目的 探讨血管紧张素-(1-7)/血管紧张素-Ⅱ[Ang-(1-7)/Ang-Ⅱ]调节NF-E2-related factor-2(Nrf2)/血红素氧合酶1(HO-1)通路在糖尿病肾脏缺血再灌注损伤中的作用及机制.方法 60只成年雄性SD大鼠随机分为正常假手术组(Sham组)、正常缺血再灌注组(IR组)、糖尿病假手术组(DS组)、糖尿病缺血再灌注组(DIR组),每组各15只.检测血尿素氮(BUN)、肌酐(Cr)和中性粒细胞明胶酶相关载脂蛋白(NGAL),观察肾脏病理学改变,检测肾组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,Western blot检测Ang-(1-7)和Ang-Ⅱ蛋白以及Nrf2和HO-1蛋白表达.结果 Ang-(1-7)蛋白在DS组中表达较Sham组增加(P＜0.05),在IR组中表达较Sham组减少(P＜0.05),而在DIR组中较IR组进一步减少(P＜0.05).IR组和DS组中Ang-Ⅱ蛋白表达显著高于Sham组(P＜0.05),而DIR组中Ang-Ⅱ蛋白表达进一步增高(P＜0.05).IR组和DS组中Nrf2和HO-1蛋白表达显著高于Sham组(P＜0.05),而DIR组中Nrf2和HO-1蛋白表达较IR组和DS组降低(P＜0.05).与Sham组比较,IR组和DS组中肾脏损伤程度显著增高(P＜0.05),血清BUN、Cr和NGAL水平、肾脏组织MDA含量明显升高而SOD活性显著降低(P＜0.05).与IR组和DS组比较,DIR组中肾脏损伤程度进一步增高(P＜0.05),血清BUN、Cr和NGAL水平、肾脏组织MDA含量明显增高,而SOD活性明显降低(P＜0.05).结论 缺血再灌注可能通过抑制Ang-(1-7),激活Ang-Ⅱ,下调Nrf2/HO-1通路的抗氧化应激能力,加重了糖尿病肾脏的损伤.%Objective To investigate the role of angiotensin-(1-7)/angiotensin-Ⅱ [Ang-(1-7)/Ang-Ⅱ] in kidney ischemia-reperfusion injury by regulating NF-E2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in diabetic rats.Methods Sixty male SD rats were randomly divided into four groups:Sham group,kidney ischemia-reperfusion group (IR group),diabetic group (DS group),diabetic+KIR group (DIR group),with 15 rats in each group.Kidney ischemia reperfusion model of STZ-diabetic rat model was used.After 24h reperfusion,blood urea nitrogen (BUN),creatinine (Cr),and neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were measured.Renal histology was observed and evaluated.Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in renal tissues were detected.Western blot were used to observe the expression levels of Ang-(1-7),Ang-Ⅱ and Nrf2,HO-1 in renal tissues.Results Expressions of Ang-(1-7) in DS group were higher than those in sham group (P ＜ 0.05),the expressions of Ang-(1-7) in IR group were lower than those in sham group (P ＜ 0.05),the expressions of Ang-(1-7) in DIR group were much lower than those in IR group (P ＜ 0.05).The expressions of Ang-Ⅱ in IR and DS group were higher than those in Sham group (P ＜ 0.05),the expressions of Ang-Ⅱ in DIR group were higher than those in IR and DS group (P ＜ 0.05).The expressions of Nrf2 and HO-1 in IR and DS group were higher than those in sham group (P ＜ 0.05),the expressions of Nrf2 and HO-1 in DIR group were lower than those in IR and DS group (P ＜ 0.05).Compare with Sham group,BUN,Cr and NGAL in serum and MDA levels in the renal tissues were increased,and SOD levels were decreased in IR and DS group (P ＜ 0.05).Compare with IR and DS group,BUN,Cr and NGAL in serum and MDA levels in the renal tissues were further increased (P ＜ 0.05),and SOD levels were further decreased in DIR group (P ＜ 0.05).Conclusion Ischemia reperfusion might inhibit the Ang-(1-7),activate the Ang-Ⅱ and down regulate the anti-oxidative stress of Nrf2/HO-1 pathway,resulting in the damage of diabetic kidney.
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