蒿甲醚对小鼠体内伯氏疟原虫超微结构的影响

体重18～22g非纯系昆明小鼠腹腔接种1×10~7个感染伯氏疟原虫红细胞。原虫感染率上升至11.7～17.5％时,腹腔单次注射蒿甲醚油剂,分5mg/kg和25mg/kg两剂量组。给药后,和给药后1、2、4、8、16及24h取小鼠尾血,按常规做超薄切片,透射电镜观察。     

伯氏疟原虫氯喹抗性逆转的实验观察

目的 寻找伯氏疟原虫氯喹抗性逆转剂.方法 将健康昆明小鼠72只(雌、雄各半)每只腹腔注射0.2 ml伯氏疟原虫ANKA株氯喹敏感系(chloroquine sensitive,CS)或由其选育的高抗氯喹系(chloroquine resistance,CR),按下述随机分组后灌胃给药治疗,观察各组疗效.(1)小鼠感染CS疟原虫30 min后随机均分为4组,每组6只,给D-6182{(Z,Z)-N,N,N-三甲基-2,3-双[(1-氧代-9-十八碳烯酸)-氧代]-1-丙胺基盐酸盐|、C-2832[胆畄醇-3-N-(二甲胺基乙基)氨甲酸酯]、Ket(酮替酚)、0.1%西黄蓍胶(对照组),连续灌药5 d.于D1至D7每天每鼠取尾血涂片作常规镜检,确定各实验组的原虫血症.(2)小鼠感染CR疟原虫后第3天随机均分为8组,每组6只,给D-6182、C-2832、Ket组、氯喹组、0.1%西黄蓍胶对照组及给予D-6182、C-2832、Ket后2 h再加灌服小剂量12 mg/(kg·d)氯喹(5%ED90),连续5 d.每鼠于D4至D7每天取尾血涂片作常规镜检,确定各实验组的原虫血症,并计算各组的原虫减虫率.结果 (1)感染伯氏疟原虫CS株的小鼠,分别灌服80 mg/(kg·d)D-6182、120 mg/(kg·d)C-2832或10 mg/(kg·d)Ket连续5 d,各给药组与对照组小鼠的原虫感染率自D1至D4逐日上升,至D4达峰值,D5时对照组小鼠原虫感染率继续上升,而各给药组维持在D4的峰值水平.(2)感染伯氏疟原虫CR株的小鼠给适宜剂量的C-2832、D-6182或Ket后2 h加灌服小剂量氯喹12 mg/(kg·d)(5%ED90),此后连续5 d(D3-D7),于D4原虫减虫率可达到97.77%、99.28%或96.73%,而在D7可达到99.81%、98.87%或100.00%.结论 C-2832和D-6182两种化合物对伯氏疟原虫CR株感染小鼠的氯喹抗性具有逆转作用,其逆转能力与Ket相当.     

三吡萘啶在动物模型上的长效预防抗疟作用

本文报告了用 4.5倍ED_(50) 剂量的三吡萘啶游离碱喂饲小鼠,给药后 20 d再用伯氏疟原虫 ANKA 株原虫1×10~7个攻击,小鼠全部获得保护。三吡萘啶磷酸盐对鼠疟的滞效作用虽较其游离碱及哌喹磷酸盐稍好,但进行猴疟实验喂药时易引起恒河猴呕吐,难于准确计算给药量。三吡萘啶羟萘酸盐对鼠疟的滞效抗疟作用则不如其磷酸盐,也不如其游离碱。三吡萘啶游离碱总剂量为200 mg/kg,对食蟹猴疟原虫B株确有 20 d的滞效抗疟作用,但总剂量降至 100 mg/kg 时,其滞效作用即明显下降。总之,三吡萘啶游离碱对猴疟的长效抗疟作用似较哌喹稍逊。     

瑞香素杀疟原虫裂殖体的作用

[目的 ]研究中药瑞香素在体外和体内的杀裂殖体作用。 [方法 ]在恶性疟原虫FCCl株常规体外培养中测试瑞香素杀裂殖体活性 ,并按“四天抑制性试验”在感染伯氏疟原虫ANKA株的小鼠中测定不同剂量瑞香素的体内抗疟活性。 [结果 ]体外试验中瑞香素在 1～ 10 μmol L剂量范围内有明显杀灭裂殖体作用 ,而体内试验中按D4减虫率与感染鼠在 30d内的平均生存天数评价 ,5 0或 10 0mg kg .d- 1 × 4d瑞香素灌胃以及 10 ,5 0或 10 0mg kg.d- 1 × 4d瑞香素腹腔注射给药在伯氏鼠疟原虫ANKA株感染鼠中的抗疟作用与 10mg kg .d- 1 × 4d氯喹 (CQ)灌胃的疗效相似。 [结论 ]瑞香素在体外和体内均有一定的杀裂殖体作用。     

伯氏疟原虫和约氏疟原虫经输血感染在小鼠体内自然消长的观察

约氏疟原虫对小鼠具有高度的感染力,每鼠接种5个感染疟原虫的红细胞时,66.6％的小鼠出现原虫血症。伯氏疟原虫的接种剂量如低于1×10~6个感染疟原虫的红细胞,只能使部分小鼠出现原虫血症。两种鼠症原虫用相同剂量接种小鼠后,原虫血症的出现时间前者早于后者。接种约氏疟原虫的阳性小鼠能自然转阴,不引起小鼠死亡;但接种伯氏疟原虫后的阳性小鼠则不能自然转阴。     

咯萘啶对鼠疟原虫红内期裂殖体的持效作用

小鼠在腹腔注射(D_0)约氏鼠疟原虫前15天(D_(-15))肌注或灌胃咯萘啶100mg/kg,可使大部分小鼠不出现原虫血症。D_(-10)肌注或灌胃10mg/kg,D_(-5)肌注5mg/kg或D_(-4)灌胃5mg/kg亦有抑制原虫血症的作用。因该株原虫对氯喹具固有的抗药性,故即使在D_(-3)肌注或灌胃400mg/kg氯喹(>(2/3)LD_(50))亦不能保护小鼠不受感染。 应用伯氏鼠疟原虫的实验证明:咯萘啶杀裂殖体的持效作用明显比氯喹的为长。咯萘啶剂量为10mg/kg(ED_(50)的1.47倍,或LD_(50)的0.7％)时,D_(-6)灌胃一剂即能抑制原虫血症的出现,但相应剂量的氯喹67mg/kg(ED_(50)的1.47倍,或LD_(50)的10％),仅于D_(-2)给药有微效。     

咯萘啶、阿莫地喹、甲氟喹及青蒿素对伯氏疟原虫的疗效

用4天抑制试验法给感染伯氏疟原虫ANKA株小鼠灌胃咯萘啶12.5mg/kg·d或阿莫地喹25mg/kg·d均能完全杀灭原虫;甲氟喹25mg/kg·d或青蒿素100mg/kg·d虽有抑制作用但治愈率仅为50％及0％。咯萘啶12.5mg/kg·d对中度抗氯喹的NS系原虫亦有明显作用,洽愈率70％,而阿莫地喹100mg/kg·d、甲氟喹100mg/kg·d及青蒿素200mg/kg·d均无治愈鼠,示后3种药与氯喹有不同程度的交叉抗性。上述剂量的阿莫地喹、甲氟喹和青蒿素对高度抗咯萘啶的伯氏疟原虫无明显抑制作用,示它们与咯萘啶有交叉抗性。     

瑞香素结构衍生物体内外抗疟活性的研究

目的 通过体外试验和鼠疟(Plamodium berghei)动物模型观察瑞香素结构衍生物的抗疟作用.方法 通过光学显微镜镜检和微量荧光法两种体外筛选系统筛检瑞香素类衍生物对恶性疟原虫(Plamodium falciparum)的体外抗疟作用;对体外筛检抗疟活性高的化合物,采用WHO推荐的"四天抑制试验"测定其对鼠伯氏疟原虫(ANKA株)的抗疟作用.结果 通过体外筛选系统筛选出DA78与DA79两种新型的瑞香素类抗疟化合物,两者的IC50分别为7.6 μmol/L和1.4 μmol/L,其体外抗疟活性与瑞香素在同一统计学水平(P＞0.05);体内试验伯氏鼠疟原虫ANKA株感染鼠,DA78 1、10、50、75 mg/kg·d×4 d剂量组D4减虫率与空白对照组比较差异有显著性(P＜0.01),而DA79 50或75 mg/kg·d×4 d剂量组D4减虫率与对照组相比较差异有显著性(P＜0.05),DA78 10或75 mg/kg·d×4 d剂量组D4减虫率高于同剂量的瑞香素组(P＜0.05).结论 以DA78与DA79为代表的瑞香素类衍生物作为一类新型的抗疟化合物,在体外和体内试验中均显示出一定的抗疟活性,为寻求更有效的抗疟化合物提供了方向和理论依据.     

妊娠期使用司他夫定对ICR母鼠和子鼠肝细胞线粒体DNA D Loop的影响

目的研究ICR小鼠妊娠期使用司他夫定(d4T)后对亲代和子代小鼠肝脏线粒体DNA D loop区序列的影响。方法 20只ICR雌性小鼠分为2组,每组10只,从妊娠期第1 d起,每天分别以d4T 20 mg/kg和10 mg/kg灌胃至分娩。分娩后处死母鼠和子鼠,取肝脏,提取DNA,PCR扩增线粒体DNA D Loop区494 bp片段并测序,与参考序列(ref|NC_005089.1)比对,观察序列有无变化。结果母鼠和子鼠肝细胞线粒体DNA的D loop区序列未检测到突变位点。结论妊娠期使用人类相当治疗剂量的d4T不会导致小鼠肝脏细胞线粒体DNA D loop序列突变增加。d4T对线粒体DNA的影响需要进一步研究。     

纯品枸杞多糖对小鼠免疫功能的影响1

将纯品枸杞多糖分为每天5 mg/kg、10 mg/kg、50 mg/kg及100 mg/kg等5个不同剂量的实验组,灌喂小鼠,观察其对小鼠免疫功能的影响。结果显示,纯品枸杞多糖各剂量组对机体均有良好的免疫促进作用,低剂量(每天5～20 mg/kg)较高剂量(每天50～100 mg/kg)显示出更明显的免疫增强效应。尤以每天10 mg/kg剂量效果最佳,非特异性免疫和特异性免疫等项指标与其他各剂量组比较差异有极显著性。     

蒿甲醚与瑞香素伍用对感染伯氏疟原虫小鼠的治疗作用

目的　研究蒿甲醚与瑞香素伍用(A+D)对感染伯氏疟原虫ANKA株小鼠的疗效及其联合作用方式。　方法　按“四天抑制法”d0 感染,d0 ～d3 给药,每天1次,d4涂薄血膜检查,并计算d4减虫率及各药丰数有效置(ED50),用等效应图解法分析A+D的合并作用。　结果　蒿甲醚0.4mg/(kg·d)× 4d的d4减虫率与对照组相比差异无显著性 ;[A0 .4mg/(kg·d) +D7.7mg/(kg·d) ]× 4d的抗疟效果提高 ,与对照组相比差异有显著性(P<0.05)。A+D各组的ED50均低于单用药组;不同配伍比例的R值皆大于0.4,小于2.7(0.4     

Tissue schizontocidal effect of trifluoroacetyl primaquine in Plasmodium yoelii infected mice and Plasmodium cynomolgi infected monkeys

Trifluoroacetyl primaquine oxalate (M8506) was compared with primaquine phosphate for tissue schizontocidal action in rodent and simian malaria. In Plasmodium yoelii sporozoites infected mice, the causal prophylactic effects of M8506 at 5, 10 and 20 mg(base)/kg were 56.7%, 87.2% and 100%, respectively, comparable to those of primaquine (54.4%, 90.8% and 100%). In P. cynomolgi sporozoites infected rhesus monkeys 4 dosage regimens of the two agents were compared for radical curative effect. On the first day of treatment pyronaridine phosphate 10 mg(base)/kg twice a day were intramuscularly injected to eliminate erythrocytic stages of P. cynomolgi. At the dosage of 3.0 mg(base)/kg/day x 3, both M8506 and primaquine radically cured the monkeys. At 0.75 mg/kg/day x 3, 12 of 13 (92.3%) monkeys cured by M8506, 5 of 9 (55.6%) cured by primaquine. At 1.5 and 0.375 mg/kg/day x 3, the radical curative effects of M8506 were also better than those of primaquine. Since the toxicity of M8506 was significantly milder in mice, rats and dogs than that of primaquine, M8506 has potential as a tissue schizontocide.     

Daphnetin: a novel antimalarial agent with in vitro and in vivo activity.

Daphnetin is a dihydroxycoumarin that is being used in China for the treatment of coagulation disorders. It is also a chelator and an antioxidant. In vitro, daphnetin causes a 50% inhibition (IC50) of 3H-hypoxanthine incorporation by Plasmodium falciparum at concentrations between 25 and 40 microM. Several related compounds, such as scopoletin, 2, 3-dihydroxybenzoic acid and 3, 4-dihydroxybenzoic acid show no inhibitory activity. The antimalarial activity of daphnetin is inhibited by the addition of iron. Daphnetin does not appear to be an oxidant drug, since it does not spontaneously generate superoxide in vitro. However, it does alkylate bovine serum albumin when incubated in the presence of iron. In vivo, daphnetin significantly prolongs survival of P. yoelli-infected mice.     

瑞香素体外抗疟作用与其铁螯合能力的关系

目的　研究瑞香素体外抗疟作用与其铁螯合能力的关系。　方法　在恶性疟原虫FCC1株常规方法体外培养中检测瑞香素和去铁胺杀裂殖体活性。利用荧光探针calcein测定瑞香素和去铁胺的铁螯合能力。　结果　与强铁螯合剂去铁胺相比 ,瑞香素具有中度的铁螯合能力。体外实验中瑞香素在 0～ 12 μmol/L剂量范围内有剂量依赖性的杀裂殖体活性。瑞香素与Fe2 + 按 2∶1混合后 ,抗疟作用明显下降。　结论　瑞香素的抗疟作用与它的铁螯合能力有关。     

约氏疟原虫感染大鼠和小鼠的红外期研究

约氏疟原虫约氏亚种的子抱子经尾静脉接种大鼠和三株小鼠(ICR/JCL,C57BL,KM株)后42h,在大鼠和小鼠的肝连续切片中均查见红外期裂殖体(EE裂殖体),但在KM鼠株的切片中,正常的EE裂殖体甚少。不论宿主同否,EE裂殖体均大小不等,呈圆形、椭圆形或其他形状,分化程度不同,发育不完全同步。大鼠肝中的EE裂殖体可看到明显的外膜,周围并出现细胞反应。ICR/JCL、C57BL鼠株和大鼠肝中的EE裂殖体均较KM鼠株发育良好,数量较多,但大鼠中的红内期迅速消失。结果表明;ICR/JCL和C57BL鼠株用作约氏疟原虫—斯氏按蚊系统鼠疟模型的宿主较合适。     

The effect of pentostam and cimetidine on the development of leishmaniasis (Leishmania mexicana amazonensis) and concomitant malaria (Plasmodium yoelii)

BALB/c mice were infected with Leishmania mexicana amazonensis and/or Plasmodium yoelii in order to determine the impact of multiple parasitic infection on the efficacy of chemotherapeutic agents. Uninfected, P. yoelii-infected, L.m. amazonensis-infected, and L.m. amazonensis and P. yoelii-infected mice were inoculated with cimetidine (80 mg kg-1 day-1) or pentostam (200 mg kg-1 day-1) once a day for an initial 20-day period, and once a week thereafter. Leishmania mexicana amazonensis lesion development and P. yoelii parasitaemia were the criteria used to assay disease severity. Mice infected with both P. yoelii and L.m. amazonensis developed more severe disease than did animals infected with either parasite alone. Cimetidine and pentostam each slowed the development of L.m. amazonensis in animals infected with only that parasite and in animals infected with both P. yoelli and L.m. amazonensis. However, mice treated with pentostam developed more severe P. yoelii infections than did control animals, whereas cimetidine significantly reduced P. yoelii parasitaemia in all instances.     

Chloroquine efficacy in Plasmodium berghei NK65-infected ICR mice, with reference to the influence of initial parasite load and starting day of drug administration on the outcome of treatment

We examined whether the initial number of parasites inoculated and the starting day of medication post-infection influenced the antimalarial efficacy of chloroquine (CQ) against Plasmodium berghei NK65 infection in ICR mice. Male ICR mice were inoculated intraperitoneally with 1 x 10(5), 1x10(6), 1 x 10(7), 1 x 10(8) P. berghei NK65-parasitized erythrocytes (pRBC). In the treated group, all mice received an oral dose of 20 mg/kg of CQ base for 4 days starting on day 0 after infection. From day 3, Giemsa-stained thin blood smears from tail vein blood were used to assess parasitemia. Mice in the untreated control in each group showed a progressive increase in parasitemia leading to death. Treatment of mice, inoculated with 1 x 10(5), 1 x 10(6) and 1 x 10(7) pRBC, with CQ showed a marked effect. All the mice survived during the experiment. During the observation period, malaria parasites could not be detected on microscopic examination. Conversely, mice inoculated with 1 x 10(8) pRBC showed little response to CQ treatment, and all mice showed a progressive increase in parasitemia and ultimately died. In another experiment, mice infected with 1 x 10(3) and 1x 10(5) pRBC were treated with an oral four-day dosage of 20 mg/kg of CQ base from days 2, 3 or 4 post-infection. Treatment of mice, inoculated with 1 x 10(3) pRBC, with CQ from days 2 and 3 showed a marked effect. All mice survived during the experiment. However, treatment from day 4 showed a limited derease in parasitemia and all the mice ultimately died. On the other hand, treatment from day 2 showed a marked effect against 1 x 10(5) P. berghei NK65-infected mice, but treatment from days 3 or 4 was only slightly effective and all the mice died with an increasing parasitemia. The present results indicate that in in vivo antimalarial drug-assay systems, several factors, sush as initial parasite load and starting time of treatment may influence the drug response in the host.     

CD4+CD25+调节性T细胞对疟原虫感染鼠结局的影响

目的探讨CD4^＋CD25^＋调节性T细胞与疟原虫感染鼠结局的相关性。方法分别以致死型约氏疟原虫（Plasmodium yoelii17XL）和夏氏疟原虫（Plasmodium chabaudi chabaudi AS）感染BALB/c小鼠，制备薄血膜，Giemsa染色，镜检计数红细胞感染率;以流式细胞术检测脾细胞悬液中CD4^＋CD25^＋T细胞百分率。结果P.yoelii 17XL感染鼠的原虫血症于感染后第6 d达到峰值水平（55.5%），并于当日和次日内全部死亡，CD4＋CD25＋T细胞水平于感染后第1 d迅速升高，且于感染后第5 d达到峰值水平（23.6%）;P.c.chabaudiAS感染鼠的原虫血症在感染后第8 d达到峰值水平（38.2%）后迅速下降，并于感染后第15 d左右全部自愈，CD4^＋CD25^＋T细胞水平也于感染后第1 d开始升高，但其感染后第5 d的峰值水平（13.8%）显著低于P.yoelii 17XL感染小鼠（P〈0.01）。结论CD4＋CD25＋T细胞活化水平可显著影响疟原虫感染鼠的结局。     

瑞香素类抗疟化合物的筛选及其靶分子研究

目的 通过体外试验和鼠疟动物模型筛选瑞香素结构衍生物的抗疟作用,确定瑞香素类抗疟化合物对恶性疟原虫抗疟作用的靶分子.主要研究内容及方法 (1)在瑞香素基本结构的基础上设计并合成瑞香素的结构衍生物;(2)通过光学显微镜镜检和微量荧光法两种体外筛选系统筛检瑞香素类衍生物对恶性疟原虫的体外抗疟作用;(3)对体外筛检抗疟活性高的化合物,采用WHO推荐的四天抑制试验测定其对鼠伯氏疟原虫(ANKA株)的抗疟作用;(4)以电子自旋共振法测定瑞香素类抗疟化合物对恶性疟原虫核糖核酸还原酶(ribonucleotide reductase,RNR)活性的影响;(5)采用紫外分光光度法测定瑞香素类抗疟化合物对恶性疟原虫细胞色素C氧化酶(cytochrome c oxidase,COX)活性的影响;(6)对体外同步培养的恶性疟原虫经瑞香素、DA78与DA79作用后,抽提总RNA,并合成相应的特异性引物,运用实时荧光PCR法测定瑞香素类抗疟化合物对恶性疟原虫的重要生物功能酶,如RNR、超氧化物歧化酶(superoxidase dismutase,SOD)及乳酸脱氢酶(lactate dehydrogenase,L,DH)等基因表达的影响.结果 (1)在瑞香素结构的基础上,通过对7、8位羟基或相邻位点的修饰,共合成32种瑞香素结构衍生物.(2)通过体外筛选系统筛选出DA78与DA79两种新型的瑞香素类抗疟化合物,两者的IC50分别为7.6μmol/L、1.4μmoL/L,其体外抗疟活性与瑞香素的差别无统计学意义(P＞0.05);体内试验按D4减虫率评价,瑞香素、DA78与DA79灌胃给药在鼠伯氏疟原虫ANKA株感染小鼠中,DA79在1、10、50、75 ms/(kg·d)×4 d组与对照组1%西黄蓍胶相比较差异有统计学意义(P＜0.01),而DA78在50或75 mg/(kg·d)×4 d的抗疟作用与对照组相比较差异有统计学意义(P＜0.05);另外DA79在10或75 mg/(kg·d)×4 d的抗疟效果要优于同剂量的瑞香素(P＞0.05).(3)体外同步培养的恶性疟原虫经100μmol/L瑞香素2、4、8和12 h作用后,COX活性依次下降了0、6%、、73%和80%,在瑞香素浓度为100 nmoi/L、lμmoL/L、100 μmol/L与l mmol/L作用6 h后,COX活性依次下降了3%、31%、53%和84%(n=3),其活性随着瑞香素浓度的增高基本成线性降低,而当瑞香素的铁鳌合能力饱和后对COX活性的影响几乎消失;100 μmol/L DA78与DA79作用2、4、8和12 h后,COX的活性依次下降了0、2%、11%、9%与7%、13%、17%、32%,在DA78、DA79浓度为100 nmol/L、1 μmol/L、100 μmol/L与1 mmol/L作用6 h后,COX活性依次下降了0、0、4%、13%与1%、4%、15%、29%,其活性随着DA78或DA79浓度的增高基本成线性降低,其中DA79对COX的抑制作用高于DA78,但两者均低于瑞香素对COX的作用(n=3,P＜0.01).(4)体外同步培养的恶性疟原虫经瑞香素、DA78与DA79作用后.以电子自旋共振法测定不同时间恶性疟原虫酪氨酸的量以反映RNR的活性,经100 μmol/L瑞香素作用1、2、3和4 h后,相对于对照组的值RNR的活性依次为其值的93%、49%、31%和25%,在瑞香素浓度为100 nmol/L、1 μmol/L、100 Vanol/L与1 mmoL/L作用6 h后,相对于对照组的值RNR的活性依次为其值的97%、69%、42%和7%;RNR的活性随着瑞香素浓度的增高而降低,但并非呈线性相关.当瑞香索铁鳌合能力饱和后,恶性疟原虫RNR活性几乎未受影响(n=3,P＞0.05).经100μmot/L DA78与DA79作用1、2、3和4 h后,相对于对照组的值恶性疟原虫RNR的活性依次为其值的98%、96%、87%、71%与93%、44%、41%、23%,DA79对RNR活性的抑制作用高于同剂量相同作用时间DA78的作用(n=3,P＞0.01),DA79与瑞香素在体外对恶性疟原虫RNR抑制作用的差别无统计学意义(n=3,P＞0.05);在DA78与DA79浓度为100 nmol/L、1μmol/L、100μmol/L与1 mmol/L.,作用6 h后,相对于对照组的值RNR的活性依次为其值的100%、92%、64%、61%与97%、48%、25%、4%,DA79对RNR活性的抑制作用高于同剂量DA78的作用(n=3,P＜0.01),并且高于同剂量瑞香素对RNR活性的抑制作用(n=3,P＜0.05).(5)恶性疟原虫体外经瑞香素、DA78与DA79作用后,LDH、SOD与RNR 3种基因扩增的标准曲线,在105～109 copies/ml范围内标准曲线呈良好的线性关系,其基因扩增产物的标准曲线的r2依次为0.9907、0.9983、0.9975.根据标准曲线计算各组样品3种基因的原始拷贝数来比较各组3种基因表达量的差异,不同处理组对恶性疟原虫LDH基因的表达无显著性抑制作用(n=3,P＞0.05),而且各组间差异无统计学意义(n=3,P＞0.05);瑞香素、DA78与DA79对恶性疟原虫RNR基因的表达均有抑制作用;只有瑞香素对恶性疟原虫SOD基因表达产生抑制作用,其他各组无显著性抑制作用;但瑞香素的铁螯合能力饱和后,对上述3种基因的表达均未产生显著性抑制作用(n=3,P＞0.05).结论以DA78与DA79为代表的瑞香素类衍生物作为一类新型的抗疟化合物,在体外和体内试验中均显示出一定的抗疟活性;RNR很可能作为瑞香素类抗疟化合物抗疟作用的靶分子.本研究首次发现两种瑞香素结构衍生物DA78与DA79具有与瑞香素同一水平的抗疟活性,为寻求更有效的抗疟化合物提供了方向,并利用分子生物学方法对瑞香素抗疟化合物抗疟作用的靶分子进行了筛选与研究,初步确定了RNR作为瑞香素类抗疟化合物抗疟作用的靶标,为今后瑞香素类抗疟药物的进一步开发提供了理论依据.