STF083010对大鼠肾脏缺血再灌注损伤的肾保护作用

Renal protective role of STF083010 in ischemia-reperfusion injury in rats

目的探讨STF083010对大鼠肾脏缺血再灌注损伤(ischemia-reperfusion injury,IRI)的肾保护作用。方法健康雄性SD大鼠30只,随机分为假手术组、IRI组与STF083010组,每组10只。假手术组大鼠开腹后仅分离双侧肾动脉,不夹闭肾动脉;IRI组和STF083010组大鼠采用无创动脉夹同时夹闭左、右肾动脉45 min后放开,建立IRI模型;STF083010组大鼠建立IRI模型前2h腹腔注射STF083010 15mg/kg。缺血再灌注24h后,应用全自动生化仪检测3组大鼠血清尿素氮和肌酐水平,3组大鼠均行肾组织病理学PAS染色,采用免疫组织化学法检测肾组织XBP1、GRP78蛋白阳性表达率,采用实时荧光定量PCR检测肾组织XBP1、GRP78 mRNA表达水平。结果IRI组血清肌酐[(322.10±18.93)μmol/L]、尿素氮[(41.16±3.09)mmol/L]水平、肾小管损伤评分(202.50±9.15)高于STF083010组[(149.70±14.80)μmol/L、(25.22±3.81)mmol/L、129.50±5.49]和假手术组[(49.58±2.82)μmol/L、(7.56±0.70)mmol/L、25.88±1.46](P<0.05),STF083010组高于假手术组(P<0.05);IRI组和STF083010组大鼠肾组织GRP78蛋白阳性表达率[(27.16±3.98)%、(58.72±7.12)%]、GRP78 mRNA表达水平(0.086±0.007、0.335±0.023)、XBP1蛋白阳性表达率[(56.32±5.21)%、(29.83±3.78)%]、XBP1mRNA表达水平(0.172±0.053、0.088±0.054)高于假手术组[(4.86±2.30)%、0.015±0.001、(5.68±1.37)%、0.039±0.004](P<0.05),STF083010组GRP78蛋白阳性表达率和GRP78mRNA表达水平高于IRI组,XBP1蛋白阳性表达率和XBP1mRNA表达水平低于IRI组(P<0.05)。结论 STF083010可通过抑制XBP1表达,增加GRP78表达保护大鼠肾功能。

Objective To investigate the renal protective role of STF083010 in ischemia-reperfusion injury(IRI)in rats.Methods Thirty male SD rats were randomly divided into sham operation group,IRI group and STF080310 group,with10 rats in each group.In sham operation group,the bilateral renal artery was separated without clipping renal artery after opening abdomen.IRI models were established by clipping both the left and right renal arteries with non-traumatic clips,and the clips were removed 45 min later in IRI group and STF083010 group.STF083010 group was intraperitoneally injected with 15 mg/kg of STF083010 in 2 hbefore model establishment.After 24 hreperfusion,the serum urea nitrogen(BUN)and serum creatinine(SCr)levels were detected by automatic biochemical analyzer test in three groups.After PAS staining, the positive rates of XBP1 and GRP78 proteins in renal kidney tissue were detected by immunohistochemical method,and the expressions of XBP1 mRNA and GRP78 mRNA were detected by real-time fluorescence quantitative PCR.Results The SCr level,BUN level and renal tubule damage score were significantly higher in IRI group((322.10±18.93)μmol/L,(41.16±3.09)mmol/L,202.50±9.15)than those in STF083010 group((149.70±14.80)μmol/L,(25.22±3.81)mmol/L,129.50±5.49)and sham operation group((49.58±2.82)μmol/L,(7.56±0.70)mmol/L,25.88±1.46)(P<0.05),and in STF083010 group than those in sham operation group(P<0.05).The positive rates of GRP78 protein((27.16±3.98)%,(58.72±7.12)%),GRP78 mRNA levels(0.086±0.007,0.335±0.023),the positive rates of XBP1 protein((56.32±5.21)%,(29.83±3.78)%),and XBP1 mRNA levels(0.172±0.053,0.088±0.054)in IRI group and STF083010 group were significantly higher than those in sham operation group((4.86±2.30)%,0.015±0.001,(5.68±1.37)%,0.039±0.004)(P<0.05).The positive rate of GRP78 protein and GRP78 mRNA level were significantly higher in STF083010 group than those in IRI group,and the positive rate of XBP1 protein and XBP1 mRNA level were significantly lower than those in IRI group(P<0.05).Conclusion STF083010 can protect renal function by inhibiting the expression of XBP1 and improving the expression of GRP78 in rats.