可溶性鸟苷酸环化酶激活剂cinaciguat对糖尿病大鼠氧化应激的影响

Effect of soluble guanglate cyclase activator cinaciguat on oxidative stress of diabetic rats

目的分析可溶性鸟苷酸环化酶(soluble guanylate cyclase,s GC)激活剂cinaciguat对糖尿病大鼠氧化应激的影响。方法用高脂高糖饲料喂养及腹腔注射链脲佐菌素(streptozotocin,STZ)的方法建立2型糖尿病大鼠模型,随机分为模型组和cinaciguat低、中、高剂量[3.5、7、14μg/(kg·d)]组。各组大鼠饲养12周,cinaciguat干预14 d后,经下腔静脉采血,采用全自动生化分析仪检测大鼠血糖及血脂水平,比色法检测血清总氧化物歧化酶(superoxide dismu-tase,SOD)活性、丙二醛(malonaldehyde,MDA)含量,内皮素(endothelin-1,ET-1)ELISA试剂检测血浆ET-1含量。结果与模型组比较,cinaciguat各剂量组大鼠血糖值下降不明显(P均>0.05);甘油三酯(triglycerides,TG)和总胆固醇(cholesterol,TC)含量均明显降低(P均<0.05);cinaciguat各剂量组SOD活性明显升高,MDA及ET-1含量明显降低。结论 cinaciguat可能具有调节血脂,降低糖尿病大鼠氧化应激水平,改善血管内皮功能的作用。

Objective To analyze the effect of soluble guanglate cyclase on oxidative stress of diabetic rats. Methods Mouse model of type 2 diabetes mellitus was established by feeding with high lipid and high glucose diet and intraperitoneal injection with streptozotoein （STZ）. The model rats were randomly divided into as well as low [3.5 μg/（kg.d）], moderate [7 μg/（kg.d）] and high （14 μg/（kg.d）] dose cinaeiguat groups. The rats in various groups were raised for 12 weeks, of which venous blood samples were collected 14 d after treatment with cinaeiguat, and determined for glucose and lipid contents by full-automatic biochemical analyzer, for superoxide dismutase （SOD） activity and malonaldehyde （MDA） content by colorimetry, and for endothelin （ET-1） content by ELISA. Results Compare with that in model group, the blood glucose levels of rats treated with cinacignat at low, moderate and high doses showed no significant decrease （each P 〉 0. 05 ）, while the trig｜yceride （TG） and cholesterol （TC） contents decreased significantly （each P 〈 0. 05 ）, the SOD activity increased significantly, and the MDA and ET-1 contents decreased significantly. Conclusion Cinaciguat might regulate the blood lipid content, decrease the oxidative stress level and improved the function of vascular endothelial cells.