外源性腐胺对正常大鼠肾功能和细胞凋亡的影响

Exogenous putrescine causes renal function impairment and cell apoptosis in rats

目的探讨一定浓度的外源性腐胺对肾功能及对细胞凋亡的影响。方法采用健康SD大鼠90只,完全随机分为正常对照组(N组)共10只,外源性腐胺注射组(P组)80只,其中P组设P1组和P2组两个腐胺剂量亚组,每亚组各40只。N组和P1、P2组分别于腹腔内一次性注射生理盐水和50、25μg·g^(-1)两种腐胺剂量稀释液各2 ml,注射后24、48、72、96 h四个时相点各组活杀10只,心脏采血测定血清中Cr、BUN的含量,摘取肾器官制作组织切片HE染色后光镜下观察组织形态学改变,TUNEL法检测肾细胞凋亡,对比分析这两组的异同。结果 (1)P组大鼠各亚组光镜下见肾组织少部分有轻度的水肿,无明显的细胞坏死;(2)P1和P2两亚组的Cr、BUN含量与N组比较存在差异,呈不同程度升高(F=15.135-58.644,P<0.01;F=5.71-29.28,P<0.01);两亚组组内不同时相点Cr、BUN含量也分别存在差异并出现不同程度升高(F=18.59-18.93,P<0.01;F=3.19-5.84,P<0.05)。(3)P1和P2亚组肾组织中凋亡细胞逐渐增多,分别在96 h和48 h时相点达到峰值。与N组比较,P1组96 h肾细胞凋亡率[(24.78±2.19)%vs(4.47±0.33)%,P<0.01],P2组48 h肾细胞凋亡率[(26.27±2.13)%vs(4.47±0.33)%,P<0.01]。结论一定浓度的外源性腐胺能导致肾功能不同程度的损害,可诱导肾细胞异常凋亡;细胞凋亡程度和肾功能损害可能与血中腐胺浓度存在关联。

Objective To explore the effect of exogenous putrescine on renal function and cell apoptosis in rats. Methods Ninety SD rats were randomized into control group （n=10）, high-dose putrescine group （P1 group, n=40）, and low-dose putrescine group （P2 group, n=40） with intraperitoneal injections of 2 ml of normal saline, 50 μg/g putrescine, and 25 gg/g putrescine, respectively. At 24, 48, 72 and 96 h after the injections, 10 rats from each group were sacrificed to examine serum Cr and BUN levels, histological changes in the kidneys, and renal cell apoptosis （TUNEL assay）. Results The rats in the two putrescine- treated groups showed mild edema in some renal tissues without obvious necrosis. In P1 and P2 groups, serum Cr and BUN levels differed significantly at each time point of measurement （P〈0.01 and P〈0.05, respectively）, and were significantly higher than the levels in the control group （P〈0.01 and P〈0.05, respectively）. The two putrescine-treated groups showed gradually increased renal cell apoptosis with time, reaching the peak levels at 96 h and 48 h, respectively. The peak renal cell apoptosis rates in P1 [（24.78±2.19）%] and P2 [（26.27±2.13）%] group were significantly higher than the rate in the control group [（4.47±0.33）%, P〈0.01]. Conclusion Exogenous putrescine can lead to renal function impairment and induce renal cell apoptosis in rats, and the severity of these changes appeared to be associated with the blood concentration of exogenous putrescine.