糖尿病肾病患者尿液类胰蛋白酶水平检测及其病理意义分析

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目的肥大细胞与糖尿病肾病(diabetic nephropathy,DN)的一些临床病理指标具有显著相关性,但确切病理意义仍有需进一步论证。文中通过检测肥大细胞特异性表达的含量最为丰富的丝氨酸蛋白酶——类胰蛋白酶在DN患者尿液中的表达情况,分析其与DN发生发展的关系,探讨类胰蛋白酶和肥大细胞与DN肾组织损伤的关系。方法收集2012年1月至2013年6月来南京军区南京总医院全军肾脏病研究所就诊的103例DN患者尿液,分为DN早期组(微量蛋白尿期,10例)、DN中期组(显性蛋白尿期,31例)和DN晚期组(肾功能不全期,62例),同时收集20例正常人尿液作为对照组;利用ELISA方法检测尿中类胰蛋白酶水平;比较分析对照组、DN早期组、DN中期组和DN晚期组尿液中类胰蛋白酶的变化情况,并分析尿液中类胰蛋白酶水平与患者各临床指标的相关性。结果 1对照组中17人尿液中未检测到类胰蛋白酶(<1.0ng/mg肌酐),而DN组尿液中类胰蛋白酶的水平显著升高,并表现为随DN的发展而逐渐增加的趋势早期组(11.6±10.5)ng/mg肌酐、中期组(29.7±19.2)ng/mg肌酐、晚期组(44.6±43.4)ng/mg肌酐。2相关性分析显示,DN患者尿液类胰蛋白酶水平与血肌酐(r=0.325,P<0.01)、血胱蛋白酶抑制剂C(r=0.391,P<0.01)、血尿素氮(r=0.27,P<0.01)、24 h尿蛋白(r=0.389,P<0.01)、尿C3(r=0.276,P<0.05)、尿视黄醇结合蛋白(r=0.365,P<0.01)、尿溶菌酶(r=0.461,P<0.01),尿N-乙酰-β-葡萄糖苷酶(r=0.568,P<0.01)、尿肾损伤分子-1(r=0.434,P<0.05)和尿IL-18水平(r=0.375,P<0.05)均具有相关性,而与年龄、性别、空腹血糖、餐后血糖、糖化血红蛋白水平、血三酰甘油浓度、高密度脂蛋白和低浓度脂蛋白浓度则无明显相关性。结论肥大细胞在DN中具有重要作用,肥大细胞很可能是DN防治的有效新靶标。 The purpose of mast cells and diabetic nephropathy (DN) some of the clinical and pathological indicators have a significant correlation, but the exact pathological significance still needs further demonstration. In this paper, by detecting the expression of mast cell-specific serine protease-tryptase in DN patients with urine expression, analysis of its relationship with the occurrence and development of DN to explore the relationship between tryptase and mast cells and DN kidney tissue Injury relationship. Methods A total of 103 patients with DN who were admitted to Nanjing General Hospital of Nanjing Military Region from January 2012 to June 2013 were enrolled in this study. Urine was divided into DN early stage (microalbuminuria, 10 cases), DN midterm group (Dominant proteinuria, 31 cases) and DN group (62 cases with renal dysfunction). Meanwhile, 20 cases of normal urine were collected as control group. The levels of tryptase in urine were detected by ELISA. The changes of tryptase in the urine of early stage group, DN middle stage group and DN late stage group were analyzed. The correlation between urine tryptase level and each clinical index was analyzed. Results 1 Trypsin (<1.0 ng / mg creatinine) was not detected in the urine of 17 subjects in the control group, whereas the tryptase level was significantly increased in the urine of DN group and showed a gradual increase with the development of DN (11.6 ± 10.5) ng / mg creatinine, intermediate group (29.7 ± 19.2) ng / mg creatinine, and advanced group (44.6 ± 43.4) ng / mg creatinine. 2 The correlation analysis showed that the urinary trypsin levels in patients with DN were positively correlated with serum creatinine (r = 0.325, P <0.01), serum cystatin C (r = 0.391, P <0.01) (R = 0.369, P <0.01), urinary C3 (r = 0.276, P <0.05), urinary retinol binding protein (R = 0.468, P <0.01), urinary renal injury molecule-1 (r = 0.434, 18 levels (r = 0.375, P <0.05), but not with age, sex, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, triglyceride, HDL and low concentration lipoprotein No significant correlation. Conclusion Mast cells play an important role in DN. Mast cells are likely to be effective new targets for the prevention and treatment of DN.
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