缺血再灌注对一氧化氮和细胞凋亡的影响及促肝细胞生长素的干预研究

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目的观察促肝细胞生长素(pHGF)对肾缺血再灌注损伤大鼠肾功能及肾小管上皮细胞凋亡的影响。方法雄性Sprague-Dawley大鼠32只,随机分为假手术对照组(Ⅰ组)、缺血再灌注组(Ⅱ组)、缺血再灌注前pHGF干预组(Ⅲ组)和缺血再灌注后pHGF干预组(Ⅳ组)。用无损伤动脉夹钳夹大鼠双侧肾蒂45min制成肾缺血再灌注损伤(RIRI)模型。假手术组只暴露双肾,不钳夹肾蒂。Ⅲ组和Ⅳ组分别在术前和术后腹腔注射pHGF50mg/kg。检测术后12h血清肌酐(Scr)和NO的浓度及肾小管上皮凋亡阳性细胞表达。结果Ⅱ组血清NO和Scr水平[(137.846±22.317)μmol/L、(120.85±22.237)μmol/L]明显高于Ⅰ组[(73.98±8.356)μmol/L、(22.775±6.508)μmol/L;P<0.01],各项在Ⅲ组[(101.304±16.518)μmol/L、(60.413±10.197)μmol/L和Ⅳ组(104.778±26.911)μmol/L、(69.400±11.443)μmol/L]的表达水平明显较Ⅱ组下降(P<0.01)。Ⅱ组肾小管损伤程度评分和肾脏凋亡阳性细胞的表达[(1.950±0.093)分、(26.850±1.476)个]均较Ⅰ组[(0.125±0.117)分、(0.900±0.385)个]明显升高(P<0.01),两项指标在Ⅲ组[(0.913±0.125)分、(8.300±1.146)个]和Ⅳ组[(0.888±0.136)分、(9.000±0.869)分]均较Ⅱ组显著下调(P<0.01)。Ⅲ组和Ⅳ组间各项值比较差异均无统计学意义(P>0.05)。结论pHGF能显著降低血清NO和Scr水平,能显著抑制肾小管上皮细胞凋亡,对IARF在肾脏结构及功能上既有保护作用又有治疗作用。 Objective To investigate the effects of hepatocyte growth promoting hormone (PHGF) on renal function and renal tubular epithelial cell apoptosis in rats with renal ischemia-reperfusion injury. Methods Thirty - two male Sprague - Dawley rats were randomly divided into 4 groups: sham operation group (group Ⅰ), ischemia - reperfusion group (Ⅱ group), pHGF group (Ⅲ group) and ischemia - reperfusion group pHGF intervention group (Ⅳ group). Renal ischemia-reperfusion injury (RIRI) model was established by clamping the bilateral renal pedicles for 45 minutes with an artery-lesion-free artery. Sham-operated group only exposed both kidneys, not clamp the renal pedicle. Group Ⅲ and group Ⅳ were injected intraperitoneally with pHGF 50 mg / kg before and after operation respectively. The concentrations of serum creatinine (Scr) and nitric oxide (NO) and the expression of apoptotic positive cells in renal tubular epithelial cells were detected 12 h after operation. Results The levels of serum NO and Scr in group Ⅱ were significantly higher than those in group Ⅰ [(137.846 ± 22.317) μmol / L, (120.85 ± 22.237) μmol / L] ; P <0.01], and all the differences were statistically significant between group Ⅲ [(101.304 ± 16.518) μmol / L, (60.413 ± 10.197) μmol / L and group Ⅳ (104.778 ± 26.911) μmol / L and (69.400 ± 11.443) μmol / The expression level was significantly lower than the group Ⅱ (P <0.01). The score of renal tubular injury and the expression of renal apoptotic cells in group Ⅱ [(1.950 ± 0.093) and (26.850 ± 1.476)] were significantly higher than those in group Ⅰ [(0.125 ± 0.117) and (0.900 ± 0.385)], respectively (P <0.01). The two indexes were significantly higher in group Ⅲ than those in group Ⅲ [(0.913 ± 0.125) vs (8.300 ± 1.146) and group Ⅳ [(0.888 ± 0.136) and (9.000 ± 0.869) Group was significantly down-regulated (P <0.01). There was no significant difference between the three groups and the four groups (P> 0.05). Conclusion pHGF can significantly reduce the levels of NO and Scr in serum, significantly inhibit the apoptosis of renal tubular epithelial cells, and have both protective and therapeutic effects on the structure and function of IARF.
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