标题：PPARγ激动剂罗格列酮对大鼠肾脏再灌注损伤的保护作用

      作者：罗京    (巴中市中心医院儿科，四川 巴中 610000)

      卷次： 2017年28卷12期

      【摘要】 目的 探讨罗格列酮(Rosiglitazone, RGZ)对大鼠肾脏缺血再灌注损伤的保护作用及作用机制。方法 将 30只大鼠按照双盲法随机均分成假手术组(Sham)、缺血性肾损伤组(IRI)和罗格列酮(RGZ)组，各 10只。利用血管夹夹闭左侧肾蒂，去除右肾诱导大鼠肾缺血再灌注损伤模型，缺血45 min，再灌注4 h。ELISA检测血清血清肌酐(Cr)、尿素氮(BUN)、肿瘤坏死因子(TNF-α)、白介素-8 (IL-8)和白介素-6 (IL-6)表达水平；RT-PCR检测TNF-α、IL-8和 IL-6 mRNA水平；硫代巴比妥酸(TBA)法检测丙二醛(MDA)的含量；Western blot检测 PPAR-γ和p-PPAR-γ表达水平；黄嘌呤氧化酶法检测过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)活性；过碘酸雪夫氏(PAS)染色检测肾组织病理形态。结果 IRI组血清Cr和BUN分别为(160.15±25.17) μmol/L和(90.22±16.17) mmol/L，较RGZ组的(47.16±5.13) μmol/L和(23.11±3.28) mmol/L明显增高，差异均有统计学意义(P<0.05)；IRI组肾脏病理损伤评分为(3±0.5)分，较RGZ组的(1±0.5)分明显增高，差异具有统计学意义(P<0.05)；IRI组血清中TNF-α、IL-8和 IL-6表达水平分别为(1 400±350) pg/mL、(1 200±300) pg/mL、(1 150±250) pg/mL，较RGZ组的(650±150) pg/mL、(450±120) pg/mL和(550±170) pg/mL明显增高，差异均具有统计学意义(P<0.05)；IRI组肾脏中TNF-α、IL-8和 IL-6 mRNA表达水平分别为(14.00±55)、(11.00±4.3)、(9.50±2.8)，较RGZ组的(5.50±1.7)、(6.40±2.1)和(3.80±1.3)明显增高，差异均具有统计学意义(P<0.05)；IRI组肾脏中MDA含量为(18.12±4.15) nmol/mg，较RGZ组[(7.12±1.15) nmol/mg明显增高，差异有统计学意义(P<0.05)；IRI组肾脏中CAT、GPX和 SOD活性分别为(8.77±1.52) U/mg、(7.22±1.03) U/mg和(6.54±1.22) U/mg，较RGZ组的(25.17±3.22) U/mg、(23.42±3.07) U/mg和(21.22±2.79) U/mg明显增高，差异均具有统计学意义(P<0.05)；IRI组肾脏中 p-PPAR-γ含量为(0.32±0.07)，较RGZ组的(0.51±0.11)明显降低，差异具有统计学意义(P<0.05)；IRI组与RGZ组 P PAR-γ表达差异无统计学意义(P>0.05)。结论 PPAR-γ激动剂罗格列酮对大鼠肾缺血再灌注损伤具有保护作用，能够减少肾脏病理改变，其作用机制与抑制氧化应激和炎症反应相关。
      【关键词】 罗格列酮；肾缺血再灌注损伤；炎症；氧化应激
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2017）12—1901—04

Protective effect of PPAR-γ agonist rosiglitazone on renal ischemia-reperfusion injury.
LUO Jing. Department ofPediatrics, the Central Hospital of Bazhong City, Bazhong 610000, Sichuan, CHINA
【Abstract】 Objective To explore the protective effect and potential mechanism of rosiglitazone (RGZ) on re-nal ischemia reperfusion injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly equally divided into 3groups: Sham group, ischemia-reperfusion injury (IRI) group, and RGZ group. The left renal pedicle was clamped withvascular clamp, and the model of renal ischemia-reperfusion injury was induced by removing right kidney with 45 min-utes of ischemia and 4 hours of reperfusion. The expression of creatinine (Cr), blood urea nitrogen (BUN), tumor necro-sis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the serum were determined by en-zyme-linked immunosorbent assay (ELISA). The mRNA level IL-8, TNF-α, and IL-6 in the kidney were evaluated byRT-PCR. The content of malondialdehyde (MDA) was by measured by thiobarbituric acid (TBA) method. The expres-sion of peroxisome proliferator-activated receptor γ (PPAR-γ) and p-PPAR-γ were evaluated by Western blot. The activ-ities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured by xanthine oxi-dase. The kidney morphology was evaluated by periodic acid-Schiff (PAS). Results The serum expression level of Crand BUN in the IRI group were respectively (160.15±25.17) μmol/L and (90.22±16.17) mmol/L, which were significantlyhigher than (47.16±5.13) μmol/L and (23.11±3.28) mmol/L in the RGZ group (P<0.05). The renal pathological damagescore in the IRI group was (3±0.5) points, which was significantly higher (1±0.5) points in the RGZ group (P<0.05). Theserum expression level of TNF-α, IL-8 and IL-6 in the IRI group were (1 400±350) pg/mL, (1 200±300) pg/mL, (1 150±250) pg/mL, respectively, which were all significantly higher than corresponding (650±150) pg/mL, (450±120) pg/mL,(550±170) pg/mL in the RGZ group (P<0.05). The mRNA expression levels of TNF-α, IL-8, and IL-6 in the IRI group·论 著·doi:10.3969/j.issn.1003-6350.2017.12.003基金项目：四川省医院科技基金（编号：2016PY0)