纳米氧化铝对大鼠肝组织细胞促凋亡作用研究

Apoptosis of rat liver cells induced by nano-aluminum oxide

目的:纳米氧化铝(NAOs)是广泛应用的纳米材料,通过比较NAOs颗粒及非纳米氧化铝(nNAOs)颗粒对大鼠肝脏的影响研究其潜在的毒性作用。方法:将60只SD大鼠随机分为生理盐水对照组、50mg/kgNAOs组、50mg/kgnNAOs组,每组20只,隔日腹腔注射1次,共60d。采用原子吸收分光光度法测定铝元素在肝组织中含量的变化;免疫组织化学染色观察肝组织中枯否细胞(Kupffercells)的活化;RT-PCR检测凋亡相关基因Bax及Bcl-2mRNA表达的改变。结果:NAOs组大鼠肝脏中铝元素的浓度在染毒第4日达到峰值后逐渐降低,而nNAOs组大鼠肝脏中铝元素的浓度随染毒时间的延长而逐渐升高,两组大鼠均观察到枯否细胞的活化。nNAOs组Bax/Bcl-2比值为1.78,NAOs组为3.59,均显著高于对照组1.0(P均<0.05),且NAOs组与nNAOS组间的差异有统计学意义(P<0.05)。结论:NAOs及nNAOs均能引起大鼠肝组织中枯否细胞活化,但NAOs引起肝组织细胞凋亡的程度高于nNAOs,可能与两种不同粒径的氧化铝在肝组织的代谢特征不同有关。

OBJECTIVE：Nano aluminum oxide （Al2 O3） is used widely, so there is an urgent requirement to study the toxic effects of nano Al2 O3 to rat livers. METHODS： 60 SD male rats were randomly divided into 3 groups（20 per group）： control group, 50 mg/kg non-nano-Al2 O3 group（nNAOs）and 50 mg/kg nano-Al2O3 group（NAOs）. Each group was treated by intraperitoneal injection once every two days. The accumulation and metabolism of Al was analyzed by atomic absorption spectrum（AAS）, expression of ED-1 by Kupffer cell was analyzed by immunohistochemistry. RT-PCR was used to analyze the expression of apoptosis-related genes, Bax and Bcl-2. RESULTS： The peak concentration of NAOs in liver appeared on the 4th day, however, the concentration of nNAOs increased during the observation period. Activities of Kupffer cells were observed in both groups. The ratios of Bax/Bcl-2 in non-nano and NAOs were 1.78 and 3.59, respectively, with significant difference（P0.05） and were significantly increased when compared with control group（P0.05）. CONCLUSION： Nano- and non-nano-Al2 O3 could induce the activities of Kupffer cells in rat livers. However, apoptosis induced by NAOs increased significantly than that induced by nNAOs, which may be related to the metabolism characteristics of the two Al2 O3 particles in rat livers.