厄贝沙坦联合格列齐特对2型糖尿病大鼠肾功能的保护作用与机制  

Protective Effect of Irbesartan and Gliclazide on Renal Function in Type 2 Diabetic Rats

作　　者：兰海涛[1] 刘红[1] 买文丽[1] 刘行海[1] 刘华[1] 郑倩[1] 

机构地区：[1]川北医学院生理学教研室,南充637000

出　　处：《成都医学院学报》2013年第5期544-547,574,共5页Journal of Chengdu Medical College

基　　金：四川省教育厅重点项目(NO:2010ZA169);四川省教育厅青年基金项目(NO:2009ZB122)

摘　　要：目的研究厄贝沙坦联合格列齐特对2型糖尿病(T2DM)大鼠肾功能的保护作用与机制。方法建立T2DM大鼠模型后,分别给予格列齐特、厄贝沙坦联合格列齐特灌胃治疗,定期检测大鼠血糖、血脂、血清胰岛素(FINS)、肌酐(Cr)、尿素氮(BUN)、尾动脉收缩压(SBP)、肾脏肥大指数和肾皮质钠泵活性等指标。结果 1)与正常对照组比较,8w和16w时模型大鼠胰岛素敏感指数(ISI)和肾皮质钠泵活性都显著降低,血糖、血脂、SBP、Cr和BUN都显著升高(P<0.01),16w时肾脏肥大指数显著升高(P<0.01)。2)与模型对照组比较,格列齐特治疗组和厄贝沙坦联合格列齐特治疗组大鼠血糖、血脂、Cr和BUN都显著降低,ISI和肾皮质钠泵活性都显著升高,16w时肾脏肥大指数也显著降低(P<0.01)。3)与格列齐特治疗组比较,厄贝沙坦联合格列齐特治疗组大鼠尾动脉SBP、Cr和BUN都显著降低,ISI和肾皮质钠泵活性显著升高,16w时大鼠的肾脏肥大指数也显著降低(P<0.01),其余指标比较差异无统计学意义(P>0.05)。4)厄贝沙坦联合格列齐特治疗8w和16w组间比较,除16w时BUN显著降低外,其余指标差异无统计学意义(P>0.05)。结论厄贝沙坦联合格列齐特比单独使用格列齐特治疗T2DM大鼠,能更有效保护大鼠肾功能,其机制可能与格列齐特降低大鼠血糖、血脂,同时厄贝沙坦抑制肾脏局部肾素-血管紧张素系统(RAS)的作用有关。Objective To investigate the effect and mechanism of irbesartarl and glielazide on renal fuction in type 2 diabetic rats. Methods Female Wistar rats were treated with STZ to develop a rat model of type 2 diabetes mellitus （T2DM）. Rats were treated with gliclazide or irbesartan and glielazide for 8 weeks or 16 weeks. Serum biochemistry was performed. Results 1） Compared with normal control group, insulin sensitivity index （ISI） and sodium pump activity of renal cortex in the model control group were significant decreased, but blood sugar, blood lipids, blood pressure, serum creatinine and urea nitrogen were significant increased, kidney hypertrophy index was significantly increased on 16th week （P（0.01）. 2）Compared with model control group, blood sugar, blood lipid, serum creatinine,urea nitrogen and blood pressure of tail artery were decreased （P（0.01）, ISI and sodium pump activity of renal cortex were significant increased in gliclazide group and irhesartan combined with glidazide treated rats （P〈0. 01）. KW/BW was significant decreased on the 16th week （P〈0. 01）. 3） Compared with gliclazide treatment group,blood pressure,blood creatinine and urea were significantly decreased, ISI and renal sodium pump activity was significantly increased in the irbesartan combined with gliclazide treatment group rat, KW/BW was significant decreased on 16th week （P〈0.01）, there was no significant difference between the other index （P〉0.05）. 4）In rats treated with irbesartan and glielazide, the urea nitrogen was significant decreased in 16th week as compared to the 8th week,and there was no significant difference in other indexes （P〉0.05）. Conclusion Gliclazide and irbesartan can protect against renal function in type 2 diabetic rats, and the protection may he related to the decrease of blood sugar and blood lipid, stable sodium pump activity of renal cortex, and the inhibition of the rennin- angiotensin system.

关 键 词：厄贝沙坦 格列齐特 2型糖尿病 肾功能 钠泵 肾素-血管紧张素系统 

分 类 号：R285.5[医药卫生—中药学]