尿本周蛋白促进肾小管上皮细胞凋亡的体外研究

In vitro investigation on the Bence-Jones protein on the apoptosis of the renal proximal tubular cells

多发性骨髓瘤(MM)患者尿本周蛋白(BJP)对肾近端小管上皮细胞(PTC)具有直接毒性,本研究通过体外观察BJP对PTC的凋亡作用以探讨BJP对PTC的部分毒性机制。将自MM患者尿中提取并经免疫固定法琼脂糖凝胶电泳进行鉴定的4例κ和λ型BJP以不同浓度与大鼠NRK52E株PTC共同培养12～48h,用原位末端标记法、流式细胞仪及透射电镜检测凋亡。结果显示:①BJPκ组与BJPλ组BJP为10mg/ml与20mg/ml时诱导PTC凋亡的比例明显高于对照组及5mg/ml,两组诱导PTC凋亡的比例随着培养时间的延长而显著增加且明显高于空白对照组;②BJPκ组与BJPλ组之间诱导PTC凋亡的比例无明显差异。结果表明,κ与λ型BJP均可诱导PTC凋亡,且随着BJP浓度及培养时间增加而增强。

The Bence-Jones protein （BJP） in the urine of patients with multiple myeloma （MM） shows direct toxicity on the renal proximal tubular cells （PTC）. In the present study, an in vitro study on the mechanism for the partial toxicity of BJP on the renal PTC was made. In this study, the effects of k and λ types of BJP on the rat NRK,52E PTC cultivated for 12-48 hours were observed by flow cytometry, TUNEL and eleetron-micrography. The results showed that the apoptotic rates of the PTC co-cultured with 10 mg/ml and 20 mg/ml were higher than those co-cultured with 5 mg/ml of BJP in both the BJP group and control group. The proportions of apoptosis induced in both groups significantly increased keeping pace with advance of times, and were comparatively higher than those of the control group. However, there was no significant difference in the apoptotie rates k or λ type of BJP groups. These results indicate that both the k and λ types of BJP show anti-proliferative effect and can induce apoptosis of rat renal proximal tubular cells in vitro, and this effect enhances with concentration of BJP and the times of co-cultivation.