摘要
目的通过观察胰高血糖素样肽-1(GLP-1)类似物利拉鲁肽对2型糖尿病大鼠肾脏内髓一氧化氮合酶(NOS)、环加氧酶2(COX2)表达的影响,探讨利拉鲁肽降血压和利水盐的作用机制。方法 30只雄性SD大鼠给予高糖高脂饲料喂养,自由摄水,8周后空腹注射链脲佐菌素(STZ),成功建立2型糖尿病大鼠模型18只,选取12只随机分为利拉鲁肽处理2型糖尿病模型(DMT)组和2型糖尿病模型(DM)组,另取12只正常大鼠随机分为利拉鲁肽处理野生型大鼠(WTT)组和野生型大鼠对照(WT)组,每组6只。DMT和WTT组每天予以利拉鲁肽(200μg/kg体质量)皮下注射,DM和WT组每天予以等量生理盐水皮下注射,各组分别在给药后0、2、4、6周检测血糖和血压,给药后6周收集尿液检测K、Na、Cl离子浓度,然后处死大鼠,收集血液检测血K、Na、Cl离子浓度,取肾组织通过Real-timePCR和Western blot检测肾脏内髓NOS和COX2的m RNA和蛋白表达水平。结果利拉鲁肽干预后,DMT组大鼠血糖(F=5.933,P<0.05)及血压(F=22.070,P<0.05)随时间变化逐渐降低。在干预6周后,DMT组大鼠血糖(mmol/L:12.78±3.82 vs.18.75±1.68)和血压(mm Hg:119.98±4.43 vs.136.42±4.48)较DM组均明显降低(P<0.05),血液中K、Na、Cl离子浓度与DM组相比无明显差异,但尿液中K(mmol/L:46.55±6.43 vs.33.13±9.71)、Na(mmol/L:56.33±8.83vs.41.20±7.25)、Cl(mmol/L:159.81±25.06 vs.71.44±12.99)离子浓度高于DM组大鼠(P<0.05),且肾脏内髓NOS、COX2的m RNA和蛋白表达均高于DM组大鼠(P<0.05)。结论利拉鲁肽可能通过NOS诱导COX2的表达增强,发挥利水盐、降血压的作用。
Objective To observe the effects of glucagon like peptide-1 (GLP-1) analogues liraglutide on expressions of nitric oxide synthase (NOS) and cyclo-oxygen-ase (COX)2 in renal medulla of type 2 diabetes rats, and the mechanism of its lowering blood pressure and promoting excretion of water and salt in kidney. Methods Type 2 diabetes model rats were generated by high-fat and high-sugar feeding for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ). Subse?quently, eighteen type 2 diabetes rats were divided into two groups: liraglutide treatment group (DMT) and diabetes group (DM). Twelve normal rats were divided into two groups: liraglutide treatment wild type group (WTT) and wild type group (WT). DMT and WTT groups were given liraglutide (200μg/kg) by subcutaneous injection, DM and WT groups were given equivalent normal saline by the same way. The levels of blood glucose and blood pressure were detected at 0, 2, 4 and 6 weeks after treatment in groups of rats. Samples of urine were collected for detecting ion concentrations (K+, Na+and Cl-) af?ter treatment for six weeks. Rats were sacrificed and blood samples were collected for detecting ion concentrations (K+, Na+and Cl-). The expression levels of NOS and COX2 mRNA and protein in renal medulla were detected by real-time PCR and Western blot assay. Results After treating with liraglutide, the values of blood glucose (F=5.933, P<0.05) and blood pres? <br> sure (F=22.070, P<0.05) were gradually decreased in DMT group. After treatment with liraglutide for 6 weeks, the values of blood glucose (mmol/L:12.78 ± 3.82 vs. 18.75 ± 1.68) and blood pressure (mmHg:119.98 ± 4.43 vs. 136.42 ± 4.48) were signifi?cantly decreased (P<0.05) in DMT group than those of DM group (P<0.05). There were no significant differences in the concentrations of K+, Na+and Cl-between the two groups. There were higher levels of K+(mmol/L:46.55 ± 6.43 vs. 33.13 ± 9.71), Na+(mmol/L:56.33±8.83 vs. 41.20±7.25) and Cl-(mmol/L:159.81±25.06 vs. 71.44±12.99) in urine in DMT group than those of DM group (P<0.05). The mRNA levels and protein expressions of NOS and COX2 in renal medulla were significant?ly increased in DMT group than those of DM group (P<0.05). Conclusion GLP-1 analogues liraglutide may enhance the expression of COX2 by increasing the expression of NOS to excrete water and salt, and decrease blood pressure.
出处
《天津医药》
CAS
2016年第7期849-853,共5页
Tianjin Medical Journal
基金
四川省教育厅2013年科研资助重点项目(13ZA0213)
四川省卫生厅2013年科研资助项目(130386)
成都医学院驼鸟计划2012年专项基金资助项目(CYX12-024)
2014校级大学生创新实验计划项目(CXXS201422)
