组对SNP诱导的非内皮依赖性舒张反应无显著差异。糖尿病大鼠血清NO水平显著降低,IL-2处理后能明显提高血清NO水平。但是IL-2处理并不能有效抑制糖尿病大鼠血清SOD及GSH-PX活性的下降。结论IL-2处理糖尿病大鼠5周后,能显著改善糖尿病大鼠主动脉对ACh诱导的内皮依赖性舒张反应,这可能与其改善内皮功能有关,但与改变抗氧化能力无关。

To investigate the changes in aortic functions in streptozotocin（STZ）-induced diabetic rats and the effect of interleukin-2 （IL-2） on them, we observed the vasorelaxation of aorta to acetylcholine（ACh） and sodium nitroprusside（SNP）. Methods： Male Sprague-Dawley rats were randomly divided into a normal control group, an IL-2 control group, a diabetic group, and diabetic groups administered with a low dose（5×10^3U·kg^-1·d^-1Sc） or a high dose of IL-2（5×10^4U·kg^-1·d^-1Sc） for five weeks. Aortic rings were isolated for use in vitro isometric force recording studies, and endothelium-dependent relaxation induced by ACh and endothelium-independent relaxation induced by SNP were measured. The serum nitric oxide（NO） levels and the activities of serum superoxide dismutase（SOD） and glutathione peroxidase（GSH-PX）were measured. Results： ACh caused a dose-dependent relaxation that was weakened in the diabetic group. The IL-2 treated groups were less weakened. However, the endothelium-independent relaxation induced by SNP was not significantly different in aortae of all groups. The serum NO levels were significantly increased in diabetic rats treated with IL-2 when compared with diabetic group, but the serum SOD and GSH-PX activities were not improved in diabetic group with IL-2. Conclusion： IL-2 can improve the aortic endothelium-dependent relaxation in diabetic rats, which involved the improvement of endothelial function in aorta, other than the alteration of anti-oxidative capacity.