氢吗啡酮对肾缺血再灌注损伤大鼠细胞凋亡的影响及其机制

Effect of hydromorphone on apoptosis of renal ischemia reperfusion injury in rats and its underlying mechanisms

目的探讨氢吗啡酮对大鼠肾缺血再灌注损伤(IRI)细胞凋亡的影响及其机制。方法将SD大鼠分为假手术组、实验组和模型组,每组15只。用夹闭双侧肾蒂构建肾缺血再灌注损伤模型。实验组于缺血即刻经股静脉注射氢吗啡酮4mg·kg-1,假手术组和模型组给予等容量乳酸钠林格氏液。用TUNEL法检测肾组织细胞凋亡,蛋白免疫印迹法检测肾组织B淋巴瘤-xl基因(Bcl-xl)、Bcl-2相关X蛋白(Bax)表达。结果假手术组、模型组、实验组细胞凋亡率分别为(5.26±2.31)%,(69.52±10.42)%,(23.15±2.63)%;Bax蛋白相对表达量分别为0.06±0.02,1.69±0.05和1.02±0.32;Bcl-xl蛋白分别为0.89±0.21,0.22±0.03和0.88±0.15,假手术组和实验组分别与模型组比较,差异均有统计学意义(均P<0.05)。结论氢吗啡酮可减轻大鼠IRI程度,保护大鼠肾功能,其机制与调控肾组织凋亡相关因子的表达抑制细胞凋亡相关。

Objective To investigate the effect and mechanism of hydromorphone on apoptosis of renal ischemia-reperfusion injury(IRI) cells in rats. Methods SD rats were randomly divided into sham-ope-ration group, test group and model group according to their body weight, with 15 rats in each group. Renal ischemia-reperfusion injury model was established by clipping bilateral renal pedicles. The test group was injected with hydromorphone 4 mg·kg-1 via femoral vein immediately after ischemia, while the sham-operation group and the model group were given equal amount of Ringer’s solution of sodium lactate. The apoptosis of kidney tissue was detected by TUNEL method. The expression of B lymphoma-xl gene(Bcl-xl) and Bcl-2 related X protein(Bax) in kidney tissue was detected by qPCR and Western blot. Results The apoptosis rates of the sham-operation group, model group and test group were(5.26±2.31)%,(69.52±10.42)%,(23.15±2.63)%;the relative expression of Bax were 0.06±0.02, 1.69±0.05 and 1.02±0.32;the relative expression of Bcl-xl were 0.89±0.21, 0.22±0.03 and 0.88±0.15, there were significant differences between the sham-operation group and the test group compared with the model group(all P<0.05). Conclusion Hydromorphone can alleviate IRI and protect renal function in rats. Its mechanism is related to the regulation of the expression of apoptosis-related factors in renal tissue and inhibiting apoptosis.