热休克蛋白73在中毒性急性肾小管坏死动物模型中的表达及其意义

Expression and Singnificance of 73 - kilodalton Heat Shock Protein in the Animal Model of Toxic Acute Tubular Necrosis

目的 观察热休克蛋白73(HSP73)在庆大霉素(GM)诱发的中毒性急性肾小管坏死动物模型中的表达并探讨其意义。方法 给成年Wistar大鼠皮下注射(GM400mg/kg·day)2d,对照组用生理盐水。在首次注射GM后不同时相点,观察尿量(UV)、尿蛋白(UP)、血肌苷(Cr)、血尿素氮(BUN)、肌苷清除率(CCr)、及钠排泄分数(FENa),同时,用免疫组织化学方法检测紧组织中HSP73的分布及强度。结果 在使用GM后,UV、UP、Gr、BUN和 FENa增加,但 CCr降低。HSP73从胞核弥散至胞浆中,并以颗粒的形式积聚于近曲小管上皮细胞中。这些颗粒于首次注射GM后12h出现,表达增强直至第2d,第5d已减少,但第8d时又增强,第11d完全消失。结论(1)HSPs可作为急性肾中毒损伤的最早标志之一。(2)HSPs可能发挥细胞保护作用。

Objective To observe the expression of 73 -kilodalton heat shock protein (HSP73)in the animal model of gentamicin-induced toxic acute tubular necrosis and approach its significance. Methods Adult Wistar rats received subcutaneous injection of gentamicin (400mg/kg· day)for 2 days,While control animals received physiologic saline. At the different time point after the first gentamicin exposure, the urine volume (UV) , urine protein (UP), serum creatinine(Cr) , blood urea nitrogen (BUN),creatinine clearance (CCr) and fraction of Na excretion (FENa) were observed. Meanwhile, the distribution and intensity of HSP73 were examined immunohistochemically. Results After the gentamicin injection,UV,UP,Cr,BUN,and FENa increased,but CCr decreased. HSP73 translocated from the nucleus to the cytoplasm and accumulated in granules in the proximal tubular epithelial cells. These granules started to appear from 12h after the first gentamicin exposure, increasingly expressly until day 2,and diminished at day 5,but increased again at day 8. By day 11,the HSP73 granules disappeared completed. Conclusion (1)HSPs may act as one of the earliest indicators of acute nephrotoxicity. (2)HSPs may play a role in the cytoprotection.