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

目的 探讨己酮可可碱(PTX)预处理对大鼠肾缺血-再灌注损伤(IRJ)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.再灌注组(IRI组)、FTX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45 min后关闭腹腔.通过无损伤动脉夹阻断双肾血流45 min建立大鼠的肾IRI模型.FTX组术前0.5 h予FTX 20rng/kg静脉注射,术中PTX 6 mg/(kg·h)微泵维持.SO组、IRI组术前0.5 h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1 h、4 h、24 h 5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)、细胞问黏附分子-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,FTX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、1 h、4 h、24 h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4 h,24 h显著下降(P<0.01),肾组织匀浆的SOD水平在再灌注后4 h、24 h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 FTX对肾IRI有保护作用,该作用可能与FTX直接抑制肾组织中TNF-α的表达有关,从而减轻了氧化应激、抑制了ICAM-1的表达,减轻炎性细胞肾内浸润而发挥保护作用.

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

Objective To investigate the protective effect of penotoxffylline (PTX) on renal iscbemia-reperfusion injury (IRI) and its mechanisns. 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 FIX treated group. The rat model of renal IRI was established with occlusion of left and fight kidney pedicle for 45 minutes. Sham rats underwent laparotomy without IR.Treated mrs received FIX 20 mg/kg at 30 minutes before operation through their tail vein,tben PTX 6 mg/(kg·h) IV with pump. SO group and IRI group rots 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 reperfitsion. Results After IRI, renal tubular epithelial cells manifested swelling, degeneration, necrosis, and inflammatory ceils infiltration. After treated with PTX, the pathological change of the kidney was significantly alleviated, and inflammatory cells infiltration reduced. In FIX 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 bemegenate of kidney in FIX group were significandy lower at 0 h, 1 h,4 h and 24 h after reperfiJsion (P<0.05). Compared with IRI group, the levels of MDA, ICAM-I in homogenate of kidney in FIX group were obviously lower at4 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 ceils infiltration in kidney.