吸入上轉(zhuǎn)換納米顆粒對(duì)小鼠的體內(nèi)毒性研究
發(fā)布時(shí)間：2018-10-13 08:41
【摘要】：上轉(zhuǎn)換納米顆粒（upconversion nanoparticles，UCNPs）是由數(shù)種稀土元素?fù)诫s于某些固體晶格中構(gòu)成的納米顆粒。它能夠吸收低能級(jí)光子而發(fā)出高能級(jí)光子，是新興的最富前景的納米材料之一。 由于獨(dú)特的原子結(jié)構(gòu)，上轉(zhuǎn)換納米顆粒是由低能級(jí)長(zhǎng)波長(zhǎng)的近紅外線激發(fā)，相對(duì)于傳統(tǒng)的發(fā)光物質(zhì)，避免了短波長(zhǎng)激發(fā)光（通常是紫外線）產(chǎn)生自體熒光的干擾，且因?yàn)椴ㄩL(zhǎng)長(zhǎng)，對(duì)生物組織的穿透能力強(qiáng)而損傷小，可實(shí)現(xiàn)深部組織非侵入式探測(cè)和治療。上轉(zhuǎn)換納米顆粒具有優(yōu)越的光學(xué)特性還包括：發(fā)射光穩(wěn)定性好、無(wú)光閃爍、無(wú)光漂白，可以實(shí)現(xiàn)長(zhǎng)期激發(fā)以便觀察檢測(cè)；最大吸收峰與最大發(fā)射峰之間波長(zhǎng)差大，避免激發(fā)光對(duì)發(fā)射光檢測(cè)的干擾；激發(fā)光譜窄，檢測(cè)靈敏度高；通過(guò)摻雜不同的稀土元素產(chǎn)生不同的發(fā)射光，可實(shí)現(xiàn)多色同時(shí)檢測(cè)。目前，上轉(zhuǎn)換納米顆粒主要應(yīng)用于生物分子檢測(cè)、細(xì)胞顯像、肝細(xì)胞移植示蹤、光動(dòng)力治療等生物醫(yī)學(xué)領(lǐng)域。 然而，要實(shí)現(xiàn)在臨床醫(yī)學(xué)領(lǐng)域更廣闊的應(yīng)用，上轉(zhuǎn)換納米顆粒需要具備生物相容性好、毒性低等條件。這需要我們從生物材料安全性角度對(duì)其毒性進(jìn)行研究。然而目前關(guān)于上轉(zhuǎn)換納米顆粒的毒理學(xué)研究大多是體外毒性研究，體內(nèi)毒性研究任重而道遠(yuǎn)。本課題在整體動(dòng)物水平，采用經(jīng)氣道滴注劑量25mg/kg.bw的方式，研究上轉(zhuǎn)換納米顆粒對(duì)小鼠整體狀態(tài)及重要臟器的形態(tài)和功能的影響，得到以下 結(jié)果： 1.經(jīng)氣道滴注上轉(zhuǎn)換納米顆粒后動(dòng)物表現(xiàn)出進(jìn)食減少、活動(dòng)減少、毛色發(fā)暗體重減輕，這些現(xiàn)象在15天后得到恢復(fù)。 2.經(jīng)氣道滴注上轉(zhuǎn)換納米顆粒后動(dòng)物肺部出現(xiàn)明顯的炎癥反應(yīng)和增生表現(xiàn)，超微結(jié)構(gòu)顯示顆粒主要存在于Ⅱ型肺泡上皮細(xì)胞中，且該細(xì)胞嗜鋨性板層小體有空虛的表現(xiàn)。肺濕干重比結(jié)果顯示，，染毒后第2天肺水明顯增多；靜態(tài)肺順應(yīng)性壓力-體積曲線右移；動(dòng)脈血偏酸性，PO2降低。 3.肝臟細(xì)胞腫脹，無(wú)法分辨細(xì)胞界限，細(xì)胞核增大松散，細(xì)胞胞漿疏松，出現(xiàn)嚴(yán)重的空泡變性。這種病變?cè)诘?天最明顯，此后逐漸恢復(fù)，到第9天時(shí)肝臟形態(tài)基本恢復(fù)正常狀態(tài)。血清生化結(jié)果發(fā)現(xiàn)谷丙轉(zhuǎn)氨酶（ALT）第1天和第2天明顯升高，總膽紅素（TBIL）沒有明顯變化。 4.腎臟病理檢查未見明顯改變，血清學(xué)檢查發(fā)現(xiàn)第1天血尿素氮（BUN）升高，肌酐（CREA）和對(duì)照組相比沒有明顯異常。 5.脾臟病理可見淋巴小結(jié)面積逐漸增大，帽部朝向紅髓，邊緣區(qū)不清晰，紅髓中分布大量淋巴細(xì)胞，15天時(shí)恢復(fù)正常形態(tài)。 6.心臟病理檢查未見明顯改變。 綜上所述，可以初步認(rèn)為：25mg/kg.bw上轉(zhuǎn)換納米顆粒通過(guò)氣道單次進(jìn)入小鼠體內(nèi)后，機(jī)體有一過(guò)性的毒性反應(yīng)；其主要靶器官為肺臟和肝臟，能引起相應(yīng)器官形態(tài)和功能的損害；能引發(fā)脾臟的體液免疫反應(yīng)；引起腎小球?yàn)V過(guò)功能短暫下降；對(duì)心臟形態(tài)沒有影響。
[Abstract]:Upconversion nanoparticles (upconversion nanoparticles,UCNPs) are nanoparticles doped with several rare earth elements in some solid lattices. It can absorb low-level photons and emit high-energy photons. It is one of the most promising nanomaterials. Due to its unique atomic structure, the up-conversion nanoparticles are excited by low energy level and long wavelength near infrared ray. Compared with traditional luminescent materials, it avoids the interference of short wavelength excited light (usually UV) from autofluorescence. Because of the long wavelength and the strong penetrating ability to biological tissue, it can be used to detect and treat deep tissues in a non-invasive manner. The up-conversion nanoparticles also have excellent optical properties, such as good emission stability, no light scintillation, no light bleaching, can be excited for a long time for observation and detection, and the wavelength difference between the maximum absorption peak and the maximum emission peak is large. Avoid the interference of excitation light to emission detection; narrow excitation spectrum and high detection sensitivity; by doping different rare earth elements to produce different emission light, multi-color simultaneous detection can be realized. At present, upconversion nanoparticles are mainly used in biomedical fields such as biomolecules detection, cell imaging, hepatocyte transplantation tracer, photodynamic therapy and so on. However, in order to be more widely used in clinical medicine, up-conversion nanoparticles need good biocompatibility and low toxicity. This requires us to study the toxicity of biomaterials from the point of view of their safety. However, most of the toxicological studies on upconversion nanoparticles are in vitro toxicity studies. At the whole animal level, the effects of up-conversion nanoparticles on the whole state of mice and the morphology and function of important organs were studied by the way of transairway infusion dose of 25mg/kg.bw. The results were as follows: 1. The animals showed a decrease in food intake, decreased activity and loss of dark weight of hair color after instillation of nanoparticles through the airway. These phenomena recovered after 15 days. 2. There were obvious inflammatory reaction and proliferation in the lungs of the animals after instillation of the nanoparticles in the airway. The ultrastructure showed that the granules mainly existed in type 鈪
本文編號(hào)：2267978
[Abstract]:Upconversion nanoparticles (upconversion nanoparticles,UCNPs) are nanoparticles doped with several rare earth elements in some solid lattices. It can absorb low-level photons and emit high-energy photons. It is one of the most promising nanomaterials. Due to its unique atomic structure, the up-conversion nanoparticles are excited by low energy level and long wavelength near infrared ray. Compared with traditional luminescent materials, it avoids the interference of short wavelength excited light (usually UV) from autofluorescence. Because of the long wavelength and the strong penetrating ability to biological tissue, it can be used to detect and treat deep tissues in a non-invasive manner. The up-conversion nanoparticles also have excellent optical properties, such as good emission stability, no light scintillation, no light bleaching, can be excited for a long time for observation and detection, and the wavelength difference between the maximum absorption peak and the maximum emission peak is large. Avoid the interference of excitation light to emission detection; narrow excitation spectrum and high detection sensitivity; by doping different rare earth elements to produce different emission light, multi-color simultaneous detection can be realized. At present, upconversion nanoparticles are mainly used in biomedical fields such as biomolecules detection, cell imaging, hepatocyte transplantation tracer, photodynamic therapy and so on. However, in order to be more widely used in clinical medicine, up-conversion nanoparticles need good biocompatibility and low toxicity. This requires us to study the toxicity of biomaterials from the point of view of their safety. However, most of the toxicological studies on upconversion nanoparticles are in vitro toxicity studies. At the whole animal level, the effects of up-conversion nanoparticles on the whole state of mice and the morphology and function of important organs were studied by the way of transairway infusion dose of 25mg/kg.bw. The results were as follows: 1. The animals showed a decrease in food intake, decreased activity and loss of dark weight of hair color after instillation of nanoparticles through the airway. These phenomena recovered after 15 days. 2. There were obvious inflammatory reaction and proliferation in the lungs of the animals after instillation of the nanoparticles in the airway. The ultrastructure showed that the granules mainly existed in type 鈪
本文編號(hào)：2267978
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