体外头孢曲松对人肾小管上皮细胞凋亡基因的影响

摘要

Objective To explore the effect of ceftriaxone on apoptosis genes in human renal tubular epithelial cells in vitro. Methods The human renal tubular epithelial cells were cultivated in vitro and their morphology was observed under in-verted microscope after stimulation with different concentrations of ceftriaxone. The expression levels of three apoptosis-related genes, p53, bcl-2 and c-Myc, were detected in human renal tubular epithelial cells stimulated with different concentrations of ceftriaxone. Results The morphology of human renal tubular epithelial cells had no obvious changes under microscope when they were stimulated with different concentrations of ceftriaxone (0, 20, 40, and 80 mg/L). There were signiifcant differences in expression levels of p53, bcl-2 and c-Myc genes among different concentrations of ceftriaxone (P<0.01). Compared with other three groups, in 80 mg/L group, the expression levels of p53 and c-Myc genes were signiifcantly increased and levels of bcl-2 genes were signiifcantly decreased (P<0.01). However, there was no difference in the expression levels of three apoptosis-related genes among 0, 20, and 40 mg/L groups (P>0.05). Conclusions High blood drug concentrations of ceftriaxone lead to increased expression of pro-apoptotic genes and decreased expression of anti-apoptotic genes, which may be one of the mechanisms caus-ing kidney damage.%目的：探讨头孢曲松对人肾小管上皮细胞凋亡基因的影响。方法体外培养人肾小管上皮细胞，以不同浓度头孢曲松刺激后，倒置显微镜观察人肾小管上皮细胞形态，荧光定量PCR法检测不同浓度头孢曲松作用下人肾小管上皮细胞中凋亡相关基因p53、bcl-2及c-Myc的相对表达量。结果以不同浓度的头孢曲松(0、20、40、80 mg/L)体外刺激人肾小管上皮细胞，光镜下细胞形态未见明显改变。p53、c-Myc和 bcl-2三个基因相对表达量在不同浓度头孢曲松的组间差异有统计学意义(P均<0.01)。与另外三组相比，80 mg/L组p53及c-Myc基因相对表达量升高，bcl-2基因相对表达量降低，差异有统计学意义(P均<0.01)；而0、20、40 mg/L三组间3个基因相对表达量的差异无统计学意义(P均>0.05)。结论头孢曲松在较高血药浓度下导致人肾小管上皮细胞促凋亡基因的表达增加，抑制凋亡基因的表达降低，这可能是临床头孢曲松引起肾损伤的机制之一。