本文選題：萘酚喹　切入點(diǎn)：抗瘧藥　出處：《大理學(xué)院》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：瘧疾嚴(yán)重危害著人類的生命健康,世界衛(wèi)生組織(The world health organization,簡(jiǎn)稱WHO)把它被列為全球三大公共衛(wèi)生問(wèn)題之一。瘧疾的病原體是瘧原蟲,屬于蟲媒傳染病,其發(fā)病率、死亡率在世界上最高,是地球上流行范圍最廣、危害程度最大的寄生蟲病,主要在東南亞、中南美洲及非洲等熱帶國(guó)家流行,其中非洲國(guó)家最嚴(yán)重,集中在撒哈拉沙漠以南的大部分國(guó)家。2010年WHO發(fā)表的世界瘧疾報(bào)告顯示,目前瘧疾在108個(gè)國(guó)家和地區(qū)流行,大約33億人受到威脅,每年近似2億病例,大約80萬(wàn)人死亡,絕大部分是五歲以下的兒童。 在我國(guó),瘧疾也危害著人民的身體健康與生命安全。瘧疾曾經(jīng)在我國(guó)80%的縣市流行,居傳染病之首。瘧疾的防治工作自建國(guó)以來(lái)取得了很大的成績(jī),并且在全國(guó)建立了檢測(cè)機(jī)構(gòu)和防治機(jī)構(gòu),開展了許多有效的瘧疾防治工作,取得了很大的成績(jī),發(fā)病率大幅度的降低。 萘酚喹是我國(guó)研發(fā)的新型4-氨基喹啉類抗瘧藥,對(duì)各種瘧原蟲紅內(nèi)期無(wú)性體有殺滅作用,具有治愈率高,殺蟲徹底、復(fù)燃率低等特點(diǎn),同時(shí)具有較長(zhǎng)半衰期,可以作為一個(gè)很好的治療或預(yù)防藥物。但缺點(diǎn)是起效慢。為了發(fā)掘和合理地應(yīng)用萘酚喹,有必要對(duì)其衍生物做一研究。 研究目的： 1建立伯氏瘧原蟲K173株鼠瘧模型,對(duì)常用抗瘧藥氯喹、青蒿素和萘酚喹進(jìn)行測(cè)試,證明鼠瘧模型對(duì)它們敏感。說(shuō)明此模型可用于新化合物的評(píng)價(jià)。 2用鼠瘧模型對(duì)抗瘧藥萘酚喹衍生物的藥效進(jìn)行評(píng)價(jià)。 3培養(yǎng)研究生的科研能力和科研思維。 4學(xué)會(huì)處理實(shí)驗(yàn)過(guò)程中遇到問(wèn)題的解決能力。 研究方法： Peters4天抑制試驗(yàn)法。采供血鼠的尾巴血,然后按照所需的比例進(jìn)行稀釋,接種到實(shí)驗(yàn)鼠體內(nèi)(含1×107個(gè)感染紅細(xì)胞)。腹腔注射0.2ml藥物,連續(xù)4天給藥,依次為D0,D1,D2,D3,第5天處理結(jié)果。給藥物分多個(gè)濃度,每個(gè)濃度和空白各5只小鼠。2h以后灌胃給藥,連給4天,第5天采尾血進(jìn)行涂片,甲醇固定,吉姆薩染色后油鏡下觀察3個(gè)區(qū)域各200個(gè)紅細(xì)胞以上,計(jì)算感染率。 瘧原蟲寄生率=感染的紅細(xì)胞數(shù)(IRBC)÷紅細(xì)胞總數(shù)(RBC)×100% 結(jié)果： 1昆明系小鼠對(duì)K173株較敏感,且青蒿素對(duì)伯氏瘧原蟲K173株的ED50和ED9o值分別為18.86mg/kg和54.83mg/kg,氯喹對(duì)K173株的ED50和ED90值分別為2.32mg/kg和21.88mg/kg,萘酚喹對(duì)K173株的ED50和ED90的值分別為0.42mg/kg和1.08mg/kg。圖形的擬合度高,即得出的ED50和ED90值準(zhǔn)確度高,所建鼠瘧模型可用于抗瘧藥的藥效評(píng)價(jià)。 2化合物1、2、3、5、6、7、8、9、12、13、21、23、24號(hào)萘酚喹衍生物對(duì)對(duì)K173株的抑制作用和萘酚喹相近。24個(gè)化合物中的化合物1和化合物13對(duì)伯氏瘧原蟲K173株的抑制作用最強(qiáng)；化合物1(ED50=0.40mg/kg；ED90=1.01mg/kg)和衍生物13(ED50=0.38mg/kg;ED90=0.61mg/kg)的ED50,和ED90與萘酚喹的ED50和ED90相近,圖形曲線的模擬度高,有研究的價(jià)值�；衔�4、10、11、14、15、16、17、18、19、20、22號(hào)的藥效學(xué)顯示,和萘酚喹的ED50和ED90有差別,但可以做進(jìn)一步的研究。 結(jié)論： 14天抑制實(shí)驗(yàn)法是抗瘧藥篩選的標(biāo)準(zhǔn)測(cè)試,通常也用于藥物的篩選。此次實(shí)驗(yàn)得出的數(shù)據(jù)說(shuō)明伯氏瘧原蟲K173株對(duì)傳統(tǒng)的抗瘧藥的敏感性是高的,模型是可用的�？捎糜谳练余苌锏乃幮гu(píng)價(jià)。 2伯氏瘧原蟲K173株對(duì)萘酚喹衍生物的敏感性不完全相同。軍事醫(yī)學(xué)科學(xué)院微生物流行病研究所新合成的24種萘酚喹衍生物中,有2種與萘酚喹的ED50和ED90與萘酚喹的ED50和ED90相近。具有進(jìn)一步研究的價(jià)值；有11種與萘酚喹的ED50和ED90值有差別,但可以做進(jìn)一步的調(diào)節(jié)研究。這對(duì)我們進(jìn)一步研究萘酚喹衍生物奠定了一定的基礎(chǔ)。
[Abstract]:Malaria serious harm to human life and health, WHO (The World Health Organization, referred to as WHO) it is listed as one of the world's three major public health problems. The causative agent of malaria is a parasite, belonging to insect borne infectious diseases, the incidence rate, mortality was highest in the world, the earth is the most popular, the biggest harm degree parasitic disease, mainly popular in Southeast Asia, Latin America and Africa tropical countries, including African countries most seriously, on display in the Sahara desert to the south of.2010 in most of the World Malaria Report published by WHO, popular in 108 countries and regions of the malaria, about 3 billion 300 million people are threatened, approximately 200 million cases annually, about the death of 800 thousand people, mostly children under the age of five.
In our country, malaria also do harm to people's health and safety. Malaria in China was 80% of the counties in the epidemic of infectious diseases, the first. The prevention and treatment of malaria has made great achievements since the founding of new China, and the establishment of the detection mechanism and prevention and control institutions in the country, to carry out a number of effective malaria prevention and control work that has made great achievements, the incidence rate decreased greatly.
Naphthoquine is China's developed a new type of 4- aminoquinolines antimalarial drugs, killing effect on various Plasmodium asexual erythrocytic stages, with high cure rate, low recurrence rate of insecticide thoroughly, at the same time, has a longer half-life, can serve as a good therapeutic or preventive drugs. But the disadvantage is slow. In order to explore and rational application of naphthoquine, it is necessary to do a research on its derivatives.
The purpose of the study is:
1, we established the rat malaria model of K173 strain of Plasmodium bergi, and tested the commonly used antimalarial drugs, such as chloroquine, artemisinin and naphthoquine, which showed that the rat malaria model is sensitive to them. This model can be used for the evaluation of new compounds.
2 the efficacy of the antimalarial model was evaluated against the efficacy of the naphthol quinoline derivatives.
3 training graduate students' scientific research ability and scientific research thinking.
4 learn how to deal with problems in the process of the experiment.
Research methods:
Peters4 inhibition test. Blood rat tail blood was diluted and then according to the required proportion, were inoculated into mice (containing 1 x 107 infected red blood cells). The intraperitoneal injection of 0.2ml drugs, administered for 4 consecutive days, followed by D0, D1, D2, D3, fifth days of treatment results. For multiple drug concentration, concentration of each blank and 5 mice of each.2h after intragastric administration for 4 days, even fifth days, blood samples were smeared, fixed with methanol, after Giemsa staining under microscope observation of the above 3 areas of the 200 red blood cells, calculate the infection rate.
Plasmodium parasitism rate = infected red blood cells (IRBC), red blood cell count (RBC) * 100%
Result錛，

本文編號(hào)：1568666