机构地区:[1]山西医科大学第二医院肾内科,太原030001 [2]山西省人民医院肾内科
出 处:《中国药物与临床》2014年第6期712-714,I0001,共4页Chinese Remedies & Clinics
基 金:国家自然科学基金(30971380)
摘 要:目的探讨中介素(IMD)后处理对大鼠肾脏缺血再灌注损伤(IRI)中肿瘤坏死因子(TNF)-ɑ与白细胞介素(IL)-6表达的影响。方法将24只健康雄性SD(Sprasue-Dawley)大鼠随机分为正常对照组、IRI组、0.9%氯化钠注射液组、IMD后处理组。动物切除右肾后,饲养1周后制作肾脏IRI模型(夹闭左肾动脉45 min),24 h后留取肾组织与血清,0.9%氯化钠注射液组于再灌注前5 min 0.9%氯化钠注射液1 ml腹腔注射,IMD后处理组于再灌注前5 min IMD(2 nmol/kg)溶于1ml生理盐水后腹腔注射。过碘酸雪夫(PAS)染色观察肾组织的病理变化,半定量分析肾脏病理损伤;全自动生化仪常规检测血清尿素氮和肌酐;酶联免疫吸附试验(ELISIA)法检测血清IL-6和TNF-ɑ的表达。结果 PAS染色结果显示,IRI组肾小管和间质病理损伤显著重于正常对照组,病理评分为(0.32±0.12),(6.87±0.72)(P<0.05),IMD后处理组病理损伤(病理评分为4.33±0.81)则显著轻于IRI组,表现为细胞坏死,刷状缘脱落及管型减少(P<0.05)。与正常对照组相比,IRI组尿素氮和肌酐均显著增高(P<0.05);与IRI组相比,IMD后处理组尿素氮和肌酐显著下降(P<0.05)。与正常对照组相比,IRI组IL-6与TNF-ɑ的表达显著增高(P<0.05);而与IRI组相比,IMD后处理组IL-6与TNF-ɑ的表达则显著降低(P<0.05)。IRI组与0.9%氯化钠注射液组以上指标相比差异均无统计学意义(P>0.05)。结论 IMD后处理可减轻肾脏缺血再灌注损伤,其机制至少与抑制炎症因子IL-6与TNF-ɑ生成有关。Objective To investigate the effects of intermedin (IMD) postconditioning on interleukin-6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) expression on renal ischemia-reperfusion injury (IRI) in rats. Methods A total of 24 male Sprasue-Dawley (SD) rats were randomly allocated to normal control, IRI, saline and IMD postconditioning group, respectively. Following right renal resection, the IRI model was constructed by clamping the left renal artery for 45 min at week 1. This was followed by sampling of the renal tissues and sera at 24 h. The 1 ml normal saline was peritoneally injected in all groups, and with the addition of IMD (2 nmol/kg) solved in 1 ml normal saline in the IMD postconditioning group, at 5 min prior to reperfusion. The specimens were subjected to PAS staining for semi-quantitative analysis on the pathologic changes of the kidney. An automated instrument was employed to assay the levels of blood urea nitrogen (BUN) and serum creatinine (SCr). The expression of IL-6 and TNF-α was measured by ELISIA. Results Compared with normal control group, the IRI group yielded significantly aggravated tubulointerstitial pathological injury and markedly increased pathologic scores (0.32±0.12) vs. (6.87±0.72) (both P〈0.05). The IMD postcon-ditioning group had a significantly attenuated pathologic injury (4.33 ±0.81), as evidenced by minor cell death, loss of brush border and casts (all P〈0.05). Compared with normal control group, the significantly increased levels of BUN and Scr as noted in IRI group (both P〈0.05) could be markedly reduced by IMD postconditioning (both P〈0.05). A-gain, compared with normal control group, the impressively increased levels of IL-6 and TNF-ɑ as found in IRI group (both P〈0.05) could be substantially suppressed by IMD postconditioning (both P〈0.05). The difference in the afore-mentioned indices between normal control group and IRI group was unremarkable (all P〈0.05). Conclusion IMD postconditioni
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