海扇壳源性碳酸钙纳米微粒的急性毒性作用研究
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摘要
目的:观察海扇壳源性碳酸钙纳米微粒(CCNPs)对雌性SD大鼠的急性毒性作用,初步探讨CCNPs的安全剂量。方法:健康雌性SD大鼠随机分为四组,对照组,CCNPs低、中、高剂量组,CCNPs各剂量组大鼠分别给予不同剂量(30、60、120mg/kg/d)CCNPs尾静脉注射,连续14d;对照组大鼠给予生理盐水尾静脉注射,连续14d。记录各组大鼠的生存率、毒性反应和体重的变化,HE染色观察大鼠主要脏器的病理变化。结果:实验结束时,低剂量组大鼠生存率为100.00%,中、高剂量组大鼠生存率分别为66.67%(4/6)和50.00%(3/6);CCNPs低、中剂量组大鼠体重与对照组比较差异无统计学意义(P>0.05),CCNPs高剂量组大鼠的体重明显低于对照组(P<0.05)。组织病理学观察显示,低剂量组大鼠肝脏、脾、肺、心脏和肾脏的病理变化较轻或未观察到明显病理变化,而中、高剂量组大鼠各脏器的病理变化明显较重。结论:低剂量CCNPs连续14天静脉给药不会引起雌性SD大鼠严重的急性毒性反应,CCNPs的安全剂量为≤30mg/kg。
Objective: To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles(CCNPs) on female SD rats, and to preliminarily explore the safe dose of CCNPs. Methods: Healthy female SD rats were randomly divided into 4 groups: control group, CCNPs low dose group(30 mg/kg/d), CCNPs middle dose group(60 mg/kg/d) and CCNPs high dose group(120 mg/kg/d). The rats in 3 CCNPs groups were given different dose of CCNPs by tail vein injection for 14 days continuously;The rats in control group were given normal saline by tail vein for 14 days.The survival rate, toxic effects, weight changes of rats were recorded; HE stain was used to observe the pathological changes of main organs. Results: At the end of the experiment, the survival rate of rats was respectively 100%, 66.67%(4/6) and 50.00%(3/6) in CCNPs low, middle and high dose group. There was no significant difference in body weight between CCNPs low, middle dose group and control group(P>0.05); the body weight of rats in CCNPs high dose group were obviously lower than control group(P<0.05). Histopathological observation showed that the pathological changes of liver, spleen, lung, heart and kidney in CCNPs low dose group were mild or no obvious pathological changes were observed, while the pathological changes of aboving organs in middle and high dose group were more serious. Conclusions: Intravenous administration of low dose CCNPs do not cause sever acute toxicity of female SD rats, so the safe dose of CCNPs is less than or equal to 30 mg/kg.
Objective: To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles(CCNPs) on female SD rats, and to preliminarily explore the safe dose of CCNPs. Methods: Healthy female SD rats were randomly divided into 4 groups: control group, CCNPs low dose group(30 mg/kg/d), CCNPs middle dose group(60 mg/kg/d) and CCNPs high dose group(120 mg/kg/d). The rats in 3 CCNPs groups were given different dose of CCNPs by tail vein injection for 14 days continuously;The rats in control group were given normal saline by tail vein for 14 days.The survival rate, toxic effects, weight changes of rats were recorded; HE stain was used to observe the pathological changes of main organs. Results: At the end of the experiment, the survival rate of rats was respectively 100%, 66.67%(4/6) and 50.00%(3/6) in CCNPs low, middle and high dose group. There was no significant difference in body weight between CCNPs low, middle dose group and control group(P>0.05); the body weight of rats in CCNPs high dose group were obviously lower than control group(P<0.05). Histopathological observation showed that the pathological changes of liver, spleen, lung, heart and kidney in CCNPs low dose group were mild or no obvious pathological changes were observed, while the pathological changes of aboving organs in middle and high dose group were more serious. Conclusions: Intravenous administration of low dose CCNPs do not cause sever acute toxicity of female SD rats, so the safe dose of CCNPs is less than or equal to 30 mg/kg.
引文
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[4]Fu WL,Noor MH,Yusof LM,et al.In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma[J].J Exp Nanosci,2017:1-23.
[5]Luetke A,Meyers PA,Lewis I,et al.Osteosarcoma treatment-Where do we stand?A state of the art review[J].Cancer Treat Rev,2014,40(4):523-532.
[6]Theek B,Rizzo LY,Ehling J,et al.The theranostic path to personalized nanomedicine[J].Clin Transl Imaging,2014,2(1):67-76.
[7]Lohmann DJ,Abrahamsson J,Ha SY,et al.Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia:results from NOPHO-AML 2004[J].Haematologica,2016,101(11):1359-1367.
[8]Yu T,Greish K,McGill LD,et al.Influence of geometry,porosity and surface characteristics of silica nanoparticles on acute toxicity:their vasculature effect and tolerance threshold[J].ACS Nano,2012,6(3):2289-2301.
[9]Petersen HJ,Smith AM.The role of the innate immune system in granulomatous disorders[J].Front Immunol,2013,4:120.