己酮可可碱对大鼠肾缺血-再灌注损伤的保护作用及其机制  

Protective effect and mechanisms of penotoxifylline on ischemia-reperfusion injury in rat kidneys

作　　者：杨向红[1] 陈江华[1] 

机构地区：[1]浙江大学医学院附属第一医院肾脏病中心,杭州310006

出　　处：《中华急诊医学杂志》2008年第11期1171-1175,共5页Chinese Journal of Emergency Medicine

摘　　要：目的探讨己酮可可碱（PTX）预处理对大鼠肾缺血．再灌注损伤（IRI）的保护作用及其具体保护机制。方法75只雄性SD大鼠随机分为3组：假手术组（SO组）、缺血一再灌注组（IRI组）、PTX治疗组（PTX组），每组25只。SO组：单纯剖腹术，游离双侧肾蒂血管后不作结扎，等待45min后关闭腹腔。通过无损伤动脉夹阻断双肾血流45min建立大鼠的肾IRI模型。PTX组术前0．5h予PTX20mg／kg静脉注射，术中PTX6mg／（kg·h）微泵维持。SO组、IRI组术前0．5h予等量生理盐水静脉注射及微泵维持。3组分别于缺血前、缺血．再灌注即刻、再灌注后1h,4h、24h5个时间点监测肾功能、肾脏病理及肾组织匀浆的丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）变化情况。采用单因素方差分析，组间两两比较采用q检验，并对部分数据行相关性分析。结果肾IRI后，表现为肾小管上皮细胞不同程度的肿胀、变性、坏死，炎性细胞浸润，给予PTX预处理后肾脏病理改变明显减轻，炎性细胞浸润减少。与SO组相比，IRI组在再灌注后各时间点血清肌酐水平，肾小管损伤评分，肾组织匀浆的TNF-α水平、ICAM-1水平显著升高（P〈0．01），肾组织匀浆的SOD水平显著下降（P〈0．01）；与IRI组相比，PTX组在相应时间点的血清肌酐水平、肾小管损伤评分显著下降（P〈0．05）；在再灌注即刻、1h、4h、24h肾组织匀浆的TNF—α水平明显下降（P〈0．05），肾组织匀浆的MDA、ICAM-1水平在再灌注后4h，24h显著下降（P〈0．01），肾组织匀浆的SOD水平在再灌注后4h、24h显著升高（P〈0．05）。相关性分析显示，TNF-α与MDA、SOD、ICAM-1之间的相关系数分别为0．801、-0．895、0．838，（P〈0．01）结论PTX对肾IRI有保护作用，该作用可能与PTX直接抑制肾组织中TNF-α的表达有关，从而�Objective To investigate the protective effect of penotoxifyiline （PTX） on renal ischemia-reperfusion injury （IRI） and its mechanisms. Method Seventy-five male SD rats were randomly divided into three groups with 25 rats in each group： the sham operated controls, IRI group and PTX treated group. The rat model of renal IRI was estabhshed with occlusion of left and right kidney pedicle for 45 minutes. Sham rats underwent laparotomy without IR. Treated rats received PTX 20 mg/kg at 30 minutes before operation through their tail vein, then PTX 6 mg/（kg.h） IV with pump. SO group and IRI group rats were IV normal saline equivalently. The pathological change of kidney, serum creatinine （sCr） values and the levels of MDA, SOD, TNF-α and ICAM-1 in homogenate of kidney tissue were measured before ischemia, 0, 1, 4, and 24 hours after reperfusion. Results After IRI, renal tubular epithelial cells manifested swelling, degeneration, necrosis, and inflammatory cells infiltration. After treated with PTX, the pathological change of the kidney was significantly alleviated, and inflammato- ry ceils infiltration reduced. In PTX group, the kidney tissue pathological change was ameliorated, and the values of serum Cr, the scores of renal tubules were significantly lower than those in IRI group （ P 〈 0.05）. Compared with IRI group, the levels of TNF-α in homogenate of kidney in PTX group were significantly lower at 0 h, 1 h,4 h and 24 h after reperfusion （ P 〈 0.05）. Compared with IRI group, the levels of MDA, ICAM-l in homogenate of kidney in FIX group were obviously lower at 4 h, 24 h after reperfusion （ P 〈 0.05）, while the level of SOD in homogenate of kidney was significantly higher （ P 〈 0.05）. TNF-α correlated with levels of MDA, SOD, ICAM- 1 （ r =0.801, -0.895,0.838,and P 〈0.01）. Conclusions PTX had the protective effect on renal IRI by directly inhibited expression of TNF-α in kidney tissue, then decreased expression of MDA, ICAM-1 and ameliorated the inflammatory cells infi

关 键 词：己酮可可碱 缺血-再灌注 肾脏 功能 痛理 丙二醛 超氧化物歧化酶 肿瘤坏死因子 细胞问黏附分子 

分 类 号：R285.5[医药卫生—中药学]