幼年大鼠静脉注射头孢曲松钠与口服钙剂相互作用的研究

目的 探讨静脉注射头孢曲松钠与口服钙剂能否联用，观察对幼年大鼠肾功能与组织结构的影响，为婴幼儿的合理用药提供依据。方法 取SD幼年大鼠80只，随机分成8组，每组10只。钙+头孢曲松钠高、中、低剂量组：先用800mg/kg CaCl2灌胃，然后尾静脉分别注射600、400和200mg/kg的头孢曲松钠。空白对照组：尾静脉给予生理盐水；头孢曲松钠高、中、低阳性对照组：尾静脉分别注射600、400和200mg/kg的头孢曲松钠；钙剂对照组：800mg/kg CaCl2灌胃。连续给药7d，7d后处死大鼠，组织病理学检测肾脏的微观形态；检测肾生化指标Cr、BUN；使用ELISA检测大鼠早期肾功能的指标：胱抑素C(CysC)、β2-微球蛋白(β2-MG)、视黄醇结合蛋白(RBP)[1]。结果 病理切片显示高剂量头孢曲松钠+钙组、高剂量头孢曲松钠阳性对照组镜下肾小管有结晶，并伴不同程度的淋巴细胞浸润、肾小管上皮细胞水肿；而中剂量头孢曲松钠+钙组出现了肾小球充血；此外，中剂量头孢曲松钠+钙组、中剂量头孢曲松钠阳性对照组也出现了肾小管上皮细胞水肿。肾功能生化指标Cr、BUN与空白对照组、钙剂对照组相比，各组间无明显差异。经单因素方差分析，与空白对照组、钙剂对照组相比，CysC、β2-MG、RBP指标组间差别有统计学差异(P<0.05)，经LSD法两两比较，钙剂+高、中剂量头孢曲松钠组，高剂量头孢曲松钠阳性对照组与空白对照组、钙剂对照组相比，CysC、β2-MG、RBP指标有统计学差异(P<0.05)。钙剂+低剂量头孢曲松钠组RBP与空白对照组相比，差别有统计学差异(P<0.05)。结论 两者联用可造成早期肾功能及病理损害。

Study on the interaction between intravenous ceftriaxone sodium and oral calcium agent in juvenile rats

Objective To explore whether ceftriaxone sodium and oral calcium supplements used in combination can result in kidney damage much easier and lead to much higher incidence of nephrolithiasis in juvenile rats. The results can provide evidence for infant rational drug use. Methods 80 Sprague-Dawley juvenile ratswere randomly divided into eight groups with ten individuals in each group. calcium+ceftriaxone sodium groups were treated with 800mg/kg CaCl2 by the route of lavage firstly. Then, rats were injected 600, 400 and 200mg/kg ceftriaxone sodium by the route of tail vein respectively. Vehicle controls were treated with saline. Positive controls were injected 600, 400 and 200mg/kg ceftriaxone sodium respectively. The calcium group was treated with 800mg/kg CaCl2 only. All the drugs were continuously delivered within seven days. All rats were sacrificed on day seven.Kidney histological examinations were performed. Cr and BUN were measured. β2-microglobulin (β2-MG), retinol binding protein (RBP), and Cystatin C (CysC) which can reflect changes of renal function were determined by ELISA[1]. Results Histological examination using HE staining demonstrated crystal formation in the ceftriaxone sodium high dose+calcium group and the high dose ceftriaxone sodium positive control group accompanied by lymphocyte infiltration with different extent and tubular epithelial cell edema. Glomerular congestion appeared in the middle dose ceftriaxone sodium+calcium group. In addition, there was also tubular epithelial cell edema in the middle dose ceftriaxone sodium+calcium group and the middle dose ceftriaxone sodium positive control group. There were no significant differences in Cr and BUN compared with the saline group and the calcium group respectively. There were significant differences in CysC, β2-MG, and RBP by one-way ANOVA, (P<0.05). With LSD comparison, there were significant difference in CysC, β2-MG and RBP in the calcium+high dose, the medium dose ceftriaxone sodium group and the high dose ceftriaxone sodium group compared with the saline group and the calcium group respectively (P<0.05). RBP in the calcium+low dose ceftriaxone sodium group was significantly different from that in the saline group (P<0.05). Conclusion Intravenous ceftriaxone sodium combined with oral calcium supplements tended to cause pathological damage to kidneys and damage to early renal