口服暴露碳納米管對(duì)小鼠胃腸道的影響
發(fā)布時(shí)間：2018-09-02 07:48
【摘要】：碳納米管（Carbon nanotubes, CNTs）具有超高的機(jī)械強(qiáng)度和彈性、優(yōu)良的導(dǎo)體和半導(dǎo)體特性等獨(dú)特的物理化學(xué)性質(zhì)，在電子、光學(xué)、儲(chǔ)能、催化、復(fù)合材料以及生物醫(yī)藥等諸多領(lǐng)域已有廣泛的應(yīng)用并具有廣闊的應(yīng)用前景。碳納米管是目前納米醫(yī)學(xué)領(lǐng)域的一個(gè)新興的方向和研究熱點(diǎn)，例如可以用于生物探針、藥物載體、腫瘤治療、生物支架及生物傳感器等。另外，在食品生產(chǎn)方面，也可以用做食品添加劑以及食品包裝材料。伴隨著CNTs的大規(guī)模生產(chǎn)以及愈來(lái)愈多的日常生活、生物醫(yī)學(xué)等領(lǐng)域的廣泛應(yīng)用，其生物安全性問(wèn)題也日益引起人們的嚴(yán)重關(guān)注。 納米材料可以通過(guò)皮膚系統(tǒng)、呼吸系統(tǒng)、醫(yī)療注射、消化系統(tǒng)等途徑進(jìn)入到人體。諸如，分散在空氣中的納米顆粒通過(guò)呼吸進(jìn)入人體，成為最常的途徑之一。納米顆粒通過(guò)呼吸作用，進(jìn)入鼻咽部、氣管（支氣管）、肺泡，之后借助纖毛運(yùn)動(dòng)，經(jīng)口腔可以進(jìn)入胃腸道；又如，納米材料也可經(jīng)過(guò)皮膚接觸運(yùn)達(dá)全身；另外，食品和藥物中的納米材料、納米添加劑亦可通過(guò)口服，伴隨著食物藥物一同進(jìn)入胃腸道。而胃腸道作為人體最主要的消化吸收器官，在抵御外源物質(zhì)和病原菌入侵方面具有重要的作用。 研究碳納米管對(duì)人體及動(dòng)物胃腸道系統(tǒng)的生物效應(yīng)及安全性具有重要的意義。一是因?yàn)槿藗兘佑|碳納米管的機(jī)會(huì)增多；二是因?yàn)樘技{米管通過(guò)多種途徑進(jìn)入人體后，均可以轉(zhuǎn)移到達(dá)胃腸道；三是因?yàn)槲改c道在機(jī)體內(nèi)的重要功能作用，起到消化吸收、免疫屏障的作用。因此，本試驗(yàn)研究碳納米管對(duì)小鼠胃腸道的影響。 碳納米管按照組成的石墨片層數(shù)的不同可分為單壁碳納米管（Single-wallcarbon nanotubes, SWCNTs）和多壁碳納米管（Multi-wall carbon nanotubes,MWCNTs）。目前在生物醫(yī)療方面的應(yīng)用使用更多的是SWCNTs，所以本實(shí)驗(yàn)研究選用SWCNTs。 本實(shí)驗(yàn)主要包括兩部分，一部分是對(duì)所選用的SWCNTs進(jìn)行物理化學(xué)結(jié)構(gòu)表征，采用經(jīng)典的材料表征手段，主要有掃描電鏡、透射電鏡、拉曼光譜、X射線能譜、顆粒水合粒徑和Zate電位的測(cè)量，以便測(cè)定SWCNTs的表觀形貌、平均粒徑、團(tuán)聚狀態(tài)、雜質(zhì)種類及含量等。第二部分是研究SWCNTs對(duì)小鼠胃腸道的影響，采用口服暴露途徑，選用對(duì)SWCNTs較為敏感的ICR雄性小鼠，觀察記錄小鼠體重、飲食飲水量、皮毛和活動(dòng)狀態(tài)，分析暴露后血清生化、血常規(guī)和結(jié)腸組織病理學(xué)變化，采用PCR半定量方法測(cè)定結(jié)腸內(nèi)五類有代表性的菌種的細(xì)菌量相對(duì)變化。探討口服暴露SWCNTs對(duì)小鼠生物效應(yīng)作用、炎癥反應(yīng)以及結(jié)腸、肝臟的毒性作用，并且研究了SWCNTs對(duì)結(jié)腸內(nèi)五類有代表性的菌種的影響，分析菌群平衡與機(jī)體病生理狀態(tài)的相關(guān)性。 本研究采用體重22±2g ICR雄性小鼠通過(guò)連續(xù)7天口服灌胃SWCNTs（長(zhǎng)度1-5m，直徑1.04-1.07nm，純度90%）（暴露濃度分別為50g/天/只、500g/天/只、1000g/天/只），空白組口服灌胃0.9%NaCl水溶液，陽(yáng)性對(duì)照組口服灌胃鹽酸林可霉素溶液。在連續(xù)暴露7天后，分析小鼠的體重、血清生化、血常規(guī)和結(jié)腸組織病理學(xué)變化，定量小鼠結(jié)腸五種細(xì)菌含量變化。結(jié)果顯示，經(jīng)過(guò)7天連續(xù)口服灌胃暴露后，小鼠體重均未出現(xiàn)顯著差異。SWCNTs口服灌胃暴露后，白蛋白（ALB）和總蛋白（TP）含量均出現(xiàn)輕微下降。高劑量組小鼠在暴露下，天門冬氨酸氨基轉(zhuǎn)移酶（AST）和丙氨酸氨基轉(zhuǎn)移酶（ALT）含量均出現(xiàn)顯著地升高；而在血常規(guī)指標(biāo)中，高劑量組小鼠白細(xì)胞和淋巴細(xì)胞水平均顯著性的升高。通過(guò)HE染色觀察發(fā)現(xiàn)：SWCNTs口服灌胃暴露下，小鼠結(jié)腸組織的微絨毛結(jié)構(gòu)由于大量的炎性細(xì)胞浸潤(rùn)形成微絨毛結(jié)構(gòu)的損傷，且這種損傷作用隨著劑量的增加而更加嚴(yán)重。與對(duì)照組相比，各實(shí)驗(yàn)組小鼠的胃、結(jié)腸內(nèi)排泄物滯留較多。結(jié)腸部四種細(xì)菌含量也與對(duì)照組存在差異。 經(jīng)過(guò)連續(xù)7天口服灌胃SWCNTs暴露于小鼠后，未引起其體重的變化。在高劑量暴露下，AST和ALT含量增加，ALB和TP含量略有下降，提示小鼠可能出現(xiàn)肝功能損傷，，同時(shí)能夠顯著地引起小鼠結(jié)腸組織病理?yè)p傷。結(jié)腸部細(xì)菌含量發(fā)生變化，排泄物滯留較多，說(shuō)明SWCNTs可能通過(guò)影響菌群平衡而干擾胃腸道功能，進(jìn)而影響機(jī)體狀態(tài)。 本實(shí)驗(yàn)研究為進(jìn)一步探討SWCNTs引起體內(nèi)炎癥發(fā)生、發(fā)展的機(jī)制提供了新的可能。即SWCNTs可能通過(guò)影響菌群平衡而干擾胃腸道功能，進(jìn)而影響機(jī)體狀態(tài)，這一作用機(jī)制為深入開(kāi)展其對(duì)胃腸道的影響等研究提供了一定基礎(chǔ)和參考啟示。
[Abstract]:Carbon nanotubes (CNTs) have unique physical and chemical properties, such as ultra-high mechanical strength and elasticity, excellent conductor and semiconductor properties. They have been widely used in many fields, such as electronics, optics, energy storage, catalysis, composite materials, biomedicine and so on. At present, carbon nanotubes have broad application prospects in nanomedicine. In addition, it can also be used as food additives and food packaging materials in food production. Along with the large-scale production of CNTs and more and more daily life, biomedicine. The wide application of other fields has attracted more and more attention to its biosafety.
Nanoparticles enter the body through the skin system, respiratory system, medical injection, digestive system and other channels. For example, nanoparticles dispersed in the air enter the body through respiration, which is one of the most common ways. Nanoparticles enter the nasopharynx, trachea (bronchi), alveoli, and then through the mouth through cilia movement. It can enter the gastrointestinal tract; for example, nano-materials can also reach the whole body through skin contact; in addition, food and drug nano-materials, Nano-Additives can also be taken orally, accompanied by food and drug into the gastrointestinal tract. Masks play an important role.
It is of great significance to study the biological effects and safety of carbon nanotubes on human and animal gastrointestinal system.One reason is that people have more chances to contact carbon nanotubes.The other reason is that carbon nanotubes can be transferred to the gastrointestinal tract after entering the human body through various ways.The third reason is that the gastrointestinal tract plays an important role in the body. In this study, the effects of carbon nanotubes on gastrointestinal tract in mice were studied.
Carbon nanotubes (CNTs) can be divided into single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) according to the different layers of graphite. At present, SWCNTs are widely used in biomedical applications, so SWCNTs are selected in this study.
This experiment mainly includes two parts. One part is to characterize the physical and chemical structure of SWCNTs. The classical material characterization methods are used, such as scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray energy spectrum, particle hydration size and Zate potential measurement, in order to determine the appearance of SWCNTs, average particle size, agglomeration state, impurities. The second part is to study the effects of SWCNTs on gastrointestinal tract in mice. ICR male mice sensitive to SWCNTs were selected by oral exposure. The weight, water intake, fur and activity of mice were observed and recorded. The serum biochemistry, blood routine and histopathological changes of colon were analyzed after exposure. PCR semi-quantitative prescription was used. The relative changes of bacterial quantity of five representative bacteria in colon were determined.The biological effects, inflammation and toxicity of SWCNTs to colon and liver in mice were investigated.The effects of SWCNTs on five representative bacteria in colon were also studied.
SWCNTs (length 1-5m, diameter 1.04-1.07 nm, purity 90%) were orally administered to male ICR mice weighing 22.2 g for 7 consecutive days (exposure concentrations were 50g/day, 500g/day, 1000g/day). The blank group was orally administered 0.9% NaCl solution and the positive control group was orally administered lincomycin hydrochloride solution. Body weight, serum biochemistry, blood routine and histopathological changes of colon in mice were measured. The results showed that there was no significant difference in body weight after 7 days of continuous oral administration. After oral administration of SWCNTs, the contents of albumin (ALB) and total protein (TP) decreased slightly. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased in mice exposed to SWCNTs, while the levels of leukocytes and lymphocytes were significantly increased in mice exposed to high dose of SWCNTs. Compared with the control group, the gastric and colon excreta of the mice in each experimental group remained more. The contents of four bacteria in the colon were also different from those in the control group.
After oral administration of SWCNTs for 7 days, the body weight of the mice did not change. Under high dose exposure, the contents of AST and ALT increased, while the contents of ALB and TP decreased slightly, suggesting that the mice might suffer from liver function damage and could cause pathological damage of colon tissue. The bacterial content in colon changed and the excreta remained. More, indicating that SWCNTs may interfere with the gastrointestinal function by affecting the balance of bacteria, thereby affecting the state of the organism.
This study provides a new possibility for further exploring the mechanism of SWCNTs-induced inflammation in vivo, that is, SWCNTs may interfere with gastrointestinal function by influencing the balance of bacteria, and then affect the state of the body. This mechanism provides a certain basis and reference for further research on the effects of SWCNTs on gastrointestinal tract.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R969.1
本文編號(hào)：2218724
[Abstract]:Carbon nanotubes (CNTs) have unique physical and chemical properties, such as ultra-high mechanical strength and elasticity, excellent conductor and semiconductor properties. They have been widely used in many fields, such as electronics, optics, energy storage, catalysis, composite materials, biomedicine and so on. At present, carbon nanotubes have broad application prospects in nanomedicine. In addition, it can also be used as food additives and food packaging materials in food production. Along with the large-scale production of CNTs and more and more daily life, biomedicine. The wide application of other fields has attracted more and more attention to its biosafety.
Nanoparticles enter the body through the skin system, respiratory system, medical injection, digestive system and other channels. For example, nanoparticles dispersed in the air enter the body through respiration, which is one of the most common ways. Nanoparticles enter the nasopharynx, trachea (bronchi), alveoli, and then through the mouth through cilia movement. It can enter the gastrointestinal tract; for example, nano-materials can also reach the whole body through skin contact; in addition, food and drug nano-materials, Nano-Additives can also be taken orally, accompanied by food and drug into the gastrointestinal tract. Masks play an important role.
It is of great significance to study the biological effects and safety of carbon nanotubes on human and animal gastrointestinal system.One reason is that people have more chances to contact carbon nanotubes.The other reason is that carbon nanotubes can be transferred to the gastrointestinal tract after entering the human body through various ways.The third reason is that the gastrointestinal tract plays an important role in the body. In this study, the effects of carbon nanotubes on gastrointestinal tract in mice were studied.
Carbon nanotubes (CNTs) can be divided into single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) according to the different layers of graphite. At present, SWCNTs are widely used in biomedical applications, so SWCNTs are selected in this study.
This experiment mainly includes two parts. One part is to characterize the physical and chemical structure of SWCNTs. The classical material characterization methods are used, such as scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, X-ray energy spectrum, particle hydration size and Zate potential measurement, in order to determine the appearance of SWCNTs, average particle size, agglomeration state, impurities. The second part is to study the effects of SWCNTs on gastrointestinal tract in mice. ICR male mice sensitive to SWCNTs were selected by oral exposure. The weight, water intake, fur and activity of mice were observed and recorded. The serum biochemistry, blood routine and histopathological changes of colon were analyzed after exposure. PCR semi-quantitative prescription was used. The relative changes of bacterial quantity of five representative bacteria in colon were determined.The biological effects, inflammation and toxicity of SWCNTs to colon and liver in mice were investigated.The effects of SWCNTs on five representative bacteria in colon were also studied.
SWCNTs (length 1-5m, diameter 1.04-1.07 nm, purity 90%) were orally administered to male ICR mice weighing 22.2 g for 7 consecutive days (exposure concentrations were 50g/day, 500g/day, 1000g/day). The blank group was orally administered 0.9% NaCl solution and the positive control group was orally administered lincomycin hydrochloride solution. Body weight, serum biochemistry, blood routine and histopathological changes of colon in mice were measured. The results showed that there was no significant difference in body weight after 7 days of continuous oral administration. After oral administration of SWCNTs, the contents of albumin (ALB) and total protein (TP) decreased slightly. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased in mice exposed to SWCNTs, while the levels of leukocytes and lymphocytes were significantly increased in mice exposed to high dose of SWCNTs. Compared with the control group, the gastric and colon excreta of the mice in each experimental group remained more. The contents of four bacteria in the colon were also different from those in the control group.
After oral administration of SWCNTs for 7 days, the body weight of the mice did not change. Under high dose exposure, the contents of AST and ALT increased, while the contents of ALB and TP decreased slightly, suggesting that the mice might suffer from liver function damage and could cause pathological damage of colon tissue. The bacterial content in colon changed and the excreta remained. More, indicating that SWCNTs may interfere with the gastrointestinal function by affecting the balance of bacteria, thereby affecting the state of the organism.
This study provides a new possibility for further exploring the mechanism of SWCNTs-induced inflammation in vivo, that is, SWCNTs may interfere with gastrointestinal function by influencing the balance of bacteria, and then affect the state of the body. This mechanism provides a certain basis and reference for further research on the effects of SWCNTs on gastrointestinal tract.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R969.1
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