双氢青蒿素对体外蓝氏贾第鞭毛虫的损伤

目的 探讨双氢青蒿素（DHA）对蓝氏贾第鞭毛虫的损伤作用。 方法 用含不同浓度DHA的TYI-S-33培养基培养蓝氏贾第鞭毛虫滋养体。分别在光镜和电镜下观察药物作用后虫体的形态结构变化。 结果 随着药物作用时间延长和浓度的增加，虫体死亡率增高。在同一时间内随着药物浓度的增高，虫体死亡率升高(P<0.01)。DHA浓度为100 μg/ml, 作用12 h，虫体死亡率为46.6%，浓度增至200 μg/ml时, 虫体死亡率为100%；同一药物浓度随着作用时间延长, 虫体死亡率也升高（P<0.05），当浓度为100 μg/ml,作用12 h，虫体死亡率为46.6%，作用24 h死亡率增至100%。药物作用后24、48和72 h光镜下观察结果显示，虫体变形、肿胀、出现空泡、失去正常的瓢形运动能力；鞭毛摆动迟缓或停止运动。电镜下观察，见虫体变形、肿胀、细胞膜崩解、脱落，表面出现胞质突起；细胞质内核糖体溶解，出现空泡；吸器失去凹状结构，隆起变成大泡；核染色质稀疏，核周间隙变宽，并出现异形核。 结论 DHA对蓝氏贾第鞭毛虫的质膜及细胞骨架有较强的损伤作用。

Effect of Dihydroartemisinin on Ultrastructure of Giardia Lamblia in vitro

OBJECTIVE: To study the in vitro effect of dihydroartemisinin (DHA) on Giardia lamblia. METHODS: Trophozoites of G. lamblia were cultivated with modified TYI-S-33 medium that contains dihydroartemisinin (DHA). The trophozoites were morphologically observed respectively with light and electron microscopes after treated with the drug. RESULTS: The mortality increased with the prolongation of the time of the drug action and the increase of drug concentration (P<0.01). While at the same concentration of 100 microg/ml, the mortality increased from 46.6% for 12 h to 100% for 24 h (P<0.05). For 12 h, the mortality of G. lamblia was from 46.6% at concentration of 100 microg/ml to 100% at 200microg/ml. Under optical microscope, deformation and swelling of the parasites were observed when treated with DHA for 12, 24 and 48 h. Movement of the flagella became slow or stopped. Under electron microscope, the trophozoites were swollen and deformed, vacuoles were seen in the cytoplasm, and the cell membrane ruptured and fell off. The cytoplasm protrusions appeared on the surface of the plasma membrane. The adhesive disc changed into large bubbles and the perinuclear space became wider and the deformed nucleus was seen. CONCLUSION: DHA shows a strong impairment on the plasma membrane and cytoskeleton of Giardia lamblia.