伯氏疟原虫氯喹敏感株和抗性株在疟色素形成和致病性上的差异

目的：研究伯氏疟原虫氯喹敏感株（Ｎ）和抗性株（ＲＣ）在疟色素形成和致病性上的差异。方法：用伯氏疟原虫氯喹敏感株和抗性株分别感染ＩＲＣ小鼠。实验分为５组：正常对照组（ＮＣ），氯喹治疗对照组（ＣＣ），Ｎ株感染组（Ｎ），ＲＣ株感染组（ＲＣ）和ＲＣ株感染加氯喹治疗组（ＲＣＣ），比较各组间末梢血中疟原虫的形态、原虫血症、肝脏组织学及超微结构的改变。结果：Ｎ组肝细胞损害较严重，细胞内线粒体肿胀融合，溶酶体增多，肝血窦内疟原虫少见。ＲＣ组炎症反应较突出，主要为单核细胞浸润以及枯否细胞活跃，大滋养体和裂殖体在肝血窦滞留；肝细胞损害较轻，表现为线粒体增生、肿胀及空泡化。Ｎ株疟原虫富含内食物泡，其内有疟色素颗粒，被寄生红细胞结构较完整；而ＲＣ株疟原虫外食物泡较多，位于疟原虫外围的红细胞胞质内，被寄生的红细胞呈蜂窝样改变，食物泡内无疟色素。结论：ＲＣ株疟原虫可能改变了原敏感株（Ｎ株）对血红蛋白的摄取和消化方式，从而阻碍了疟色素形成；Ｎ株和ＲＣ株疟原虫可能因诱导宿主免疫反应的明显差异。

伯氏疟原虫氯喹敏感株和抗性株虫体食物泡和疟色素形态及形成的比较

目的:了解伯氏疟原虫氯喹敏感株(N)和抗性株(RC)红内期虫体在抗药性、致病力和诱导免疫应答方面差异的形态学基础。方法:应用超薄切片和透射电镜技术,比较N株和RC株虫体食物泡和疟色素形态及形成的差异。结果:N株滋养体具有单一的、大型的食物泡,疟色素位于滋养体周边的质膜下;在裂体生殖中,疟色素发生聚合和中心化。RC株滋养体食物泡少见,其中多数虫体形成多个微型单层膜的食物泡样结构;疟色素形成明显少于N株滋养体;而且在裂体生殖中,未见疟色素聚合和中心化。结论:伯氏疟原虫RC株长期在氯喹压力下,形成了微型食物泡样结构的摄食方式,具有与N株疟原虫不同的对游离血红素的解毒机制,这可能是伯氏疟原虫N株和RC株在抗药性、致病力和诱导宿主免疫应答方面差异的基础。

Macrophage Inflammatory Protein-lalpha mediates Matrix Metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment

Objective:To investigate the role of macrophage inflammatory protein-1alpha(MIP-1 alpha) in the detrimental enhancement of matrix mnetalloproteinase-9(MMP-9) expression,release and activity induced by phagocytosis of malarial pigment(haemozoin,HZ) in human monocytes. Methods:Human adherent monocytes were unfed/fed with native HZ for 2 h.After 24 hours. MIP-1 alpha production was evaluated by ELISA in cell supernatants.Alternatively.HZunfed /fed monocytes were treated in presence/absence of anti-human MIP-1 alpha blocking antibodies or recombinant human MIP-lalpha for 15 h(RNA studies) or 24 h(protein studies): therefore,MMP-9 mRNA expression was evaluated in cell lysatcs by Real Time RT-PCR,whereas proMMP-9 and active MMP-9 protein release were measured in cell supernatants by Western blotting and gelatin zvmography.Results:Phagocytosis of HZ by human monocytes increased production of MIP-1 alpha.mRNA expression of MMP-9 and protein release of proMMP-9 and active MMP-9.All the HZ-enbancing effects on MMP-9 were abrogated by anti-human MIP- 1 alpha blocking antibodies and mimicked by recombinant human MIP-l alpha.Conclusions: The present work suggests a role for MIP-lalpha in the HZ-dependent enhancement of MMP-9 expression,release and activity observed in human monocytes.higbligbtiug new detrimental effects of HZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.

青蒿琥酯复方组合对实验性脑型疟及其神经损伤的保护作用

脑型疟（cerebral malaria,CM）是非洲5岁以下儿童死亡的主要原因,且幸存儿童可出现严重的神经系统后遗症,青蒿琥酯对CM的临床治疗取得了突破性进展,但CM高死亡率、高致残率的临床问题仍未得到完全解决。该研究通过伯氏疟原虫Pb ANKA（Plasmodium berghei ANKA）感染C57BL/6小鼠建立实验性脑型疟（experimental cerebral malaria,ECM）模型,通过比较原虫血症水平、存活率、ECM昏迷及行为学评分、脑微血管阻塞、肝组织疟色素沉积及体温、体质量等,探讨青蒿琥酯复方组合的抗脑型疟作用。结果表明,青蒿琥酯复方组合能提高Pb ANKA感染小鼠的生存率,降低原虫血症水平,有效改善ECM神经损伤症状,减轻脑血管阻塞和肝脏疟色素沉积,对体温、体质量等基础指标也有明显改善作用。结果表明了青蒿琥酯复方组合对ECM所致病理改变和神经损伤的改善作用,有望为人类CM临床辅助治疗提供实验依据。