血红素氧合酶-1在感染性休克大鼠肾功能损伤中的作用

目的 探讨血红素氧合酶-1(HO-1)在感染性休克大鼠肾功能损伤中的作用.方法 健康清洁级SD大鼠80只,月龄3～4月,体重260～330 g,雌雄不拘,随机分为4组(n=20):对照组(C组)、感染性休克组(S组)、感染性休克+ZnPP-Ⅸ组(SZ组)和ZnPP-Ⅸ组(Z组).C组静脉注射生理盐水0.5 ml,2 h后腹腔注射50 mmol/L碳酸氢钠溶液1 ml;S组静脉注射LPS 10 mg/kg,2 h后腹腔注射50 mmol/L碳酸氢钠溶液1 ml;SZ组静脉注射LPS 10 mg/kg,2 h后腹腔注射ZnPP-Ⅸ10 μmol/kg;Z组静脉注射生理盐水0.5 ml,2 h后腹腔注射ZnPP-Ⅸ10 μmol/kg.于腹腔注射碳酸氢钠溶液或ZnPP-Ⅸ后4 h时,检测碳氧血红蛋白浓度(COHb)、血清尿素氮(BUN)、肌酐(Cr)的浓度和尿α1-微球蛋白(α1-M)浓度、N-乙酰-a-D-氨基葡萄糖酐酶(NAG)活性、视黄醇结合蛋白(RBP)浓度、γ-谷氨酰转肽酶(γ-GT)活性、肾组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、HO-1 mRNA、HO-2 mRNA、HO-1和HO-2的表达水平.结果 与C组比较,S组和SZ组血清Cr、BUN的浓度、尿α1-M、RBP、NAG、γ-GT水平、COHb、肾组织MDA、HO-1 mRNA、HO-1水平升高,肾组织SOD活性降低(P<0.05),Z组上述指标差异无统计学意义(P>0.05);与S组比较,SZ组血清Cr、BUN的浓度、尿α1-M、RBP、NAG、γ-GT水平和肾组织MDA含量升高,肾组织SOD活性、COHb和肾组织HO-1 mRNA、HO-1水平降低(P<0.05);4组大鼠肾组织HO-2 mRNA、HO-2表达差异无统计学意义(P>0.05).结论 肾组织HO-1对感染性休克大鼠的肾功能可产生一定的保护作用.

Role of heine oxygenase-1 in renal function injury during septic shock in rats

Objective To investigate the role of heme oxygenase-1 (HO-1) in renal function injury during septic shock in rats.Methods Eighty healthy SD rats of both sexes,aged 3-4 months,weighing 260-330 g,were randomly divided into 4 groups ( n = 20 each) : control group ( group C),septic shock group ( group S),S + ZnPP-Ⅸ group (group SZ) and ZnPP-Ⅸ group (group Z).Group C received iv normal saline 0.5 ml and 2 h later,received intraperitoneal 50 mmol/L sodium bicarbonate 1 ml.Group S received iv LPS 10 mg/kg and 2 h later,received intraperitoneal 50 mmol/L sodium bicarbonate 1 ml.Group SZ received iv LPS 10 mg/kg and 2 h later,received intraperitoneal ZnPP-Ⅸ 10 μmol/kg.Group Z received iv normal saline 0.5 ml and 2 h later,received by intraperitoneal ZnPP-Ⅸ 10 μmol/kg.Carboxyhemoglobin concentration (COHb),concentrations of serum urea nitrogen (BUN) and creatinine (Cr),urinary α1 -microglobulin ( α1 -M) concentration,N-acetyl-beta-D-glucosamidase (NAG) activity,retinol binding protein (RBP) concentration and γ-glutamyl transpeptidase (γ-GT) activity,MDA content,SOD activity and expression of HO-1 mRNA,HO-2 mRNA,HO-1 and HO-2 in renal tissue were detected at 4 h after administration of sodium bicarbonate or ZnPP-Ⅸ.Results The concentrations of serum BUN and Cr,urinary α1-M concentration,NAG activity,RBP concentration and γ-GT activity,COHb,MDA content,expression of HO-1 mRNA and HO-1 in renal tissue were significantly higher and SOD activity lower in group S and SZ than in group C ( P < 0.05),while there were no significant difference in the above parameters between group Z and C ( P > 0.05).The concentrations of serum BUN and Cr,urinary α1-M concentration,NAG activity,RBP concentration and γ-GT activity,and MDA content in renal tissue were significantly higher,while SOD activity,COHb,and expression of HO-1 mRNA and HO-1 lower in group SZ than in group S ( P < 0.05).There was no significant difference in the expression of HO-2 mRNA and HO-2 between the 4 groups ( P > 0.05).Conclusion HO-1 in renal tissues has protective effects on renal function during septic shock in rats.