摘要
目的观察糖尿病肾病（DN）患者肾小管上皮细胞NF—κB及炎性介质表达的临床病理意义。方法选择经肾活检确诊的23例糖尿病肾病患者肾组织为DN组，以免疫组化法检测肾组织NF—κBp50、p65、单核细胞趋化蛋白（MCP）1、骨调素（OPN）等炎性介质及纤连蛋白（FN）、d平滑肌肌动蛋白（Ot—SMA）表达；原位杂交法检测NF—κBp65mRNA表达，并进行半定量评分；选择10例肾癌切除术患者为对照组，取离癌组织大于5cm处肾皮质，检测指标同DN组。采用Spearman等级相关法分析炎性介质表达与小管问质病理改变、尿N-乙酰-β-氨基葡萄糖苷酶（NAG）、尿蛋白量（24h）、肾小球滤过率（eGFR）之间的相关性。结果组织学检查显示，各期DN组患者多存在明显的肾小管上皮细胞变性、灶状萎缩、问质炎性细胞浸润及纤维化。免疫组化与原位杂交结果显示，对照组患者NF—κB、OPN和MCP-1在肾组织无明显表达，FN主要表达于肾小球，α-SMA主要表达于肾血管；DN组患者随着尿白蛋白水平的增加，NF—κB、OPN和MCP-1在肾小管表达显著增加，主要表达于结构相对正常的小管上皮细胞，在炎性细胞大量聚集及明显纤维化处表达较少；同时，肾间质α-SMA、FN表达也有明显增加，但主要表达于炎性介质阳性表达的小管周围及炎性细胞浸润与纤维化较明显的肾间质，二者均不表达于肾小管上皮细胞。相关分析显示，DN组患者肾小管NF—κBp65蛋向的表达与NF—κBp50蛋白、p65mRNA表达呈正相关，，分别为0．792和0．763，均P〈0．01；与肾小管MCP-1、OPN表达呈正相关,r分别为0．825和0．869，均P〈0．01；与间质α-SMA、FN表达呈正相关，r分别为0．327和0．432，均P〈0．01；与尿蛋广1量（24h）、eGFR、尿NAG水平均相关，r分别为0．710、-0．728、0．930，均P〈0．01。结论DN患者肾小管NF—KB及多种炎性介质表达明显上调，多分布于结构相对正常的肾小管上皮细胞。NF-κB及炎性介质的表达与蛋白尿、肾功能下降及肾间质纤维化等临床及病理表现密切相关，提示它们可能参与了人类DN的发生和发展；
Objective To investigate the expression of inflammatory mediators in renal tubular epithelial cells in patients with diabetic nephropathy （DN） and to explore the possible clinicopathological significance. Methods Twenty-three patients with DN diagnosed by renal biopsy and 10 patients with renal cell carcinoma undergone nephrectomy were allocated into DN group and control group, respectively. The renal expression of NF-κB p50, NF-κB p65, NF-κB p65 mRNA, MCP-1, OPN, α-SMA, and FN was detected by immunohistochemical or in situ hybridization assay. Serum creatinine, urinary N-acetylglucosaminedase （NAG）, urinary albumiu and 24-hour urinary protein were detected. The correlation between these inflammatory markers and clinicopathological data were analyzed. Results （1）Among all the 23 DN patients, granular degeneration of the renal tubular epithelium, focal tubular atrophy, infiltration of inflammatory cells and interstitial fibrosis were apparent, and none of these were found in control group. （2） Immunohistochemical and in situ hybridization assay showed that, compared with control group, expression of these factors increased significantly in renal tubular cells or interstitium in DN patients, and expression of ct-SMA or FN was not found in tubular epithelial cells. （3）Statistics assay showed the tubular NF-κB p65 protein expression was correlated with all of the following factors： NF-κB pSO protein （r=0.792） and NF-κB p65 mRNA （r=0.763）, tubular MCP-1 （r=0.825） and OPN （r=0.869） expression, interstitial ct-SMA （r=0.327） and FN （r=0.432） expression, proteinuria（r=0.710）, estimated glomerolar filtration rate （eGFR） （r=-0.728）, and urinary NAG （r= 0.930）, P〈O.01 respectively. Conclusion Tubular inflammation may play a role in the pathogenesis and progression of DN.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2010年第1期15-19,共5页
Chinese Journal of Nephrology
基金
国家自然科学基金（30800529）
天津市卫生局科研基金项目（2000KY02）
关键词
糖尿病肾病
NF-κB
肾小管
炎性介质
Diabetic nephropathies
NF-KB
Kidney tubules
Inflammation mediators
