目的探讨血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂（ARB）对2型糖尿病肾病（DN）大鼠肾小球内12．脂氧合酶（12-LO）活性及P钙黏蛋白（P．cadherin）表达的影响。方法用10^-7 mol／L Ang II处理足细胞24h。采用皮下包埋的微型渗透泵给雄性S...目的探讨血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂（ARB）对2型糖尿病肾病（DN）大鼠肾小球内12．脂氧合酶（12-LO）活性及P钙黏蛋白（P．cadherin）表达的影响。方法用10^-7 mol／L Ang II处理足细胞24h。采用皮下包埋的微型渗透泵给雄性SD大鼠分别持续恒速注入12-LO代谢产物12羟二十烷四烯酸[12（S）-HETE，1mg·kg-1·d-1]和AngⅡ（400ng·kg-1·min-1）1周和2周。使用高脂饮食结合小剂量链脲菌素（STZ）诱导2型糖尿病模型，大鼠模型成功后随机分为2组：DN组和ARB（5mg·kg-1·d-1洛沙坦）组。以规律正常饮食大鼠作为对照组。6周后处死大鼠，收集尿、血液，提取肾脏，用系列过筛方法分离肾小球。采用ELISA、RT-PCR和Western印迹法分别检测相关指标。结果Ang II的直接刺激可以诱导足细胞及肾小球内12（s）．HETE含量增高（P〈0．01）。12（S）-HETE刺激使大鼠肾小球内AngII含量增高（P〈0．01）。与对照组比较，DN组血糖（P〈0．01）、肾质量／体质量（P〈0．01）和24h尿白蛋白明显增高（P〈0．01），但洛沙坦治疗后尿白蛋白（P〈0．05）、肾质量／体质量（P〈0．05）明显低于DN组。与对照组比较，DN组肾小球内12（s）．HETE含量明显增高（P〈0．01），P．cadherinmRNA和蛋白表达明显降低（P〈0．01），但洛沙坦治疗后肾小球内12（s）-HETE含量明显低于DN组（P〈0．05），P—cadherinmRNA和蛋白表达明显高于DN组（P〈0．05）。结论AngII通过激活12-LO诱导肾小球内P．cadherin的表达下调。ARB通过抑制12-LO活性而上调DN肾小球内P—cadherin表达，从而延缓DN的进展。展开更多
Recent studies suggest that treatment with angiotensin Ⅱ type 1 (AT1) receptor blockers and lipid lowering agents, namely the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins may have ...Recent studies suggest that treatment with angiotensin Ⅱ type 1 (AT1) receptor blockers and lipid lowering agents, namely the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins may have beneficial effects on renal function independent of lowering actions on blood pressure and cholesterol.^(1,2) However, the renal effects of the combination of AT1 receptor blockers and statins in experimental diabetes are unknown. The aims of the present study were to determine whether valsartan and fluvastatin would lower the expression of nuclear factor kappa B ((NF-κB))and monocyte chemoattractant protein (MCP-1) in the tubulointerstitium and improve renal function and to see whether treatment with a combination of valsartan and fluvastatin would have any extra beneficial effect in streptozotocin (STZ)-induced unilaterally nephrectomized diabetic rats.展开更多
文摘目的探讨血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂（ARB）对2型糖尿病肾病（DN）大鼠肾小球内12．脂氧合酶（12-LO）活性及P钙黏蛋白（P．cadherin）表达的影响。方法用10^-7 mol／L Ang II处理足细胞24h。采用皮下包埋的微型渗透泵给雄性SD大鼠分别持续恒速注入12-LO代谢产物12羟二十烷四烯酸[12（S）-HETE，1mg·kg-1·d-1]和AngⅡ（400ng·kg-1·min-1）1周和2周。使用高脂饮食结合小剂量链脲菌素（STZ）诱导2型糖尿病模型，大鼠模型成功后随机分为2组：DN组和ARB（5mg·kg-1·d-1洛沙坦）组。以规律正常饮食大鼠作为对照组。6周后处死大鼠，收集尿、血液，提取肾脏，用系列过筛方法分离肾小球。采用ELISA、RT-PCR和Western印迹法分别检测相关指标。结果Ang II的直接刺激可以诱导足细胞及肾小球内12（s）．HETE含量增高（P〈0．01）。12（S）-HETE刺激使大鼠肾小球内AngII含量增高（P〈0．01）。与对照组比较，DN组血糖（P〈0．01）、肾质量／体质量（P〈0．01）和24h尿白蛋白明显增高（P〈0．01），但洛沙坦治疗后尿白蛋白（P〈0．05）、肾质量／体质量（P〈0．05）明显低于DN组。与对照组比较，DN组肾小球内12（s）．HETE含量明显增高（P〈0．01），P．cadherinmRNA和蛋白表达明显降低（P〈0．01），但洛沙坦治疗后肾小球内12（s）-HETE含量明显低于DN组（P〈0．05），P—cadherinmRNA和蛋白表达明显高于DN组（P〈0．05）。结论AngII通过激活12-LO诱导肾小球内P．cadherin的表达下调。ARB通过抑制12-LO活性而上调DN肾小球内P—cadherin表达，从而延缓DN的进展。
文摘Recent studies suggest that treatment with angiotensin Ⅱ type 1 (AT1) receptor blockers and lipid lowering agents, namely the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins may have beneficial effects on renal function independent of lowering actions on blood pressure and cholesterol.^(1,2) However, the renal effects of the combination of AT1 receptor blockers and statins in experimental diabetes are unknown. The aims of the present study were to determine whether valsartan and fluvastatin would lower the expression of nuclear factor kappa B ((NF-κB))and monocyte chemoattractant protein (MCP-1) in the tubulointerstitium and improve renal function and to see whether treatment with a combination of valsartan and fluvastatin would have any extra beneficial effect in streptozotocin (STZ)-induced unilaterally nephrectomized diabetic rats.
