摘要
目的研究1型糖尿病大鼠早期肾脏皮质血管紧张素原(angiotensinogen,AGT)表达的改变以及抗氧化应激干预对其表达的影响,分析肾素-血管紧张素系统(renin-angiotensin system,RAS)与氧化应激作用的关系。方法将正常雄性SD大鼠随机分为两组,糖尿病(diabetes mellitus,DM)大鼠组腹腔注射链脲佐菌素(streptozotocin,STZ)造1型糖尿病大鼠模型,需鉴定其成模,非糖尿病(Non-DM)大鼠组腹腔注射同等剂量的载体溶剂(1 ml/100 g),观察至4周末;对比2组大鼠体质量、血糖水平、血压水平及肾脏皮质AGT的表达水平。分别选用氯沙坦、肼屈嗪以及氧化应激反应拮抗剂作为干预手段,对成模后的DM大鼠进行干预,持续至4周末,与阳性对照组相比,对比各干预组糖尿病大鼠体质量、血糖水平、血压水平及肾脏皮质AGT的表达水平。结果与Non-DM组大鼠比较,4周末DM大鼠体质量、血糖水平均有显著性差异(P<0.05),而血压水平无显著性差异(P>0.05);肾脏皮质AGT表达水平显著升高(P<0.05);与阳性对照组比较,4周末各干预组大鼠体质量、血糖水平、血压水平均无显著性差异(P>0.05);氯沙坦和氯化应激反应拮抗剂组肾脏皮质AGT的表达有所下调(P<0.05),肼屈嗪组AGT表达没有显著改变(P>0.05)。结论 1型糖尿病大鼠早期肾脏皮质AGT表达有所上调,抗氧化应激干预与RAS受体阻断剂干预均能降低AGT的表达水平,这说明RAS和氧化应激作用有一定的关联性。
Objective To observe the changes of kidney cortex angiotensinogen(AGT)expression in rate typeⅠ diabetes model,and the effect of the anti-oxidative stress induction on the kidney cortex AGT expression in order to infer indirectly that there is some relationship between renin-angiotensin system(RAS)and oxidative stress.Methods First part of the experiment:Male Sprague Dawley(SD)rats were randomly divided into two groups:diabetic mellitus(DM)group and non-DM group.Rats in DM group were injected with streptozotocin(STZ)intraperitoneally,and those in nonDM group were given the same dosage of vehicle.The body weight,blood glucose,blood pressure and AGT expression in both groups were measured at the end of 4 weeks.Second part of the experiment:All typeⅠ diabetes rats were randomly divided into four groups,and administrated with distilled water,Losartan,hydralazine and Tempol respectively.The body weight,blood glucose,blood pressure and AGT expression in all groups were detected after 4 weeks since the typeⅠ diabetes model was established.Results There were significant differences in body weight,blood glucose and blood pressure between non-DM group and DM group after 4 weeks(P〈0.05).The cortex AGT expression was up-regulated in DM group.There was no significant difference in body weight,blood glucose and blood pressure among the four groups.The cortex AGT expression in Losartan group and Tempol group was reduced significantly,and that in hydralazine group had no changes as compared with the distilled water group.Conclusions The cortex AGT expression was up-regulated in DM group.Both anti oxidative stress and Losartan can reduce the AGT expression,suggesting some relationships between the activity of RAS and oxidative stress.
作者
郑伟平
梁翔
邹原方
刘玉峰
苏晓燕
ZHENG Wei-ping LIANG Xiang ZOU Yuan-fang LIU Yu-feng SU Xiao-yan(Donghua Hospital, Sun Yat-sen University, Dongguan 523110, China)
出处
《临床肾脏病杂志》
2017年第5期303-307,共5页
Journal Of Clinical Nephrology
基金
广东省医学科学技术研究基金面上项目(No.20161122099434)