血管内皮生长因子及其受体在乙型肝炎病毒相关性肾炎中表达及其意义研究

Expression and significance of vascular endothelial growth factor and its receptor in patients with Hepatitis B virus-associated nephritis

目的探讨血管内皮生长因子(VEGF)及其受体Ⅱ(Flk-1)和血栓调节蛋白(TM)在乙型肝炎病毒相关性肾炎(HBV-GN)中的表达情况,以及它们在疾病进展中的作用。方法以南京军区福州总医院经肾活检确诊的68例HBV-GN患者为研究对象,以8例行肾脏切除的肾脏肿瘤患者的正常肾组织为对照组,采用免疫组化方法检测肾活检组织中VEGF、Flk-1和TM的表达情况,分析其变化与临床病理指标的关系。结果 VEGF和Flk-1在HBV-GN中的表达均明显高于正常对照组,随着肾小球病变程度的加重,VEGF、Flk-1及TM的表达逐渐减少,在重度病变组表达最少(P<0.01)。硬化组中肾小球内VEGF和TM的表达呈正相关(r=0.701,P<0.05)。结论 VEGF及其受体在HBV-GN的进展中发挥重要作用,在病变早期可能上调,促进蛋白尿形成,而病变严重者则表达下降,影响血管生成再生,导致细胞外基质合成增多。

Objective To observe the expression of vascular endothelial growth factor（ VEGF）, Flk-1 and TM in hepatitis B virus associated nephritis （ HBV-GN）, and explore their roles in the progress of HBV-GN. Methods The clinical profiles of 68 renal biopsy-diagnosed patients with HBV-GN enrolled from Fuzhou General Hospital of Nanjing Military Area Command were retrospectively analyzed. The expression of VEGF, Flk-1 and TM was determined by means of immunohistochemistry assay, and the correlation between changes in expression levels and clinical pathologic indices was assessed. Results Patients with HBV-GN were associated with significantly increased expression of VEGF and Flk-1 compared with normal con- trois. The expression of VEGF, Flk-1 and TM showed a trend towards reduction following increased disease severity and apeared most impressively suppressed in the subgroup with most severe lesion （P 〈 O. 01 ）. In group SGN, the expression of Flk-1 ,VEGF and TM was considerably suppressed and the latter two were positively correlated （r = 0. 701, P 〈 0. 05 ）. Conclusion VEGF and its receptor play an important role in the development of HBV-GN via facilitating formation of proteinuria by means of up-regulation at the early stages yet resulting in angiogenesis and increased extracellular matrix synthesis by means of down-regulation in severe cases.