摘要
目的探讨氯沙坦与吡格列酮联用对代谢综合征大鼠肾脏保护作用及可能机理。方法雄性sD大鼠39只，适应性喂养1周后，随机抽取7只为正常对照组（标为A组）用普通饲料加自来水喂养，另32只用高盐高脂和20％蔗糖水喂养，在第8周，将25只造模成功的大鼠随机分为4组：B组为模型组（13=7），C组为氯沙坦治疗组（20mg／kg，n=6），D组为吡格列酮治疗组（10mg／kg）（n=6），E组为氯沙坦和吡格列酮联合治疗组（参照单治疗组剂量，n=6）。每周称量大鼠体重，血压每月测量一次，在0，8，16周后收集24小时尿液。于16周末处死大鼠收取血液标本并收集内脏脂肪称重，摘取肾脏标本做病理和VEGF免疫组织化学检测。结果各治疗组和模型组相比血压、血清胆固醇、甘油三酯浓度及尿白蛋白量降低（P〈0．05）；在吡格列酮及联合用药组血清胰岛素和胰岛素抵抗指数与模型组相比明显降低（P〈0．05）；模型组大鼠肾脏中VEGF表达与正常组比明显降低（P〈0．05），但经治疗后各组与模型组相比变化无统计学意义（p〉0．05）。结论代谢综合征大鼠肾损害可能与肾脏组织中表达VEGF下降有关；氯沙坦与吡格列酮联用可降压，减少尿白蛋白，增加胰岛素敏感，从一定程度上起到肾脏保护的作用，但无明显增加肾脏组织中VEGF表达作用。
Objectives To evaluated the effects and its possible mechanism of Losartan and Pioglitanzone combined with metabolic syndrome rats. Methods 39 male Sprague - Dawley （SD） rats were acclimatized to experimental environment for one week, then 7 rats were randomly separated as control group （A group, n = 7 ） which fed with normal diet and tap water, others fed with high - fat,high - salt diet and 20% sucrose solution, at 8 weeks, the successful models were randomly divided four groups： metabolic syndrome model group（ B group, n = 7 ）, Losartan treatment group （ C group,20mg/kg, n = 6）, Pioglitanzone group（ D group, 10mg/kg） and combined group（ E group, treated with Lostartan and Pioglitanzone combined at the above dosage）. During the entire period of the experiment, body weight was measured weekly. The rats were placed in metabolic cages to collect 24 h urine at the 0 week, 8 weeks and end of this study. Systolic blood pressure（SBP） was measured monthly. At 16 weeks, the rats were all killed. Blood samples were drawn from abdominal aorta, centrifuged to obtain serum. Kidneys were removed, decapsulated and immediately weighed. Visceral fat mass （ mesenteric, epididymal and retroperitoneal adipose tissue） was excised and weighed. The kidney specimens were taken for the pathology and the immuohistochemistry of VEGF. Results SBP, total cholesterol, triglycerides and urine albumin excretion of the treatment groups were significantly decreased compared with model group （ p 〈 0. 05 ）, the expression of VEGF in model group was significantly decreased compared with control group（ p 〈0.05 ） but not significantly increased treated with any therapy（ p 〉 0.05 ）. In Piogligtanzone and combined group the serum insulin and the HOMA -IR were decreased vs. model group（ p 〈 0.05 ）. Conclusions Kidney dysfunction of metabolic syndrome is closely related to the decrease of expression of VEGF;the combined treatment with Losartan and pioglitanzone can protect kidney through decrease systolic blood pressure, urinary albumin excretion and increase insulin sensitive, but not increase expression of VEGF in kidney tissue of metabolic syndrome rats.
出处
《国际泌尿系统杂志》
2011年第4期436-440,共5页
International Journal of Urology and Nephrology
关键词
代谢疾病
综合征
大鼠
洛沙坦
噻唑类
Metabolic Diseases
Syndrome
Rats
Losartan
Thiazoles
