细胞周期调控蛋白在乙型肝炎病毒相关性IgA肾病与原发性IgA肾病肾组织表达对比研究

A comparative study on expression of cell cycle regulatory proteins between patients with hepatitis B virus-associat-ed IgA nephropathy and primary IgA nephropathy

目的探讨细胞周期调控蛋白cyclinD1、p27及p57在乙型肝炎病毒相关性IgA肾病（HBV—IgAN）与原发性IgA肾病（plgAN）中肾组织表达变化及意义。方法以2008年1月至2010年7月在南京军区福州总医院并经肾穿刺活检病理诊断为HBV—IgAN患者29例、pIgAN患者32例为研究对象。采用免疫组化方法检测29例HBV—IgAN和32例plgAN患者肾活检组织中cyclinD1、p27及p57的表达情况，分析其与临床病理指标的关系。8例正常肾组织为对照。结果在正常肾组织的肾小球中cyclinD1呈微弱表达或不表达，p27及p57呈高表达。。随着病变加重，肾小球中cyclinD1逐渐上调，p27表达逐渐下调，两种疾病之间差异无统计学意义；与正常组相比，p57表达在plgAN11级组无明显变化，而HBV—IgAN11级组明显下调（P〈0．01），plgANBI～1V级和HBV—IgANm～IV级组表达最弱，差异无统计学意义。肾小球发生球囊粘连、硬化时cyclinD1表达上调，p27和p57表达均下调；伴新月体者肾小球p57的表达明显下调，而p27和cyclinD1无明显变化。肾小球p57表达在尿蛋白〉1．0g／24h组显著低于≤1．0g/24h组（P〈0．05），两种疾病之间差异无统计学意义。结论HBV—IgAN与plgAN中cyclinD1上调和p27下调促进肾小球病变的进展。足细胞p57表达下调在HBV—IgAN出现较早，促进蛋白尿的形成及新月体的形成。

Objective To compare the expression of cyclin D1 ,p27 and p57 protein between patients with hepatitis B virusassociated IgA nephropathy （HBV-IgAN） and primary IgA nephropathy （pIgAN）, and to investigate their roles in the progression of the diseases. Methods Renal biopsy specimens were collected from 29 cases with HBV-IgAN and 32 cases with plgAN, and the protein expression of cyclin D1 ,p27 and p57 were inspected by immunohistochemistry. Normal renal tissues were collected from nephrectomy serving as controls （n = 8 ）. Results In the control group, eyclin D1 protein was mildly expressed or not expressed while p27 and p57 proteins were highly expressed. However,the expression of cyclin D1 protein was up-regulated while the expression of p27 protein was down-regulated with progression of diseases both in HBV-IgAN and plgAN patients. Up-regulation of cyclin D1 protein and down-regulation of p27 protein were not significantly different between two diseases. Compared with that in the control group, the expression of p57 protein was not significantly different in pIgAN degree II subgroup but was down-regulated significantly in HBV-IgAN degree II subgroup （ P 〈 0. 01 ）. The expression of p57 protein was the lowest in the degree III - IV subgroup of both pIgAN and HBV-IgAN patients, and the expression levels were not significantly different between the two diseases. Cyclin D1 expression increased while p27 and p57 ex- pression decreased significantly at the presence of Bowman＇s capsule adhesion and glomerular sclerosis. P57 protein was expressed significantly lower in glomeruli of patients with crescent formation while p27 and cyclin D1 protein expression were not significantly affected. The glomerular expression of p57 protein was significantly lower （ P〈 0. 05 ） in patients with proteinuria 〉 1.0 g/24 h than that in patients with proteinuria ≤ 1.0 g/24 h both in pIgAN and HBV-IgAN patients and there was no significant difference between the two diseases. Conclusion Up-regulation of cyclin D1 protein and down-regulation of p27 protein may synergistically affect glomerular mesangial proliferation, Bowman＇s capsule adhesion and glomerular sclerosis. Compared with those in pIgAN patients, down-regulation of p57 protein expression appears earlier in HBV-IgAN patients, which may cause albuminuria and promote the formation of crescents in glomeruli.