改变血红素加氧酶-1水平对糖尿病大鼠氧化应激状态及肾功能的影响

Effect of heme oxygenase-1 on oxidative stress and renal function in diabetic rats

目的探讨血红素加氧酶-1(HO-1)对糖尿病(DM)大鼠氧化应激状态及肾功能的影响。方法以链脲佐菌素诱导DM大鼠模型。SD大鼠分成4组:对照组、DM组、正铁血红素Hemin(HO-1)诱导剂组、ZnPP(HO-1抑制剂)组。检测血清总抗氧化能力(TAOC)、丙二醛(MDA)含量和尿白蛋白排泄率(UEA);RT-PCR法检测肾脏组织TNF-α和HO-1mRNA表达水平。结果 Hemin组血清总抗氧化能力与DM组相比明显增高;而给予ZnPP后DM大鼠MDA含量增加,总抗氧化能力降低;DM大鼠UEA上升(P均<0.01),并随病程延长而加重。Hemin组UEA与DM5 w组相比已有下降趋势,但尚无统计学差异(P>0.05);ZnPP组大鼠UEA明显增高(P<0.01);与对照组相比,DM大鼠肾组织TNF-α及HO-1 mRNA表达增加;应用Hemin后DM大鼠肾脏组织TNF-α表达减少(P<0.01)。结论提高DM大鼠肾脏HO-1表达水平可以改善肾组织氧化应激状态、延缓肾功能障碍。

Objective To explore the effect of heme oxygenase-1（HO-1）and its anti-oxidant capacity in diabetic nephropathy.Methods Rats were divided into control,diabetes mellitus（DM）,Hemin（HO-1 inducer） and ZnPP（HO-1 inhibitor） groups.Serum total antioxidant capacities（T-AOC） and malondialdehyde（MDA） contents were detected.Urinary albumin excretion（UEA） was also observed.Expression of HO-1 and TNF-α in renal tissue were examined by RT-PCR.Results Serum TAOC of DM rats was decreased in a time-dependent manner,while the content of MDA and UEA was progressively increased.After pretreatment with Hemin for 5 weeks in DM rats,T-AOC was higher than that of DM group.Alternatively,pretreatment with ZnPP in DM rats,a lower level of T-AOC and a higher content of MDA and UEA were measured.Upregulated TNF-α and HO-1 mRNA expression in renal tissue from DM rats were observed when compared with those of control group detected by RT-PCR,while TNF-α expression was reduced after treatment with Hemin.Conclusions Upregulation of HO-1 may increase the antioxidant capacities of renal tissue and ameliorate the dysfunction in diabetes.