CAJ | 학술논문

目的：进一步明确替米沙坦治疗糖尿病肾病的机制,探讨过氧化物酶体增殖物激活受体γ( PPARγ)通路在其中的作用。方法构建糖尿病肾病大鼠模型,将其随机分为空白对照组、替米沙坦组(5 mg·kg-1·d-1)、替米沙坦联合PPARγ抑制剂治疗组(替米沙坦5 mg·kg-1·d-1；GW96620.5 mg·kg-1·d-1),治疗12周后检测并比较3组SD大鼠的血、尿生化指标及肾脏质量,ELISA法检测并比较3组SD大鼠血液中白细胞介素_1( IL_1)、白细胞介素_6( IL_6)、肿瘤坏死因子_α( TNF_α)的表达水平,比较分析各组肾脏组织病理变化。 Western_blot或免疫组化法检测并比较3组SD大鼠肾脏组织HGF的表达,以及活化的NF_κB(P65)的水平。结果替米沙坦能够显著改善糖尿病肾病大鼠的血、尿生化指标,减轻肾脏质量,缩小肾小球体积,减轻系膜增生,减少炎性细胞浸润；明显降低血液中IL_1、IL_6、TNF_α表达水平,及肾脏组织中活化的NF_κB(P65)的水平,增加肾脏组织中HGF表达。但以上变化能被PPARγ抑制剂GW9662有效逆转。结论 PPARγ相关通路活化可能在替米沙坦治疗糖尿病肾病中起重要作用。
목적：진일보명학체미사탄치료당뇨병신병적궤제,탐토과양화물매체증식물격활수체γ( PPARγ)통로재기중적작용。방법구건당뇨병신병대서모형,장기수궤분위공백대조조、체미사탄조(5 mg·kg-1·d-1)、체미사탄연합PPARγ억제제치료조(체미사탄5 mg·kg-1·d-1；GW96620.5 mg·kg-1·d-1),치료12주후검측병비교3조SD대서적혈、뇨생화지표급신장질량,ELISA법검측병비교3조SD대서혈액중백세포개소_1( IL_1)、백세포개소_6( IL_6)、종류배사인자_α( TNF_α)적표체수평,비교분석각조신장조직병리변화。 Western_blot혹면역조화법검측병비교3조SD대서신장조직HGF적표체,이급활화적NF_κB(P65)적수평。결과체미사탄능구현저개선당뇨병신병대서적혈、뇨생화지표,감경신장질량,축소신소구체적,감경계막증생,감소염성세포침윤；명현강저혈액중IL_1、IL_6、TNF_α표체수평,급신장조직중활화적NF_κB(P65)적수평,증가신장조직중HGF표체。단이상변화능피PPARγ억제제GW9662유효역전。결론 PPARγ상관통로활화가능재체미사탄치료당뇨병신병중기중요작용。
Objective To demonstrate the mechanisms underlying the efficacy of telmisartan in diabetic nePhroPathy, and discuss the role of PPARγin this Process. Methods The diabetic nePhroPathy rat models were established and randomly assigned to control grouP, telmisartan grouP ( 5 mg · kg-1 · d-1 ) and combination of telmisartan and PPARγ inhibitor grouP (telmisartan:5 mg·kg-1·d-1;GW9662:0. 5 mg·kg-1·d-1). After 12 weeks of treatment,the biochemical indexes of blood and urine,kidney weight,renal Pathology in each grouP of diabetic nePhroPathy rats were measured and comPared. The leVels of IL_1,IL_6 and TNF_α in blood of each grouP were detected by ELISA and comPared. The leVels of HGF and actiVated NF_κB (P65) in renal tissue of each grouP were detected by Western blotting and comPared. Results In diabetic nePhroPathy rats, telmisartan lowered the leVels of serum glucose, serum creatinine, urinary Protein and kidney weight, decreased the glomerular Volume,mesangial Proliferation and inflammatory cell infiltration,reduced blood leVels of IL_1,IL_6,and TNF_α,and decreased leVel of actiVated NF_κB (P65) in renal tissue. The leVel of HGF in renal tissue was eleVated by telmisartan. NeVertheless,these changes were Partly reVersed by PPARγ inhibitor GW9662. Conclusion PPARγ Presents an imPortant role in treatment of diabetic nePhroPathy by telmisartan.