观察促肝细胞生长素(hepatocyte growth-promoting factor，pHGF)对大鼠肾缺血再灌注损伤肾功能及肾脏抑凋亡调节蛋白Bcl-2和促凋亡调节蛋白Bax表达的影响。

将雄性Sprague-Dawley大鼠32只随机分为4组(n= 8)，假手术组、缺血再灌注组(I组)、缺血再灌注前pHGF干预组(Ⅱ组)和缺血再灌注后pHGF干预组(Ⅲ组)。用无损伤动脉夹钳夹大鼠双侧肾蒂45 min制成肾缺血再灌注损伤(renal ischemia reperfusion injury，RIRI)模型(Ⅱ组)。假手术组只暴露双肾，不钳夹肾蒂。Ⅱ组和Ⅲ组依照I组的方法制作RIRI模型后，再分别在术前和术后腹腔注射pHGF 50 mg/kg(0. 8 ml生理盐水稀释)。检测术后12 h血清肌肝(Scr)浓度、小管上皮细胞Bcl-2和Bax的表达。

假手术组Scr水平为(22. 775±6. 508)μmol/L, I组为(120. 850±22. 237)μmol/L，较假手术组显著升高(P<0. 01)。Ⅱ组和Ⅲ组Scr水平分别为(60. 413±10. 197)μmol/L和(69. 400± 11. 443)μmol/L，与I组比较，均有一定程度的降低，差异有显著意义(P<0.01)。假手术组小管上皮细胞抑凋亡调节蛋白Bcl-2表达为(2. 472±0.453)/L，I组为(19. 075±2. 330)/L，较假手术组上调，差异有显著意义(P<0. 01)，Ⅱ组和Ⅲ组Bcl-2分别为(58. 075±7. 765)/L和(56. 025±6. 481)/L，与I组比较，均显著上调，差异有显著意义(P<0. 01)。I组促凋亡蛋白Bax为(69.025±6. 550)/L较假手术组(2. 450±0. 639)/L，显著上升，差异有显著意义(P<0.01)，Ⅱ组和Ⅲ组Bax分别为(16. 175±2. 314)/L和(12. 875±1. 814)/L，较I组明显下调，差异有显著意义(P<0.01)。上述各项指标Ⅱ组和Ⅲ组间比较，差异无显著意义(P>0. 05)。

pHGF能显著上调抑凋亡调节蛋白Bcl-2和下调促凋亡调节蛋白Bax的表达，对并发重症特发性急性肾衰竭(IARF)在肾脏结构及功能上，既有保护作用，又有治疗作用。

To investigate the effects of hepatocyte growth-promoting factor (pHGF) onBcl-2 (anti-apoptotic protein), Bax (pro-apoptotic protein), and renal ischemia reperfusion injury (RIRI)in a rat model.

32 male Sprague-Dawley rats were divided into 4 groups (n= 8): Sham-operated control group, RIRI group (group I), one experimental group injecting pHGF 0. 8 ml (50 mg/kg, intra¬abdominal injection) before RIRI (group Ⅱ) ; and another experimental group injecting pHGF (50 mg/kg, intra-abdominal injection) after RIRI (group Ⅲ). The animals with RIRI exposed to 45 min bilateral renal pedicle clamping. All the rats in control group and group I were intra-abdomia injected equal volume of physiological saline (0. 8 ml) at the time when the rats in experimental groups were administered 0. 8 ml pHGF. 12 h after RIRI, samples for serum and the left renal tissue of each animal were taken. The serum sample was for analysis of expression of serum creatinine (Scr), and the renal tissue sample for evaluation of Bcl-2 and Bax and renal tubular epithelial cells injury degree score.

Compared with the expression of Scr in control group [(22. 775 ± 6. 508)μmol/L], that was markedly higher in group I[(120. 850±22. 237)μmol/L; P<0. 01]. While Scr production in groups Ⅱ [(60. 413±10. 197)μmol/L]and group Ⅲ[(69. 400±11. 443)μmol/L] were lower than those in group I (P<0. 01). The expression of Bcl-2 in tubular epithelial cells was moderately up regulated in group I [(19. 075 ± 2. 230)/L] in contrast to control group [(2. 475 ± 0. 453)/L], but significantly higher in group Ⅱ [(58. 075 ± 7. 765)/L]and group Ⅲ [(56. 025 ± 6. 481)/L] than in group I (P<0. 01). Bax level showed a marked increase in group I [(69. 025 ± 6. 550)/L] in contrast to control group [(2. 450±0. 639)/L,P<0. 01]. While it was significantly lower in group Ⅱ [(16. 175 ± 2. 314)/L] and group Ⅲ [(12. 875 ± 1. 814)/L] than in group I(P <0. 01). No statistical significance was detected between group Ⅱ and group Ⅲ concerning any detected parameters in the study (P>0. 05).

The laboratory investigation suggests that pHGF might be an effective pharmacological agent against renal IR injury according to the findings of the evaluated parameters, and protective effect by pHGF against renal IR injury might involved in the mechanisms up regulating Bcl-2 anti-apoptotic protein and down regulating Bax pro-apoptotic protein. It is likely that pHGF is a potential therapeutic agent in clinical RIRI circumstances.