本文選題：鉛 + 高脂飲食　； 參考：《華北理工大學(xué)》2017年碩士論文

【摘要】：目的本研究從脈絡(luò)叢調(diào)控免疫細(xì)胞進(jìn)入中樞神經(jīng)系統(tǒng)的角度探討在鉛和高脂飲食條件下中樞神經(jīng)系統(tǒng)炎性微環(huán)境的變化的機(jī)制,以期為鉛和高脂飲食暴露致神經(jīng)損傷的生物標(biāo)志物的研究提供新的靶點(diǎn)。方法1實(shí)驗(yàn)動(dòng)物處理及分組:60只健康C57BL/6J雄性小鼠,隨機(jī)分為對(duì)照組,高脂飲食組,鉛暴露組,鉛暴露+高脂飲食組。采用自由飲水的方式染毒,染毒時(shí)間為12周。對(duì)照組予基礎(chǔ)飼料喂養(yǎng),高脂飲食組予高脂飼料喂養(yǎng),鉛暴露組予基礎(chǔ)飼料喂養(yǎng)同時(shí)飲用質(zhì)量濃度為300mg/L的醋酸鉛飲用水;鉛暴露+高脂飲食組予飲用質(zhì)量濃度為300 mg/L的醋酸鉛飲用水同時(shí)予高脂飼料喂養(yǎng)。2應(yīng)用Morris水迷宮、新物體識(shí)別實(shí)驗(yàn)及曠場(chǎng)試驗(yàn)對(duì)小鼠進(jìn)行神經(jīng)行為測(cè)試。3應(yīng)用ICP-MS法檢測(cè)小鼠海馬組織中鉛元素的含量。4應(yīng)用ELISA法和試劑盒檢測(cè)小鼠血清中總膽固醇(T-CHO)、甘油三酯(TG)的含量和海馬中炎癥因子及BDNF含量的變化。5應(yīng)用流式細(xì)胞術(shù)檢測(cè)血液、脾臟中Th1/CD4+、Th2/CD4+、Th17/CD4+百分率的變化。6應(yīng)用real-time PCR檢測(cè)小鼠脈絡(luò)叢中粘連蛋白VCAM-1、ICAM-1的m RNA表達(dá)的變化。計(jì)量資料的統(tǒng)計(jì)學(xué)描述以-x±s表示,不同組別間比較應(yīng)用方差分析和兩兩比較的LSD檢驗(yàn),P0.05具有統(tǒng)計(jì)學(xué)意義。結(jié)果1.實(shí)驗(yàn)小鼠生長(zhǎng)發(fā)育情況:各組小鼠體重隨時(shí)間延長(zhǎng)均升高,給予高脂飲食小鼠體重顯著高于普通飼料喂養(yǎng)小鼠(P0.05)。2.鉛和高脂飲食暴露對(duì)小鼠血清中總膽固醇(T-CHO)、甘油三酯(TG)的影響:高脂飲食小鼠血液中總膽固醇(T-CHO)、甘油三酯(TG)含量升高(P0.05);未見(jiàn)鉛暴露+高脂飲食組小鼠血清中T-CHO、TG含量較高脂飲食組有明顯變化。3.鉛和高脂飲食暴露對(duì)小鼠神經(jīng)行為功能的影響:高脂飲食組、鉛暴露組、鉛暴露+高脂飲食組小鼠的潛伏期高于對(duì)照組,穿臺(tái)次數(shù)下降(P0.05)。與高脂飲食組及鉛暴露組相比,鉛暴露+高脂飲食組第3天潛伏期明顯延長(zhǎng),穿臺(tái)次數(shù)減少(P0.05)。與對(duì)照組比較,高脂飲食組、鉛暴露組、鉛暴露+高脂飲食組小鼠中央?yún)^(qū)域路程及站立次數(shù)均減少(P0.05);鉛暴露+高脂飲食組小鼠中央?yún)^(qū)域路程較高脂飲食組或鉛暴露組明顯下降,差異有統(tǒng)計(jì)學(xué)意義(P0.05)4.鉛和高脂飲食暴露對(duì)小鼠海馬組織中鉛含量的影響:鉛暴露組、鉛暴露+高脂飲食組小鼠海馬中的鉛含量分別為對(duì)照組的8.8倍、9.6倍;與高脂飲食組相比,鉛暴露組、鉛暴露+高脂飲食組小鼠海馬中的鉛含量均增加(P0.05)。5.鉛和高脂飲食暴露對(duì)海馬中炎癥因子及BDNF的影響:高脂飲食或鉛暴露小鼠海馬中炎癥因子IL-17、IL-6、IL-1b、IFN-g水平高于對(duì)照組,鉛暴露和高脂飲食聯(lián)合暴露小鼠海馬中IL-17、IL-1b的水平高于單獨(dú)暴露組(P0.05)。與對(duì)照組相比,高脂飲食組、鉛暴露組BDNF含量均下降;未見(jiàn)鉛暴露+高脂飲食組海馬中BDNF含量較高脂飲食組或鉛暴露組有明顯差異。6.鉛和高脂飲食暴露對(duì)小鼠血清中炎癥因子的影響:與對(duì)照組比較,高脂飲食組、鉛暴露組、鉛暴露+高脂飲食組血清中IL-17含量增加,TGF-β1含量下降(P0.05)。鉛暴露+高脂飲食組血清中IL-17含量較高脂飲食組或鉛暴露組明顯升高(P0.05)。7.鉛和高脂飲食暴露對(duì)小鼠血液、脾臟中Th1/CD4+、Th2/CD4+、Th17/CD4+百分率的影響:高脂飲食組、鉛暴露組、鉛暴露+高脂飲食組血液中Th1/CD4+的百分率分別為2.10%、3.48%、4.18%,高于對(duì)照組的1.74%。Th17/CD4+的百分率分別為1.42%、1.46%、1.56%;高于對(duì)照組的0.67%。高脂飲食組、鉛暴露組、鉛暴露+高脂飲食組脾臟中Th1/CD4+的百分率分別為11.16%、13.23%、12.11%,較對(duì)照組的6.90%明顯升高。Th17/CD4+的百分率分別為3.58%、3.78%、4.18%,高于對(duì)照組的2.62%;鉛暴露+高脂飲食組血液、脾臟中Th2/CD4+的百分率顯著降低(P0.05)。分別與高脂飲食組和鉛暴露相比較,鉛暴露+高脂飲食組血液中Th1/CD4+的百分率升高,血液及脾臟中Th2/CD4+的百分率降低(P0.05)。8.鉛和高脂飲食暴露對(duì)小鼠脈絡(luò)叢中粘連蛋白VCAM-1、ICAM-1 m RNA表達(dá)影響:對(duì)照組比較,鉛暴露、高脂飲食可導(dǎo)致小鼠脈絡(luò)叢中VCAM-1、ICAM-1的m RNA表達(dá)增加(P0.05);與高脂飲食組和鉛暴露組相比,鉛暴露+高脂飲食組VCAM-1的m RNA表達(dá)均顯著上調(diào)(P0.05)。結(jié)論鉛暴露和高脂飲食均可導(dǎo)致小鼠認(rèn)知功能所傷,學(xué)習(xí)記憶能力和探究能力下降,且鉛與高脂飲食聯(lián)合暴露可加劇神經(jīng)損傷,這可能與外周血中的免疫細(xì)胞及脈絡(luò)叢的免疫監(jiān)視功能失調(diào),引起中樞神經(jīng)系統(tǒng)炎性微環(huán)境的改變有關(guān)。
[Abstract]:Objective to explore the mechanism of the changes in the inflammatory microenvironment of the central nervous system under the lead and high fat diet, in order to provide new targets for the study of biomarkers in lead and high fat diet exposure, in order to provide a new target for the study of biomarkers in lead and high fat diet exposure. Methods 1 experimental animals were treated and divided into groups: 60 Only healthy C57BL/6J male mice were randomly divided into control group, high fat diet group, lead exposure group, lead exposure + high fat diet group. The free drinking water was used for 12 weeks. The control group was fed with basic diet, high fat diet group was fed with high fat diet, and the lead exposure group was given the quality of basic diet for 300mg/L. Lead acetate drinking water; lead exposure + high fat diet group give drinking water with a drinking mass of 300 mg/L of lead acetate drinking water and high fat diet feeding.2 Morris water maze; new object identification experiment and open field test on mice neurobehavioral test.3 application ICP-MS method to detect the content of lead in hippocampus of mice.4 application ELISA method The changes of total cholesterol (T-CHO), triglyceride (TG), inflammatory factors and BDNF content in the hippocampus were detected by the kit and kits..5 applied flow cytometry to detect the blood and the changes of Th1/CD4+, Th2/CD4+, Th17/CD4+ percentage in the spleen. Real-time PCR was used to detect the VCAM-1 of the adhesion protein in the choroid series of mice. The statistical description of the measurement data was expressed as -x + s, and the variance analysis and the 22 comparison LSD test were used among the different groups. The growth and development of the 1. experimental mice were increased. The weight of the mice in each group increased with time, and the weight of the mice was significantly higher than that of the normal feed mice (P 0.05) the effect of.2. lead and high fat diet exposure on serum total cholesterol (T-CHO) and triglyceride (TG) in mice: high fat diet mice blood total cholesterol (T-CHO), triglyceride (TG) content increased (P0.05); no lead exposure + high fat diet group of mice serum T-CHO, TG content high fat diet group has obvious changes of.3. lead and high fat diet exposure The effects on the neurobehavioral function of mice: high fat diet group, lead exposure group, lead exposure + high fat diet group were higher than the control group, the number of wear stage decreased (P0.05). Compared with the high fat diet group and lead exposure group, the third day latency of lead exposure + high fat diet group was obviously prolonged and the number of table wearing decreased (P0.05). In the diet group, lead exposure group, lead exposure + high fat diet group, the central area and the number of standing were decreased (P0.05); lead exposure + high fat diet group had a significant decrease in the central area of the central region of the high fat diet group or lead exposure group. The difference was statistically significant (P0.05) the effect of lead and high fat diet exposure on the lead content in the hippocampus of mice: Lead Lead exposure in the hippocampus of exposure group, lead exposure + high fat diet group was 8.8 times and 9.6 times as high as that of the control group. Lead exposure group, lead exposure group, lead exposure + high fat diet group increased the lead content in hippocampus of mice (P0.05).5. lead and high fat diet exposure on the hippocampus inflammatory factors and BDNF: high fat diet or lead exposure small exposure The levels of inflammatory factors IL-17, IL-6, IL-1b, and IFN-g in the hippocampus of rats were higher than those in the control group. The level of IL-17 and IL-1b in the hippocampus of mice exposed to lead exposure and high fat diet was higher than that of the single exposure group (P0.05). Compared with the control group, the levels of BDNF in the lead exposed group and the high fat diet group were lower than those in the control group, and there was no higher BDNF content in the hippocampus of the lead exposed and high fat diet group. The effects of.6. lead exposure and high fat diet exposure on the serum inflammatory factors in mice were significantly different. Compared with the control group, the content of IL-17 in the serum of high fat diet group, lead exposure group, lead exposure + high fat diet group increased, TGF- beta 1 decreased (P0.05). The IL-17 content in the serum of lead exposure + high fat diet group was higher than that of fat diet group or lead group The exposure group significantly increased the percentage of Th1/CD4+, Th2/CD4+ and Th17/CD4+ in the blood and spleen of mice (P0.05).7. lead and high fat diet exposure: the percentage of Th1/CD4+ in the blood of high fat diet group, lead exposure group, lead exposure + high fat diet group was 2.10%, 3.48%, 4.18% respectively, and the percentage of 1.74%.Th17/CD4+ in the control group was 1.42%, 1.4 respectively. 6%, 1.56%; the percentage of Th1/CD4+ in the 0.67%. high fat diet group, lead exposure group, lead exposure + high fat diet group was 11.16%, 13.23%, 12.11% respectively, compared with the control group, the percentage of.Th17/CD4+ was 3.58%, 3.78%, 4.18%, higher than the control group 2.62%, lead exposure + high fat diet group blood, Th2/CD4 in spleen. The percentage of + is significantly lower (P0.05). Compared with the high fat diet group and the lead storm, the percentage of Th1/CD4+ in the blood and the spleen in the high fat diet group increased, the percentage of Th2/CD4+ in the blood and spleen decreased (P0.05).8. lead and high fat diet exposure on the VCAM-1 and ICAM-1 m RNA expression in the choroid series of mice: comparison group, Lead exposure, high fat diet can lead to VCAM-1 and ICAM-1 m RNA expression in mouse choroid clusters (P0.05). Compared with high fat diet group and lead exposure group, the m RNA expression of VCAM-1 in lead exposure + high fat diet group is significantly up (P0.05). Conclusion lead exposure and high fat diet can lead to cognitive impairment, learning and memory ability and exploration ability in mice. Decrease, and combined exposure of lead and high fat diet can aggravate nerve damage, which may be associated with the immune monitoring of the immune cells and choroid plexus in peripheral blood, which may cause changes in the inflammatory microenvironment of the central nervous system.

【學(xué)位授予單位】：華北理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114

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