磺胺氯吡嗪钠复方对小鼠体内抗弓形虫疗效的观察

TREATMENT EFFECT OF COMPOUND SULFACHLOROPYRAZINE SODIUM ON ACUTE TOXOPLASMOSIS IN MICE

为进一步挖掘磺胺氯吡嗪钠的抗弓形虫疗效,本研究以磺胺嘧啶钠作为对照,观察磺胺氯吡嗪钠(sulfachloropyrazine sodium,SPZ)、黄芩苷、乳酸TMP、乙胺嘧啶和甘草单独使用时的体内外抗弓形虫效果,然后以SPZ-甘草-黄芩苷3种药物的复方制剂作为复方对照组,用叶酸合成双抑制的SPZ-乳酸TMP/乙胺嘧啶复方制剂对人工感染弓形虫RH株的KM小鼠进行体内治疗试验。体外试验表明,这6种药物均可较好地抑制弓形虫增殖;小鼠体内试验表明,单独使用SPZ(250 mg/kg、200 mg/kg)可保护部分小鼠存活(存活率分别为50%和25%),其他5种药物可不同程度地延长小鼠存活时间,但均不能避免小鼠死亡。在复方给药组(SPZ浓度为200 mg/kg),使用SPZ-乳酸TMP/乙胺嘧啶无明显的协同作用,使用SPZ-甘草-黄芩苷时疗效得到明显提高(小鼠存活率达到40%)。结果启示SPZ特别的治疗效果除了与其具有的通过干扰虫体叶酸代谢来抑制虫体繁殖的作用有关外,可能还与其他机制(如药物作用影响弓形虫调节宿主的免疫功能)有关。

To further explore the curative effect of sulfachloropyrazine sodium （SPZ） on Toxoplasma gondii, we tested single use of SPZ, baicalin, lactate TMP, pyrimethamine and glycyrrhiza against T.gondii both in vitro and in vivo and used sulfadiazine sodium（SDZ） as control. Then we used SPZ-glycyrrhiza-baicalin as control to test the combination effect of SPZ with lactate TMP or pyrimethamine, which blocked the synthesis of folic acid in double ways in KM mice artificially infected with T.gondii RH strain. The results showed that all 6 drugs showed inhibitory effect on the proliferation of T.gondii in vitro. The single dosages of SPZ （250 mg/kg or 200 mg/kg） protected some mice from death in acute toxoplasmosis as the survival rates were 50% and 25% in vivo. Other 5 drugs delayed the death but did not protect them from death. Combined administration use of SPZ （200 mg/kg） and lactate TMP or pyrimethamine had no obvious synergistic effect while compound SPZ-glycyrrhiza-baicalin significantly improved the survival rate up to 40%. The results suggested that the special therapeutic effect of SPZ not only inhibited the proliferation of T.gondii by by interfering the metabolism of folic acid, but also possibly had interaction with the host immunity.