盐酸曲美他嗪预处理对大鼠肾脏急性缺血再灌注损伤的影响

摘要

目的：观察盐酸曲美他嗪（ TMZ）预处理对大鼠肾组织急性缺血再灌注损伤（ IRI）的影响。方法选择SD大鼠90只，随机均分为A、B两组：A组给予TMZ 10 mg／kg灌胃5 d后，建立缺血再灌注（IR1）、缺血再灌注后处理（IPO1）、假手术（S1）模型；B组生理盐水灌胃5 d后，建立缺血再灌注（IR2）、缺血再灌注后处理（IPO2）、假手术（S2）模型。检测各组末次恢复肾脏血供0、6、12、24、48 h后血清SCr、BUN、NGAL、IL-18水平；HE染色光镜下观察缺血-再灌注石蜡包埋切片肾组织损伤形态学改变。结果 IR1组与IPO1组相比，在各时间点各指标均无显著性差异。 IR1组与IR2组相比，在6 h时IR2组的NGAL、IL-18、肾小管损伤程度评分上升，12 h时BUN亦上升，24 h时IR2组的各项指标均高于IR1组，48 h时BUN、SCr高于IR1组（P均＜0．05）。 IPO1组与IPO2组相比，在6 h时IPO两组的NGAL明显上升，12 h时除SCr外均上升，24 h时除NGAL外其他指标均高于IPO1组，48 h时BUN、SCr、肾小管损伤评分程度高于IPO1组（ P均＞0．05）。 IR1组与IPO2组相比，在6 h时IPO2组NGAL上升，12 h时除SCr外其他指标均高于IR1组，48 h时SCr仍显著高于IR1组（P均＞0．05）。结论在大鼠肾脏IRI发生之前即预防性使用TMZ可减轻其肾功能损伤。%Objective To observe the effect of trimetazidine hydrochloride (TMZ) preconditioning on rats with acute re-nal ischemia-reperfusion injury (IRI).Methods Ninety rats were randomly divided into two groups:group A and group B. Rats in the group A were fed with TMZ 10 mg/kg for 5days and we established the animal models of acute renal ischemia-reperfu-sion injury (IR1), ischemia reperfusion postprocessing (IPO1) and sham operation (S1).Rats in the group B were fed with normal saline for 5 days by gavage and we established the animal models of acute renal ischemia-reperfusion injury (IR2), ische-mia reperfusion postprocessing (IPO2) and sham operation (S2).Serum Scr, BUN, NGAL and IL-18 levels were determined at the end of 0, 6, 12, 24 and 48 h after restoring the renal blood flow.Morphology changes of renal tissues were observed under HE staining microscopy.Results There was no significant difference in all above levels at different time points between groups IR1 and IPO1.NGAL, IL18 and renal tube injury score at 6 h increased in the IR2 group as compared with those of the IR1 group, and BUN was also increased significantly at 12 h.All the levels of IR2 group were higher than those of the IR1 group at 24 h.The levels of BUN and Src in the IR1 group were higher than the IR1 group at 48 h (all P<0.05).When we compared the IPO1 and IPO2 groups, the levels of NGAL in the two groups increased in 6 h, all levels were increased at 12 h except for Scr;at 24 h, all levels except for NGAL were higher in the IPO2 group than those of the IPO1 group.At 48 h, BUN, Scr and re-nal tube injury score were higher than those of the IPO1 group.When we compared IR1 group with IPO2 group, at 6 h, the NGAL level was increased, and all levels of the IPO2 group were increased except for Scr at 12 h as compared with those of the IR1 group;at 48 h, the Scr level was higher than that of IR1 group (all P<0.05).Conclusions The preventive use of TMZ might alleviate the damage of renal function before renal IRI.