海扇壳源性碳酸钙纳米微粒对大鼠的急性毒性作用

目的：观察海扇壳源性碳酸钙纳米微粒（CCNPs）对SD大鼠的毒性作用，初步探讨CCNPs的安全剂量和生物学效应。方法：将40只健康雄性SD大鼠随机分为对照组，低、中和高剂量CCNPs组（分别给予剂量0、30、60和120 mg·kg^-1 CCNPs），每组10只大鼠。尾静脉注射给药每天1次，连续14 d。检测各组大鼠体质量和日平均进摄食量、血液学指标、血清生化指标、器官相对质量及主要器官的组织病理形态表现。结果：在14 d重复剂量的毒性试验中，高剂量组中有2只大鼠死亡，而在低和中剂量组中均未发现有大鼠死亡。各剂量CCNPs组大鼠体质量增加幅度和日平均进食量低于对照组，但差异无统计学意义（P>0.05）。各剂量CCNPs组大鼠血清学指标与对照组比较差异无统计学意义（P>0.05）。各剂量CCNPs组大鼠肺脏相对质量高于对照组（P<0.05）；低和中剂量CCNPs组大鼠脾脏相对质量高于对照组（P<0.05）；高剂量CCNPs组大鼠脾脏相对质量与对照组比较差异无统计学意义（P<0.05）。低剂量CCNPS组大鼠部分脏器呈轻度的炎性浸润，未发现明显的病理学改变；中和高剂量CCNPs组大鼠主要脏器呈明显的组织病理学改变，包括炎性细胞浸润，肝细胞排列轻度紊乱，肝细胞空泡增多，肺泡间质增厚及大量肉芽肿形成，心肌纤维肿胀、断裂甚至坏死，肾小球出现萎缩和裂隙等。结论：小剂量CCNPs静脉给药不会引起大鼠严重的急性毒性反应。

Acute toxicity of cockle shell-derived calcium carbonate nanoparticles on rats

Objective:To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles (CCNPs) on the SD rats, and to preliminarily explore the safe dose and biological effects of CCNPs. Methods:A total of 40 healthy male SD rats were randomly divided into control group, low, middle and high doses of CCNPs groups (given 0, 30, 60, and 120 mg·kg^-1 CCNPs). The injection was consecutively given through the lateral tail vein once per day for 14 d. The body weights and daily feed intakes of the rats in various groups were measured. The haematology indexes, serum biochemical indexes, relative weights of organs and histopathology of main organs of the rats in various groups were detected. Results:In the 14-day repeated dose toxicity experiment, two rats died in high dose of CCNPs group, while no rats died in low and middle doses of CCNPs groups. The body weights and daily average intakes of the rats in different doses of CCNPs groups were slightly lower than those in control group, but the differences were not statistically significant (P>0.05). There were no significant differences in the serum indexes of the rats between different doses of CCNPs groups and control group(P>0.05). Compared with control group, the relative weights of lung of the rats in different doses of CCNPs groups were increased significant (P<0.05); the relative weights of spleen of the rats in low and middle doses of CCNPs groups were increased significantly (P<0.05); while the relative weight of spleen of the rats in high dose of CCNPs group had no significant difference(P>0.05). The histopathological analysis results showed that the mild inflammatory infiltration was found in some organs of the rats in low dose of CCNPs group, while no obviously pathological changes were found. The obviously histopathological changes were observed in the main organs of the rats in middle and high doses of CCNPs groups, including inflammatory cell infiltration, slight disorder of hepatocytes arrangement, increased vacuoles in hepatocytes; thickening of alveolar interstitium and formation of granulomas in the lung tissue; swelling, rupture and even necrosis of cardiac muscle fibers; atrophy and fissures of glomerulus and so on. Conclusion:Intravenous administration of low dose of CCNPs couldn't cause sever acute toxicity reaction.