NF-κB抑制剂(PDTC)对大鼠抗胸腺细胞血清性肾炎系膜细胞凋亡、坏死及增生的影响  

Effect of the NF-κB inhibitor pyrrolidine dithiocarbamate on the apoptosis and proliferation of mesangial cells in the rat with anti-thymocyte serum nephritis

作　　者：徐静华[1] 王迎伟[1] 徐娟[1] 吴宜琴[1] 佟建霞[1] 孙彬[1] 

机构地区：[1]南京医科大学微生物与免疫学系,江苏南京210029

出　　处：《中国病理生理杂志》2005年第7期1305-1310,共6页Chinese Journal of Pathophysiology

基　　金：江苏省教育厅自然科学基金重点课题(No.03KJA310074);南京医科大学创新基金资助项目(No.CX2003007);南京医科大学校发展基金资助项目(NY03064)

摘　　要：目的:研究吡咯二硫氨基甲酸脂(PDTC)作为NF-κB核转录因子特异性抑制剂对大鼠系膜增生性肾炎,即抗胸腺细胞血清性肾炎(ATSN)系膜细胞(MC)凋亡、坏死及增生病变的影响。方法:利用兔抗大鼠胸腺细胞抗血清(ATS)复制大鼠ATSN模型,并将大鼠设为3组,即ATSN模型组、ATSN+PDTC处理组和正常对照组。实验40min、24h和7d分别取各组大鼠肾皮质切片用末端转移酶介导的dUTP缺口末端标记(TUNEL)技术和光镜、电镜、免疫组化方法检查其肾小球内NF-κBp65的表达和MC凋亡、坏死及增生病变。结果:ATSN模型组实验40min时肾小球内NF-κBp65即开始表达,与对照组之间有显著差别(P<0.01),24h表达进一步增多,第7d时达到较高水平。而ATSN+PDTC处理组7d时,不仅肾内NF-κBp65的表达明显低于ATSN模型组,且肾小球MC的增生及细胞外基质(ECM)的分泌也低于ATSN模型组,但用PDTC处理对ATSN大鼠其早期(40min及24h)MC的病变无抑制效应。结论:NF-κB特异性抑制剂PDTC对ATSN大鼠的肾小球继发增生病变有抑制作用。AIM: To explore the effect of pyrrolidine dithiocarbamate (PDTC), the specific inhibitor of NF-κB, on anti-thymocyte serum nephritis (ATSN) in rats. METHODS: The rat model of ATSN was reproduced with rabbit anti-thymocyte serum (ATS). The rats were divided into ATSN group, ATSN+PDTC group and control group. The expression of NF-κB p65 and the apoptosis, lysis as well as proliferation of mesangial cells (MC) were examined by immunohistochemical staining, Tdt-mediated X-dUTP nick end labeling (TUNEL), light microscope and electron microscope at 40 minutes, 24 hours and 7 days after injection of ATS or normal serum. RESULTS: The expression of glomerular NF-κB p65 in the ATSN group was observed with significant difference compared to controls at 40 min (P<0.01), it was elevated more at 24 hours, and was significantly increased at day 7, but the expression of NF-κB p65 in ATSN+PDTC group was less than that in ATSN group. The proliferation of glomerular MC and the secretion of extracellular matrix (ECM) in ATSN group were less than those in ATSN+PDTC group on day 7. PDTC had little role in the pathologic changes of rats in ATSN group in early stage (40 min and 24 hours), but affected the MC proliferation. CONCLUSION: PDTC, an inhibitor of NF-κB, suppresses glomerular MC proliferation in rats with ATSN.

关 键 词：吡咯烷类 NF-KB 肾炎 细胞凋亡 

分 类 号：R363[医药卫生—病理学]