阿昔洛韦诱导的人肾小管上皮细胞NGAL、IL-18表达及其意义

Expression and significance of NGAL and IL-18 induced by acyclovir in human renal tubular epithelial cells

目的观察不同浓度阿昔洛韦诱导的体外培养人近端肾小管上皮细胞(HK-2)的形态变化、IL-18、NGAL的表达及其意义。方法将正常培养的HK-2细胞分组:1正常组;22μg/ml阿昔洛韦组;33μg/ml阿昔洛韦组(模型组)。各组干预12 h后,倒置显微镜下观察各组细胞状态、细胞数量变化,逆转录-聚合酶链式反应法(RT-PCR)检测各组细胞IL-18、NGAL基因表达水平,Western-blotting法检测各组IL-18、NGAL蛋白表达。结果12μg/ml阿昔洛韦及3μg/ml阿昔洛韦组,细胞生长与正常组比较无差异,但细胞形态异常;2在mRNA水平,模型组干预后,IL-18水平明显增高,NGAL水平明显增高,与正常组比较P<0.01;与蛋白水平表达方面类似。结论阿昔洛韦对HK-2细胞的生长有浓度依赖性抑制作用;高浓度的阿昔洛韦可导致HK-2细胞结晶,低浓度阿昔洛韦诱导的肾小管上皮细胞损伤伴有NGAL、IL-18的异常表达和分泌,对临床早期监测阿昔洛韦所致急性肾损伤有重要意义。

Objective To observe the effect of different concentrations of acyclovir（ACV） on the morphological changes of cultured human renal proximal tubular epithelial ceils （ HK-2 ） , and study the expression and significance of Neutrophil gelatinase-assoeiated lipocalin（NGAL） and IL-18 in HK-2 cells. Methods The cultured HK-2 cell were divided into normal group,2μg/ml acyelovir group and 3μg/ml aeyelovir group（ model group）. 12 hours after the intervention, the number and state of cells were observed under inverted microscope;the expressions of IL-18 and NGAL gene were detec- ted by reverse transcriptase polymerase chain reaction（RT-PCR） ,and the level of IL-18 and NGAL protein was detected by Western-blotting method. Results （1）As compared with the normal group,cells in the 2 μg/ml acyclovir group and 3 μg/ml aeyelovir group grew well, but their shapes were abnormal. （2）The all expression of mRNA and protein of IL-18 and NGAL increased obviously in the model group as compared with the normal group （ P 〈 0.01 ）. Conclusion The growth inhibiting of aeyclovir on HK-2 cells showed a concentration dependent, the high concentration acyclovir can lead to the crystallization of HK-2 cell,while the low concentration aeyclovir can induce renal tubular epithelial cell injury and the abnormal expression and secretion of IL-18 and NGAL. This result has important significance for clinical early detection of acute renal injury induced by Acyelovir.