河北医科大学学报

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糖尿病肾病患者锌α2糖蛋白表达水平及其与临床病理关系的研究

  

  1. 河北医科大学第二医院肾内科,河北 石家庄 050000
  • 出版日期:2019-11-25 发布日期:2019-11-21
  • 作者简介:闫喆(1974-),女,河北石家庄人,河北医科大学第二医院副主任医师,医学博士,从事肾内科疾病诊治研究。
  • 基金资助:
    国家自然科学基金(81500539);河北省医学科学研究重点课题(ZL20140112)

Expression of  zinc-α2-glycoprotein in patients with diabetic nephropathy and its relationship with clinicopathological parameters#br#

  1. Department of Nephrology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Online:2019-11-25 Published:2019-11-21

摘要: [摘要]
〖HTH〗目的〖HTSS〗〖KG*2〗观察糖尿病肾病患者肾组织及尿液锌α2糖蛋白(zinc alpha 2 glycoprotein,ZAG)表达水平,并分析其与临床病理的关系。
〖HTH〗方法〖HTSS〗〖KG*2〗选择经肾活检确诊的糖尿病肾病患者89例,根据肾小管间质损伤程度分为轻中度组(57例)和重度组(32例)。另选择肾良性肿瘤患者的瘤旁组织10例为肾病理对照组。采用免疫组织化学法检测各组肾组织ZAG、转化生长因子β(transforming growth factor-β,TGF-β) 表达,采用酶联免疫吸附测定法检测尿液ZAG水平。分析ZAG表达水平与临床病理指标相关性。
〖HTH〗结果〖HTSS〗〖KG*2〗轻中度组和重度组糖化血红蛋白、体重指数、胆固醇、收缩压、舒张压、尿蛋白定量、肾小管间质损伤积分、尿ZAG均高于对照组,而肾小球滤过率(estimated glomerular filtration rate,eGFR)、白蛋白低于对照组(P<0.05);重度组尿蛋白定量、肾小管间质损伤积分、尿ZAG均高于轻中度组,eGFR低于轻中度组(P<0.05)。轻中度组与重度组糖化血红蛋白、体重指数、胆固醇、收缩压、舒张压、白蛋白差异均无统计学意义(P>0.05)。ZAG在对照组肾小管上皮细胞及肾间质中明显表达,在轻中度组肾小管间质表达较对照组降低,在重度组表达较轻中度组明显降低。糖尿病肾病肾组织ZAG表达水平与eGFR呈正相关,与尿蛋白定量、肾小管间质损伤积分及TGF-β表达呈负相关(P<0.05)。尿液ZAG水平与eGFR呈负相关,与肾小管间质损伤积分呈正相关(P<0.05)。
〖HTH〗结论〖HTSS〗〖KG*2〗糖尿病肾病患者肾小管间质ZAG表达降低,尿ZAG水平升高,均与肾小管间质损害程度相关;ZAG可作为评估肾间质纤维化程度的生物学指标。

关键词: 糖尿病肾病, 锌&alpha, 2糖蛋白, 肾小管间质

Abstract: [Abstract]Objective〖HTSS〗To investigate the expression of zinc alpha 2 glycoprotein(ZAG) in kidney tissue and urine of patients who had diabetic nephropathy(DN) and to analyze its relationship with clinicopathological parameters.
〖HTH〗〖WTHZ〗Methods〖HTSS〗Eighty-nine patients with diabetic nephropathy diagnosed by renal biopsy were included in this study. The patients were divided into two groups according to the degree of tubulointerstitial injury: the mild/moderate tubulointerstitial injury DN group(57 cases)and the severe tubulointerstitial injury DN group(32 cases). The distant renal tissues far away from the tumor tissue of patients with benign renal tumor were taken as control. The expression of ZAG, transforming growth factor-β(TGF-β) in kidney tissue was detected by immunohistochemistry and urine ZAG level was assessed by enzyme-linked immunosorbent assay. The correlation between ZAG expression and clinicopathological indexes was analyzed.
〖HTH〗〖WTHZ〗Results〖HTSS〗Compared with the control group, there was a significant increase of glycated hemoglobin A1c(HbA1c), body mass index(BMI), cholesterol, systolic blood pressure(SBP), diastolic blood pressure(DBP), urine protein excretion, tubulointerstitial injury score, and the urine ZAG level in mild/morderate DN group and severe DN group, but estimated glomerular filtration rate(eGFR) and albumin were lower than those in the control group(P<0.05). In the severe group , urine protein excretion, renal tubulointerstitial injury score and urine ZAG were higher and eGFR was lower than those in the mild/moderate group(P<0.05). There was no significant difference in HbA1c, BMI, cholesterol, SBP, DBP and albumin between the mild/moderate and severe groups(P>0.05). ZAG was obviously expressed in tubular epithelial cells and interstitium of the control group. The expression of ZAG decreased in the mild/moderate group and remarkably decreased in the severe group. The expression of ZAG in renal tubulointerstitium was positively correlated with eGFR and negatively correlated with 24-hour urinary protein, TGF-β expression and tubulointerstitial injury score(P<0.05). Urine ZAG level was negatively correlated with eGFR and positively correlated with tubulointerstitial injury score(P<0.05).
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗The expression of ZAG in renal tubulointerstitium decreased and the level of urine ZAG increased in patients with diabetic nephropathy, which are correlated with tubulointerstitial damage. ZAG may be used as an index to evaluate the degree of renal interstitial fibrosis.

Key words: diabetic nephropathies; zinc-α2-glycoprotein, tubulointerstitium