目的 通过黄花蒿水提物干预感染青蒿素抗性虫株和哌喹抗性虫株的小鼠，从多角度评估其对抗性虫株 的治疗作用。方法 将小鼠分为空白组、模型组、阳性组及黄花蒿低、中、高剂量组，腹腔注射虫血复制鼠疟 模型，造模后 2 h 开始灌胃给药，连续给药 4 d。在第 4 天制作血涂片，计算小鼠感染率；计算肝脏、脾脏系 数并进行 HE 染色，对比组间组织病理学改变；采用 ELISA 法测定小鼠血清肿瘤坏死因子 α（TNF-α）、干扰素 γ（IFN-γ）、白细胞介素 6（IL-6）含量，以及肝脏组织液中细胞间黏附分子 1（ICAM-1）、血管细胞黏附分子 1 （VCAM-1）含量。结果 在黄花蒿水提物对青蒿素抗性株和哌喹抗性株药效实验中，与空白组比较，模型组小 鼠感染率、肝系数、脾系数、血清中 TNF-α、IFN-γ、IL-6 含量以及肝脏中 ICAM-1、VCAM-1 含量都显著升 高（P＜0.01），肝脾病理组织结构破坏显著，有明显疟色素沉积。与模型组比较，给药后各组感染率显著下降 （P＜0.01），肝脾病理结构改善，疟色素堆积减少。在青蒿素实验中，与青蒿素抗性模型组比较，给药后青蒿 素抗性黄花蒿中剂量组肝脏系数明显下降（P＜0.05），青蒿素抗性黄花蒿各剂量组的 TNF-α、IL-6、ICAM-1 水平明显下降（P＜0.05，P＜0.01），青蒿素抗性黄花蒿高剂量组的 IFN-γ 水平明显下降（P＜0.05），青蒿素抗 性黄花蒿低剂量组的 VCAM-1 水平明显下降（P＜0.05）。在哌喹实验中，与哌喹抗性模型组比较，给药后哌喹 抗性黄花蒿高剂量组脾脏系数显著降低（P＜0.05），哌喹抗性黄花蒿各剂量组的 TNF-α、IFN-γ、ICAM-1、 VCAM-1 水平明显下降（P＜0.05，P＜0.01），哌喹抗性黄花蒿低、高剂量组的 IL-6 水平明显下降（P＜0.05， P＜0.01）。结论 黄花蒿水提物对青蒿素抗性鼠疟和哌喹抗性鼠疟具有较好的杀虫作用，对疟疾有一定的治疗 作用，其治疗作用与减轻宿主炎症反应及免疫应答有关。

Objective To evaluate the therapeutic effects of aqueous extract of Artemisia annua L. on mice infected with artemisinin-resistant and piperaquine-resistant malaria parasites from multiple perspectives. Methods Mice were divided into blank，model，positive control，and low-，medium-，and high-dose Artemisia annua L. extract groups. A murine malaria model was established by intraperitoneal injection of infected blood，and oral administration began 2 hours post-modeling and continued for 4 days. On day 4，blood smears were prepared to calculate infection rates. Liver and spleen indices were calculated，and HE staining was performed to compare histopathological changes among groups. Serum levels of tumor necrosis factor-α （TNF-α），interferon-γ （IFN-γ），and interleukin-6 （IL-6），as well as liver tissue levels of intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1）， were measured using ELISA. Results In the efficacy experiments of Artemisia annua L. extract on artemisinin-resistant and piperaquine-resistant strains， compared with the blank group， the model group showed significantly increased infection rates，liver and spleen indices，serum TNF-α，IFN-γ，and IL-6 levels，and liver ICAM-1 and VCAM-1 levels （P＜0.01）. Severe histopathological damage and significant malaria pigment deposition were observed in the liver and spleen. Compared with the model group， all treatment groups exhibited significantly reduced infection rates （P＜0.01）， improved liver and spleen histopathology， and decreased malaria pigment accumulation. In the artemisinin experiment，compared with the artemisinin-resistant model group，the medium-dose Artemisia annua L. group showed a significant decrease in liver index （P＜0.05）. TNF-α，IL-6，and ICAM-1 levels were significantly reduced in all Artemisia annua L. dose groups （P＜0.05，P＜0.01），IFN-γ levels were significantly reduced in the high-dose group （P＜0.05）， and VCAM-1 levels were significantly reduced in the low-dose group （P＜0.05）. In the piperaquine experiment， compared with the piperaquine-resistant model group， the high-dose Artemisia annua L. group showed a significant reduction in spleen index （P＜0.05）. TNF-α，IFN-γ，ICAM-1，and VCAM-1 levels were significantly reduced in all Artemisia annua L. dose groups （P＜0.05， P＜0.01）， and IL-6 levels were significantly reduced in the low- and high-dose groups （P＜0.05，P＜0.01）. Conclusion The aqueous extract of Artemisia annua L. exhibits significant antimalarial effects against artemisinin-resistant and piperaquineresistant murine malaria， demonstrating therapeutic potential. Its efficacy is associated with alleviating host inflammatory responses and immune reactions.

R285.5

国家自然科学基金项目（82074301）；广州市科技计划项目（202206010066）