常染色体显性遗传多囊肾病患者外周血淋巴细胞DNA的损伤

DNA damage in peripheral blood iymphocytes of patients with autosomal dominant polycystic kidney disease

目的研究常染色体显性遗传多囊肾病（ADPKD）患者及其家系成员外周血淋巴细胞DNA的损伤及辐射对其基因稳定性的影响。方法采用单细胞凝胶电泳技术（SCGE）研究10例ADPKD（A组）、1个ADPKD家系中3例无症状者（B组）、20例健康对照者（C组）外周血淋巴细胞的DNA损伤及在0．5Gy照射后的DNA损伤情况。采用彗星分析软件（CASP）进行图像分析，以尾DNA含量（TDNA％）评价淋巴细胞的DNA损伤程度。结果A组照射前、后TDNA％（8．85％±0．14％，14．84％±0．77％）及照射后TDNA％的增加值（6．00％±0．77％）均显著高于C组（7．50％±0．37％，12．46％±0．26％，4．96％±0．44％），B、C两组及A、B两组间差异无统计学意义。B组中1例TDNA％照射前后均显著高于C组。结论ADPKD患者外周血淋巴细胞具有基因不稳定性，在环境因素刺激下，有可能通过基因突变启动多脏器囊肿形成。SCGE为进一步阐明ADPKD发病机制及预后判断提供了一种新的方法和思路。

Objective To detect DNA damage of peripheral blood lymphocytes in patients and family members of autosomal dominant polycystic kidney disease （ADPKD）, and to study the effect of irradiation on genomic stability of lymphocytes. Methods Before and after 0.5 Gy radiation dose, single-cell gel electrophoresis （SCGE） was employed to analyze DNA damage of lymphocytes in 10 ADPKD patients （group A）, 3 members without clinical symptoms of a ADPKD family （group B） and 20 healthy control people （group C）. The damage was estimated based on the content of DNA in tail （TDNA%） with comet analysis software （CASP）. Results Both before and after irradiation, the TDNA% （8.85%±0.14%, 14.84%±0.77%） and the value-added （6.00%± 0.77%） of TDNA% of group A were significantly higher than those of group C （7.50%±0.37%, 12.46%±0.26%, 4.96%±0.44%） respectively. There were no significant differences between group B and group C or group A and group B. While 1 person in group B had higher TDNA% as compared to group C both before and after irradiation. Conclusions The lymphocytes of ADPKD patients are more sensitive to ionizing radiation as compared to healthy people. The genomic instability in ADPKD patients or member of ADPKD family may trigger cystic formation in multi-organs when exposing to environmental agents. SCGE may provide a new approach to elucidate the pathogenesis and prognosis of ADPKD.