CAJ | 학술논문

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(n=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).每周称景大鼠体重,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索和胰岛索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.
목적 탐토록사탄여필격렬동련용대대사종합정대서신장보호작용급가능궤리.방법 웅성SD대서39지,괄응성위양1주후,수궤추취7지위정상대조조(표위A조)용보통사료가자래수위양,령32지용고염고지화20%자당수위양,재제8주,장25지조모성공적대서수궤분위4조:B조위모형조(n=7),C조위록사탄치료조(20mg/kg,n=6),D조위필격렬동치료조(10mg/kg)(n=6),E조위록사탄화필격렬동연합치료조(삼조단치료조제량,n=6).매주칭경대서체중,혈압매월측량일차,재0,8,16주후수집24소시뇨액.우16주말처사대서수취혈액표본병수집내장지방칭중,적취신장표본주병리화VEGF면역조직화학검측.결과 각치료조화모형조상비혈압、혈청담고순、감유삼지농도급뇨백단백량강저(P<0.05);재필격렬동급연합용약조혈청이도색화이도색저항지수여모형조상비명현강저(p<0.05);모형조대서신장중VEGF표체여정상조비명현강저(p<0.05),단경치료후각조여모형조상비변화무통계학의의(p>0.05).결론 대사종합정대서신손해가능여신장조직중표체VEGF하강유관;록사탄여필격렬동련용가강압,감소뇨백단백,증가이도소민감,종일정정도상기도신장보호적작용,단무명현증가신장조직중VEGF표체작용.
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 ( Egroup, 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. 0S ) but not significantly increased treated with any therapy(p >0. 05). In Piogligtanzone and combined group the serum insulin and the HOMA-R 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.