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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 effect of STF083010 on renal ischemia-reperfusion injury (IRI) in rats. Methods Thirty male SD rats were randomly divided into sham operation group, IRI group and STF083010 group, with 10 rats in each group. The rats in sham-operated group were divided into two groups: the left renal artery and the renal artery were not clamped; the IRI group and STF083010 group were treated with noninvasive arterial clamp and the left and right renal artery were clamped for 45 min, then the IRI model was established; Rats in STF083010 group were intraperitoneally injected with STF083010 15mg / kg 2 hours before establishing IRI model. Serum urea nitrogen and creatinine were measured by automatic biochemical analyzer 24h after ischemia-reperfusion. The pathological changes of kidney were observed by PAS staining. Immunohistochemistry was used to detect the positive expression of XBP1 and GRP78 The expression of XBP1 and GRP78 mRNA in renal tissues were detected by real-time fluorescence quantitative PCR. Results The levels of serum creatinine [(322.10 ± 18.93) μmol / L], urea nitrogen (41.16 ± 3.09 mmol / L) and tubule damage score (202.50 ± 9.15) in IRI group were significantly higher than those in STF083010 group [(149.70 ± 14.80) μmol (25.22 ± 3.81mmol / L, 129.50 ± 5.49) and sham operation group (49.58 ± 2.82μmol / L, 7.56 ± 0.70mmol / L, 25.88 ± 1.46, P <0.05) and STF083010 (27.16 ± 3.98)% and (58.72 ± 7.12)%, respectively. The GRP78 mRNA expression level in the IRI group and STF083010 group (0.086 ± 0.007) was significantly higher than that in the sham operation group (P <0.05) , 0.335 ± 0.023, respectively). The positive rate of XBP1 protein expression was (56.32 ± 5.21)% and (29.83 ± 3.78)% respectively. The expression level of XBP1 mRNA in the sham operation group was significantly higher than that in the sham operation group (4.86 ± 2.30 and 0.172 ± 0.053 and 0.088 ± 0.054, %, 0.015 ± 0.001, (5.68 ± 1.37)%, 0.039 ± 0.004] (P <0.05). The positive rate of GRP78 protein and the expression of GRP78 mRNA in STF083010 group were higher than those in IRI group, the expression of XBP1 protein and XBP1 mRNA were lower IRI group (P <0.05). Conclusion STF083010 can protect renal function of rats by inhibiting the expression of XBP1 and increasing GRP78 expression.