肾活检组织中NEP的表达及其与尿NEP含量之间的相关性研究

Expression of Neutral Endopeptidase(NEP) in Renal Tissue and Its Relationship with Urinary NEP

目的 观察肾活检组织中NEP的表达,研究它与尿NEP含量之间的关系,以期探讨检测尿NEP的临床意义。方法 将研究组分为对照组(n=100),肾小球疾病组(n=31)、急性肾小管损伤组(n=44)、慢性肾小管损伤组(n=61)、慢性肾功能衰竭组(n=13)。收集各组病人晨尿,然后通过荧光光谱分析,得到尿中NEP的量,并用相应尿肌酐值予以标化。同时对病人组中的68例患者的肾组织切片用免疫组化的方法进行染色,直接观察NEP的在肾组织中的表达情况,且进行其表达量与尿NEP的相关性研究。结果 正常对照组尿NEP为68.41ug/mmol Cr,急性肾小管损伤组尿NEP196.36ug/mmol Cr,明显高于正常对照组(P=0.0001),慢性肾小管损伤组、肾小球疾病所致的CRF组尿NEP分别为31.98、19.40ug/mmol Cr,均明显低于正常对照组(P均<0.01),而单纯肾小球疾病组尿NEP为75.49ug/mmol Cr,与正常对照组无差异(P=0.1425)。在急性肾小管损伤组和慢性肾小管损伤组,尿NEP与肾组织中NEP的表达均呈正相关,而肾小球疾病组内尿NEP与肾组织中NEP的表达无明显相关性。结论 肾小管刷状缘上NEP的表达量与近端小管损伤有良好相关性,尿NEP量实际反映近端小管刷状缘损伤情况。本研究在国内率先建立了尿NEP的检测方法,并用于临床研究。对尿中NEP的检测,提供了一种快速。

Objective To observe the expression of NEP in renal tissue and its relationship with urinary neutral endopeptidase in order to determine the clinical meaning in measuring urinary NEP. Methods We divided all persons in our study into live groups: control group (n = 100) .acute tubular injury group ( n - 44), chronic tubular injury group(n = 61), glomerular diseases group(n = 31) , chronic renal falure group(n = 13) . Urinary neutral endopeptidase enzymatic activty was spectrofluorimetrically measured, using a synthetic peptidic substrate. At the same time, NEP was detected by immunohistochemistry and the expression ot NEP in renal tissue and its relationship with urinary neutral endopeptidase was investigated.Results The NEP value of control group is 68.41ug/mmol Cr, The NEP value of acute tubular injury group(196.36 ug/ mmol Cr) is higher than that of nomal control (P = 0.0001) , while the value of chronic tubular injury group(31.98 ug/ rnmol Cr) and chronic renal failure group (19.40ug/ mmol Cr) is much lower than that of normal control(P < 0. 01) . The NEP value of glomerular disease group (75. 49 un/mmol Cr) has no significant difference from that of nomal control(P = 0. 1425) .In acute tubular injury group and chronic tubular injny group, the expression of NEP has significant positive correlation with urinary NEP. Hut in glomerular disease group there is not any correlation between them. Conclusions The expression of NEP in renal tissue had significant positive correlation with unary NEP of acute tubular injury group and chronic tubular injury group. The level of urinary NEP reflected the degree of injury of proximal renal tubule. In acute tubular injury patients, their urinary NEP increased much but in chronic tubular inujry patients, the urinary NEP decreased significantly. As a result, the measurement of urinary NEP will be helpful in diagnosing tubular injury.