罗格列酮对大鼠肾脏缺血再灌注损伤保护作用机制的研究

Mechanism of Protection by Rosiglitazone against Renal Ischemia-Reperfusion Injury in Rats

目的研究罗格列酮预处理对大鼠肾脏缺血再灌注损伤的保护作用,并初步探讨其保护机制。方法建立大鼠肾缺血再灌注损伤模型,将40只健康雄性SD大鼠按随机数字表法分为5组:假手术组(S组)、缺血再灌注组(IR组)、罗格列酮+缺血再灌注组(RIR组)、GW9662+缺血再灌注组(GIR组)、罗格列酮+GW9662+缺血再灌注组(RGIR组),每组8只。各实验组均于术后6、24、72h抽取下腔静脉血,并于术后24h采集肾脏组织。HE染色法光镜下观察肾组织形态、测定血清肌酐(Cr)含量、ELISA法测定血清丙二醛(MDA)和超氧化物歧化酶(SOD)含量、免疫组织化学法观察肾组织中细胞间黏附分子(ICAM-1)表达。结果 IR组肾小管评分及血清Cr、MDA含量较S组明显升高,血清SOD活性较S组降低,肾组织ICAM-1表达较S组增加(均P<0.05)。RIR组肾小管评分及血清Cr、MDA含量较IR组下降,血清SOD活性较IR组升高,肾组织ICAM-1表达较IR组下降(均P<0.05)。GIR组与IR组肾小管评分及血清Cr、MDA、SOD比较差异均无统计学意义(均P>0.05)。RGIR组与RIR组比较,肾小管评分及血清Cr、MDA含量显著上升,血清SOD活性下降,肾组织ICAM-1表达显著增高(均P<0.05)。结论罗格列酮预处理能通过激活过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor gamma,PPARγ)保护缺血再灌注损伤的肾脏,其作用机制可能包括抗氧化应激和抗炎作用。

Objective To study the protective effect of rosiglitazone pretreatment on renal is- chemia-reper{ution（I/R） injury in rats, and to preliminarily investigate its mechanism of action. Methods Renal I/R injury was induced in healthy male Sprague-Dawley rats. Forty rats were ran- domly divided into five groups：sham operation group（S group, n = 8）, I/R group（IR groupn= 8）, rosigli- tazoneq-I/R group （RIR groupn = 8）, GW9662 ＋ I/R group （GIR groupn = 8）, and rosiglitazone ＋ GW9662＋I/R group（RGIR groupn=8）. Venous blood samples were drawn from the inferior vena cava at 6,24 and 72 hours after operation,and kidney tissues were collected at 24 hours after oper- ation. Renal pathological changes were observed by atinine（Cr）,malonaldehyde（MDA） and superoxide HE staining. In addition,levels of serum cre dismutase（SOD） were determined. Intercellu-lar adhesion molecule-1 （ICAM-1） expression in kidney tissue was detected by immunohistochem istry. Results Compared with S group, I/R increased renal tubular scores, ICAM-1 expression and serum Cr and MDA contents, and decreased serum SOD activity（P（0.05）. Compared with IR group, rosiglitazone decreased renal tubular scores, ICAM-1 expression and serum Cr and MDA contents, and increased serum SOD activity（P（0.05）. Compared with RIR group, GW9662 increased renal tubular scores, ICAM-1 expression and serum Cr and MDA contents, and de creased serum SOD activity（P（0.05）. There were no significant differences in these parameters between GIR group and IR group（P〈0.05）. Conclusion Rosiglitazone pretreatment can protect the kidney against I/R injury through activating peroxisome proliferator-activated receptor gam- ma. The mechanisms may involve antioxidant and anti-inflammatory effects.