本文選題：青蒿琥酯 + 細粒棘球蚴��； 參考：《中國病原生物學(xué)雜志》2017年08期

【摘要】：目的了解索青蒿琥酯體外抗細粒棘球蚴氧化損傷機制。方法以二甲基亞砜(DMSO)為溶劑對照組,H2O2為活性氧(reactive oxygen species,ROS)對照組,阿苯達唑(albendazole,ABZ)和硝唑尼特(nitazoxanide,NTZ)為藥效對照組,青蒿琥酯低劑量組(65μmol/L),青蒿琥酯中劑量組(130μmol/L)和青蒿琥酯高劑量組(325μmol/L)為實驗組,采用1%伊紅染色法檢測實驗組藥物干預(yù)4d的細粒棘球蚴死亡率,并觀察病理組織學(xué)和超微結(jié)構(gòu)變化;采用雙氫羅丹明123(DHR123)法檢測細粒棘球絳蟲細粒棘球蚴體內(nèi)ROS含量動態(tài)變化;采用單細胞凝膠電泳法(彗星實驗)以O(shè)live尾距(OTM)作為DNA損傷指標(biāo)對各組細粒棘球蚴的DNA損傷情況進行分析。同時設(shè)活性氧清除劑甘露醇(mannitol,man)與藥物聯(lián)合干預(yù)細粒棘球絳蟲細粒棘球蚴試驗組作比較。結(jié)果與甘露醇聯(lián)合藥物干預(yù)組比較,青蒿琥酯中劑量組與H_2O_2組細粒棘球蚴死亡率降低(χ~2分別=46.371和59.328,P0.05);病理學(xué)觀察青蒿琥酯組細粒棘球蚴頂突小鉤脫落,角質(zhì)層、生發(fā)層結(jié)構(gòu)均遭到破壞;透射電鏡觀察細粒棘球蚴生發(fā)層出現(xiàn)大量脂滴,并且有異染色質(zhì)出現(xiàn);在330min內(nèi),青蒿琥酯低、中和高劑量組細粒棘球蚴ROS含量升高程度均明顯高于阿苯達唑組、硝唑尼特組,并具有一定的劑量依賴性;青蒿琥酯高劑量組彗星實驗圖像拖尾明顯,證明細粒棘球蚴DNA受損嚴(yán)重;青蒿琥酯低、中、高劑量組與阿苯達唑組、硝唑尼特組相比,OTM值比較均具有顯著性差異(t=9.065、13.134、7.845、9.400、12.251和7.877,P0.01)。結(jié)論青蒿琥酯抗細粒棘球蚴的作用機制可能通過產(chǎn)生ROS導(dǎo)致其DNA損傷所致,為青蒿琥酯抗包蟲病作用靶點的篩選和抗包蟲病新藥的開發(fā)奠定了基礎(chǔ)。
[Abstract]:Objective to investigate the mechanism of artesunate on oxidative injury of echinococcus granulosus in vitro. Methods dimethyl sulfoxide (DMSO) as solvent control group, H _ 2O _ 2 as active oxygen species (reactive oxygen speciesRos) control group, albendazoleoxole ABZ and nitazoxanide NTZ as control group were used as control group. Artesunate low dose group (65 渭 mol / L), middle dose group (130 渭 mol / L) and artesunate high dose group (325 渭 mol / L) were used as experimental groups. The mortality rate of Echinococcus granulosus in experimental group was detected by 1% eosinolus staining for 4 days, and histopathological and ultrastructural changes were observed. The dynamic changes of Ros content in Echinococcus granulosus were detected by dihydrorhodamine 123 (DHR123) method. Single cell gel electrophoresis (comet assay) using Olive tail distance (OTM) as DNA damage index was used to analyze DNA damage of each group of echinococcus granulosus. At the same time, the experimental group of Echinococcus granulosus (Echinococcus granulosus) treated with mannitol (mannitolman) and drugs were compared. Results compared with the mannitol combined drug intervention group, the mortality rate of artesunate in middle dose group and S _ 2O _ 2 group was lower (蠂 ~ 2 = 46.371 and 59.328 P 0.05, respectively), and artesunate group was observed by pathology to observe the exfoliation of the parietal uncinate, the keratinocyte of artesunate group, and the relation between artesunate group and S _ 2O _ 2 group (P < 0.05). The structure of germinal layer was destroyed. A large number of lipid droplets and heterochromatin were observed in the germinal layer of Echinococcus granulosus by transmission electron microscope, and artesunate was low in 330min. The Ros content of Echinococcus granulosus in middle and high dose groups was significantly higher than that in albendazole group and niazonide group in a dose-dependent manner. The results showed that DNA damage of Echinococcus granulosus was serious and the OTM values of artesunate, albendazole and niazonide groups were significantly higher than those of albendazole group and niazonide group. Conclusion the mechanism of artesunate against echinococcus granulosus may be caused by DNA damage caused by Ros, which may lay a foundation for the screening of anti-hydatid targets of artesunate and the development of new anti-hydatid drugs.
【作者單位】： 新疆醫(yī)科大學(xué)藥學(xué)院;新疆醫(yī)科大學(xué)第一附屬醫(yī)院藥學(xué)部臨床藥學(xué)科;新疆醫(yī)科大學(xué)第一附屬醫(yī)院臨床醫(yī)學(xué)研究院新疆重大疾病醫(yī)學(xué)重點實驗室-省部共建國家重點實驗室培育基地;
【基金】：國家自然科學(xué)基金項目(No.81560607,81360251) 新疆重大疾病醫(yī)學(xué)重點實驗室開放課題(No.SKLIB-XJMDR-2012-2) 新疆維吾爾自治區(qū)包蟲病基礎(chǔ)醫(yī)學(xué)重點實驗室開放課題(No.XJDX0202-2013-10)
【分類號】：R383.3

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