Supperssion of the Activation of Nuclear Factor Kappa B and the Expression of Monocyte Chemoattractant Protein-1 by Glucocorticoids in Experimental Rat Glomerulonephritis
ZHANG Ai-Hua, CHEN Rong-Hua, HUANG Song-Ming, XING Chang-Ying, LIN Na, FEI Li, GUO Mei, PAN Xiao-Qin, CAI Yi
Center of Pediatric Nephrology, Nanjing Medical University, Nanjing 210029, China
摘要 目的：探讨核因子-κB(NF-κB)活化在肾小球肾炎发病机制中的作用及糖皮质激素对NF-κB活化的调节作用。方法：肾毒血清肾炎应用兔抗鼠肾小球基底膜肾毒血清制备。模型组：注射肾毒血清后不加任何治疗，第14 d处死；糖皮质激素干预组(治疗组)：于肾毒血清注射后第1～14 d给予地塞米松每日0.125 mg/kg腹腔注射。采用免疫组化及医学图像分析系统观察肾小球及肾小管中NF-κB活化和单核细胞趋化蛋白-1(MCP-1)的表达，并分析其与蛋白尿和肾小球细胞数之间的关系。结果：模型组肾小球及肾小管中NF-κB活化较正常对照组显著上调，分别为(38.27±8.83)% vs (1.82±0.68)%和(68.46±12.94)% vs (16.89±4.47)%，P均<0.01；模型组肾小球及肾小管中MCP-1表达分别为(24.37±7.06)个/gcs和(54.78±11.49)%，较正常对照组显著升高(P<0.01)，肾小球中NF-κB活化和MCP-1表达与单核细胞浸润和蛋白尿密切相关；糖皮质激素干预组肾小球及肾小管中NF-κB活化和MCP-1表达均显著下调。结论：NF-κB活化在肾小球肾炎发病机制中发挥重要作用，抑制NF-κB活化可能是糖皮质激素抗肾炎作用的机制之一。
Abstract：OBJECTIVE: To investigate the role of nuclear factor kappa B (NF-κB) in the pathogenesis of glomerulonephritis and to determine whether glucocorticoids can inhibit the activation of NF-κB in vivo. METHODS: Nephrotoxic sera nephritis (NTN) was induced by the injection of antiGBM antibody into the tail veins of rats. Glucocorticoidtreated rats received dexamethasone (0.125 mg/kg weight) daily for 14 days. Untreated and steroidtreated rats were killed on day 14 and NF-κB activation and monocyte chemoattractant protein1 (MCP-1) expression were assessed in glomerulus and renal tubules of rats. RESULTS: Significant upregulation of NF-κB activation was observed in glomerulus and renaltubules of untreated NTN rats compared to the control group ［(38.27±8.83)% vs (1.82±0.68)%; (68.46±12.94)% vs (16.89±4.47)%, repsectively］ (P<0.01), and so was the expression of MCP-1 ［(24.37±7.06) cells/gcs vs 0; (54.78±11.49)% vs (11.26±6.88)%］ (P<0.01). NF-κB activation and MCP-1 expression were associated with monocyte cell infiltration and the degree of proteinuria. Significant downregulation of NF-κB activation and MCP-1 expression were observed in the glucocorticoidtreated rats. CONCLUSIONS: The activated NF-κB may play a pivotal pathogenic role in glomerulonephritis and the antinephritic action of glucocorticoids may be mediated through the suppression of the activation of NF-κB.
ZHANG Ai-Hua,CHEN Rong-Hua,HUANG Song-Ming et al. Supperssion of the Activation of Nuclear Factor Kappa B and the Expression of Monocyte Chemoattractant Protein-1 by Glucocorticoids in Experimental Rat Glomerulonephritis[J]. CJCP, 2001, 3(2): 166-169.
