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茴香霉素抗賈第蟲(chóng)的作用研究

發(fā)布時(shí)間:2018-01-23 09:05

  本文關(guān)鍵詞: 茴香霉素 賈第蟲(chóng) 體內(nèi) 體外 出處:《吉林大學(xué)》2017年碩士論文 論文類型:學(xué)位論文


【摘要】:十二指腸賈第鞭毛蟲(chóng)(Giardia duodenalis),簡(jiǎn)稱賈第蟲(chóng)(Giardia),曾被稱為藍(lán)氏賈第蟲(chóng)(Giardia lamblia)。賈第蟲(chóng)是一種重要的人獸共患原蟲(chóng)病病原,主要寄生在人、犬、貓、家畜動(dòng)物的腸道,可引起腹瀉、腹痛、消化不良以及體重下降。賈第蟲(chóng)在我國(guó)相當(dāng)流行,我國(guó)城市供水水質(zhì)和生活飲用水衛(wèi)生標(biāo)準(zhǔn)均把賈第蟲(chóng)檢測(cè)作為必檢指標(biāo)。目前,臨床治療賈第蟲(chóng)的藥物主要有甲硝唑、替硝唑以及阿苯噠唑等[1],均不同程度上存在副作用和耐藥性等問(wèn)題,研發(fā)治療賈第蟲(chóng)病的新藥仍是熱點(diǎn)問(wèn)題。茴香霉素是從淺灰色鏈霉菌分離的一種抗生素,對(duì)陰道毛滴蟲(chóng)、阿米巴原蟲(chóng)等具有一定的殺滅作用,但未見(jiàn)關(guān)于茴香霉素對(duì)賈第蟲(chóng)作用的報(bào)道。本研究擬通過(guò)體外試驗(yàn)和體內(nèi)試驗(yàn)觀察茴香霉素的抗賈第蟲(chóng)作用,以期為賈第蟲(chóng)新藥的研發(fā)提供理論依據(jù)和技術(shù)支持。茴香霉素體外抗賈第蟲(chóng)的作用研究本研究觀察了不同濃度茴香霉素對(duì)賈第蟲(chóng)滋養(yǎng)體生長(zhǎng)的影響,當(dāng)茴香霉素濃度為5μg/ml,賈第蟲(chóng)滋養(yǎng)體數(shù)量減少97.3%。茴香霉素的最低抑制濃度為0.0167μg/ml。利用掃描電鏡觀察了茴香霉素(0.5μg/ml)對(duì)賈第蟲(chóng)滋養(yǎng)體形態(tài),發(fā)現(xiàn)經(jīng)茴香霉素處理后,滋養(yǎng)體表面凹凸不平,表面細(xì)胞膜有一定程度的破裂,內(nèi)容物出現(xiàn)外溢。茴香霉素對(duì)賈第蟲(chóng)感染小鼠的治療作用研究通過(guò)人工感染小鼠1×105個(gè)賈第蟲(chóng)包囊,藥物治療試驗(yàn)發(fā)現(xiàn)茴香霉素濃度為10 mg/kg,小鼠體內(nèi)賈第蟲(chóng)滋養(yǎng)體數(shù)量減少30%,其平均體重超過(guò)陽(yáng)性對(duì)照組。腸道組織切片觀察發(fā)現(xiàn)藥物劑量組病理變化輕微,與陰性對(duì)照組相近。陽(yáng)性對(duì)照組出現(xiàn)腸絨毛結(jié)構(gòu)破損及炎性浸潤(rùn)。通過(guò)Elisa法檢測(cè)腸系膜淋巴結(jié)的細(xì)胞因子水平發(fā)現(xiàn),藥物組均高于陽(yáng)性對(duì)照組。茴香霉素對(duì)賈第蟲(chóng)感染犬的治療作用研究通過(guò)人工感染犬5×106個(gè)賈第蟲(chóng)包囊,進(jìn)行藥物治療發(fā)現(xiàn)茴香霉素劑量為10 mg/kg時(shí),犬體內(nèi)的賈第蟲(chóng)滋養(yǎng)體數(shù)量減少45%。茴香霉素劑量組的試驗(yàn)犬平均增重率超過(guò)賈第蟲(chóng)陽(yáng)性對(duì)照組。腸道組織切片觀察發(fā)現(xiàn)藥物劑量組病理變化輕微,與陰性對(duì)照組相近,而陽(yáng)性對(duì)照組出現(xiàn)腸絨毛結(jié)構(gòu)破損。
[Abstract]:Giardia duodenalisa (Giardia giardia). Giardia lamblia, once known as Giardia lamblia, is an important zoonotic parasite that parasitizes the intestines of humans, dogs, cats, and domestic animals. It can cause diarrhea, abdominal pain, indigestion and weight loss. Jiardia is very popular in our country. The main drugs for the treatment of giardia are metronidazole, tinidazole and albendazole. [1. There are some side effects and drug resistance in different degree. The research and development of new drug for giardiosis is still a hot issue. Anisomycin is an antibiotic isolated from Streptomyces grayrifolia, which is resistant to Trichomonas vaginalis. Amoeba protozoa has certain killing effect, but there is no report on the effect of anisomycin on giardia. This study aims to observe the anti-giardia effect of anisomycin through in vitro and in vivo experiments. In order to provide theoretical basis and technical support for the research and development of Giardia lamblia in vitro the effects of anisomycin on the growth of Giardia japonica trophozoites were studied. When anisomycin concentration was 5 渭 g / ml. The number of trophozoites of Giardia decreased by 97.3.The minimum inhibitory concentration of anisomycin was 0.0167 渭 g / ml. A scanning electron microscope was used to observe anisomycin 0.5 渭 g / ml. The morphology of trophozoites of Giardia japonica. It was found that the surface of trophozoites was uneven and the cell membrane of trophozoites was ruptured to a certain extent after anisomycin treatment. The therapeutic effect of anisomycin on the mice infected with Giardia lamblia was studied through artificial infection of 1 脳 105 giardia cyst. The drug therapy test showed that the concentration of fengiomycin was 10 mg / kg and the number of Giardia trophozoites in mice decreased by 30%. The average body weight of the drug group was higher than that of the positive control group. The structure of intestinal villi was damaged and inflammatory infiltration was found in the positive control group. The cytokine level of mesenteric lymph nodes was detected by Elisa method. The therapeutic effect of anisomycin on Giardia japonica infected dogs was studied by artificial infection of 5 脳 106 giardia cyst. It was found that the dosage of anisomycin was 10 mg/kg. The number of giardia trophozoites in dogs was decreased by 45%. The average weight gain rate of the dogs in the anisome group was higher than that in the positive control group. The pathological changes were slight in the drug dose group. It was similar to the negative control group, but the intestinal villus structure was damaged in the positive control group.
【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】:2017
【分類號(hào)】:S859.796

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