IPC、IPO和IPC-IPO对胰腺冷缺血再灌注损伤保护作用的对比研究

Comparative Study of Protective Effects of IPC,IPO,and IPC-IPO on Ischemic Reperfusion Injury of Pancreas Allograft of Rats

目的对比研究缺血预处理(IPC)、缺血后处理(IPO)以及二者联合应用(IPC-IPO)对胰腺缺血再灌注损伤(IRI)的保护作用。方法建立SD大鼠糖尿病模型,24只糖尿病大鼠用于建立胰腺移植模型,随机分为4组,每组6只:I/R组、IPC组、IPO组和IPC-IPO组,另6只糖尿病SD大鼠为假手术组(SO组),检测各组大鼠再灌注前、后血糖水平以及再灌注后2 h移植胰腺组织中SOD和MDA含量,并采用TUNEL法观察移植胰腺组织细胞凋亡情况。结果各组大鼠再灌注前血糖水平之间的差异均无统计学意义(P>0.05);SO组大鼠再灌注后血糖水平明显高于其他4组(P<0.01);I/R组、IPC组、IPO组和IPC-IPO组大鼠再灌注后血糖水平均比再灌注前明显下降(P<0.05或P<0.01),I/R组又明显高于后3组(P<0.01),而后3组大鼠再灌注后血糖水平间的差异均无统计学意义(P>0.05)。再灌注后IPC组、IPO组和IPC-IPO组大鼠与I/R组比较MDA含量均明显降低(P<0.01),而SOD含量均明显升高(P<0.01);与SO组比较,I/R组、IPC组、IPO组和IPC-IPO组大鼠MDA均明显升高(P<0.01),而SOD含量均明显降低(P<0.01);IPC组、IPO组和IPC-IPO组大鼠MDA及SOD含量的差异无统计学意义(P>0.05)。I/R组、IPC组、IPO组和IPC-IPO组大鼠再灌注后2 h胰腺组织中AI值分别为(47.31±4.52)%、(26.25±3.17)%、(24.73±3.62)%和(25.5±4.15)%,均明显高于SO组的(3.16±0.53)%,P<0.01;IPC组、IPO组和IPC-IPO组大鼠与I/R组比较AI值明显降低(P<0.01);而IPC组、IPO组和IPC-IPO组间AI值的差异均无统计学意义(P>0.05)。病理组织学检查显示,I/R组大鼠胰腺损伤最为明显。结论 IPO和IPC对胰腺的IRI均有相似的保护作用。IPC与IPO联合应用对大鼠胰腺IRI和细胞凋亡的保护作用无叠加效应。

Objectives To explore the mechanisms by which ischmic preconditioning（IPC）,ischemic postconditioning（IPO） and IPC-IPO exert influence on ischemic reperfusion injury（IRI） of the graft of SD rat after pancreas transplantation.Methods After the establishment of diabetic SD rats model by using streptozotocin,24 rats suffered from pancreas transplantation and were randomly averagely divided into four groups： I/R group,IPC group,IPO group,and IPC-IPO group.Six diabetic SD rats suffered with sham operation were served as SO group.The blood glucose level of rats in each group was detected before and after reperfusion,the contents of malonaldehyde（MDA） and super oxide dismutase（SOD） of pancreas allograft were tested at 2 h after reperfusion, and the apoptosis index（AI） of pancreas allograft was monitored by using TUNEL method.Results The blood glucose level of rats in each group was not significantly different（P0.05）.In SO group,the blood glucose level of rats was significantly higher than other groups（P0.01）.The blood glucose levels of rats after reperfusion decreased from the levels before reperfusion in I/R group,IPC group,IPO group,and IPC-IPO group（P0.05 or P0.01）,furthermore the blood glucose level of rats in I/R group was significantly higher than that in above-mentioned three groups（P0.01）,although among which the difference was not markedly（P0.05）.When compared with I/R group,the MDA contents of rats after reperfusion in IPC group,IPO group,and IPC-IPO group decreased（P0.01）,while the SOD contents of rats after reperfusion increased（P0.01）. In rats of SO group,the MDA and SOD contents were significantly higher and lower than other groups,respectively（P0.01）.The MDA and SOD contents in IPC group,IPO group,and IPC-IPO group were not different（P0.05）.The AI of pancreas allograft at 2 h after reperfusion in I/R group（（47.31±4.52）%）,IPC group（（26.25±3.17）%）,IPO group（（24.73±3.62）%）,and IPC-IPO group（（25.5±4.15）%） were higher than that in SO group（（3.16±0.53）%）,P0.01.The AI of pancreas allograft in IPC group,IPO group,and IPC-IPO group were not different（P0.05）,but they were lower than that in I/R group（P0.01）.Pathological results showed that injury of pancreas allograft in I/R group was most severe.Conclusions IPO and IPC are associated with comparable effectiveness to protect graft from IRI during pancreas transplantation.The combined protective effects of IPC and IPO do not appear to be additive,which is equal to IPC or IPO alone.