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抗体芯片在糖尿病肾病大鼠尿液细胞因子同步检测中的应用
作者:倪杰  戴厚永  郑敏  吕林莉  刘必成 
单位:东南大学附属中大医院 肾脏病研究所, 江苏 南京 210009
关键词:蛋白质阵列分析 糖尿病肾病 尿液 细胞因子 大鼠 
分类号:R-33; R587.2
出版年·卷·期(页码):2012·31·第三期(249-253)
摘要:

目的:应用抗体芯片技术同步检测糖尿病肾病(DN)大鼠尿液中多种细胞因子的水平,以初步探讨其在寻找DN生物标志物研究中的意义。方法:高糖高脂喂养联合低剂量链脲佐菌素(STZ)单次腹腔注射SHR大鼠诱导出2型DN模型,随机分为DN组(D组)和厄贝沙坦治疗组(T组,予厄贝沙坦50 mg·kg-1·d-1灌胃),并以同周龄WKY大鼠作对照(N组)。8周后应用RayBio®大鼠细胞因子抗体芯片,同步检测各组大鼠24 h尿液中19种细胞因子水平的变化。结果:与N组相比,D组大鼠尿液中性粒细胞趋化因子(CINC)-3和Fractalkine细胞因子的水平明显升高。厄贝沙坦治疗后尿液CINC-3、Fractalkine、干扰素(IFN)-γ、白介素(IL)-1α、IL-10、脂多糖诱导的CXC趋化因子(LIX)和肿瘤坏死因子(TNF)-α共7种细胞因子水平显著性下降。T组与N组细胞因子水平差异无统计学意义。结论:首次将抗体芯片技术应用于DN模型的研究中,证实尿液中某些细胞因子水平的变化与DN的发生发展和转归密切相关,为DN新型生物标志物的发现提供了新的途径。

Objective: To evaluate the influence of irbesartan on the urinary excretion of cytokines in rat with diabetic nephropathy by antibody microarray. Methods: 6-week old SHR were fed with high-lipids and high-sucrose diets and treated intraperitoneal injection with 35 mg·kg-1 streptozotocin(STZ) to induce diabetic nephropathy. Then the rats were randomly divided into diabetic nephropathy group D and irbesartan-treatment group T(administered with irbesartan 50 mg·kg-1·d-1). Wistar-Kyoto(WKY) rats were used as controls(N). At the end of 8 weeks, rat cytokine antibody array I(RayBio®) coated with 19 specific cytokine antibodies were probed with rat urine samples and the relative cytokine levels were compared among different groups. Results: Compared to the control rats, an increasing excretion of urinary neutrophil chemoattractant-3(CINC-3) and fractalkine was found in rats with diabetic nephropathy. After irbesartan administration, there was significant decrease in the levels of urinary cytokines including CINC-3,Fractalkine, IFN-γ, IL-1α, IL-10, lipopolysaccharide-induced CXC chemoattactant(LIX) and TNF-α. No statistically significant changes were found between T group and N group. Conclusion: Antibody microarray was firstly applied in profiling urinary cytokine in DN animal models. A close correlation between certain urinary cytokine levels with the development of DN has been revealed, indicating a promising role of identifying urinary cytokines in diabetic nephropathy.

参考文献:

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