Xiao Shu-Hua, Zhang Chao-Wei
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2013 Apr;31(2):81-6.
To explore whether mefloquine possesses the effect on granuloma formation induced by Schistosoma japonicum eggs.
Seventeen out of twenty-eight mice infected with 20 S. japonicum cercariae for 35 days were treated orally with mefloquine at a single dose of 200 mg/kg, and groups of 2-3 mice were sacrificed at various intervals post-treatment. The livers removed from each group of mice were fixed in 10% formaldehyde. While the remained 11 untreated mice divided into 6 groups (1-2 mice per group) were sacrificed at the same time periods as groups of mice treated with mefloquine, and their livers served as untreated corresponding controls. The granulomas with single egg in the center were counted and their diameters were measured using an ocular micrometer. The liver tissue sections were stained with hematoxylin and eosin (HE), Foot's or Mallory's methods for observation on histopathological alteration of egg granulomas, and on the appearance of reticular and collagen fibers within the granulomas.
After infected mice were treated with mefloquine for 3, 7, 14, 21, 28 and 35 days, i.e., 38, 42, 49, 56, 63, and 70 days post-infection, the mean diameters of granuloma with single egg measured in the liver tissues section were (161 +/- 19), (175 +/- 13), (195 +/- 9), (171 +/- 40), (180 +/- 13), and (145 +/- 25) microm, respectively, and each of them was significantly lower than that of its corresponding control group of (189 +/- 18), (197 +/- 11), (211 +/- 12), (208 +/- 19), (203 +/- 16), and (207 +/- 36) microm (P < 0.01 or P < 0.05). Histopathological observation showed that in mice treated with mefloquine, the eosinophil-predominant inflammatory cells around the egg granuloma were sustained to 14-21 d post treatment (49-56 d post infection), which was significantly different from the corresponding control groups that all the eggs were surrounded by fibroblasts at 42 d post infection. Up to 28-35 d post treatment (63-70 d post infection), the boundary of egg granulomas distributed in the liver tissues of mefloquine treated groups was nearer in comparison to the corresponding control groups. Further observation on the reticular and collagen fibers within the egg granulomas by using specially staining methods demonstrated that in groups of mice treated with mefloquine for 2 weeks, the emergence and amount of the two kinds of fibers were delayed and less in comparison with corresponding control groups. After infected mice treated with mefloquine for 21 d (56 d post infection), the amount of the two kinds of fibers revealed in some egg granulomas was similar to the corresponding control group, but no further increase in the amount of the fibers, and seldom spread over the boundary of egg granuloma were seen 28 d and 35 d after treatment (63 d and 60 d post infection). While in corresponding control groups, the two kinds of fibers increased continuously with time post infection to become thick, and spread over the boundary of granuloma to further interconnect with the fibers stretched from the adjacent granuloma, and separate the liver tissue to form the grid-like structure.
Preliminary observation demonstrates that mefloquine possesses suppressive effect on granuloma formation induced by S. japonicum eggs.
探讨甲氟喹对日本血吸虫虫卵诱导的肉芽肿形成是否具有影响。
28只感染20条日本血吸虫尾蚴35天的小鼠中,17只小鼠以200mg/kg的单剂量口服甲氟喹进行治疗,在治疗后的不同时间间隔处死2 - 3只小鼠为一组。从每组小鼠取出的肝脏用10%甲醛固定。其余11只未治疗的小鼠分为6组(每组1 - 2只),在与甲氟喹治疗组小鼠相同的时间段处死,其肝脏作为未治疗的相应对照组。计数中央有单个虫卵的肉芽肿,并使用目镜测微计测量其直径。肝组织切片用苏木精和伊红(HE)、Foot氏或马洛里氏方法染色,以观察虫卵肉芽肿的组织病理学改变以及肉芽肿内网状纤维和胶原纤维的外观。
感染小鼠经甲氟喹治疗3、7、14、21、28和35天,即感染后38、42、49、56、63和70天,肝组织切片中测量的单个虫卵肉芽肿的平均直径分别为(161±19)、(175±13)、(195±9)(171±40)、(180±13)和(145±25)微米,且每组均显著低于其相应对照组的(189±18)、(197±11)、(211±12)、(208±19)、(203±16)和(207±36)微米(P<0.01或P<0.05)。组织病理学观察显示,经甲氟喹治疗的小鼠,虫卵肉芽肿周围以嗜酸性粒细胞为主的炎性细胞持续至治疗后14 - 21天(感染后49 - 56天),这与相应对照组在感染后42天所有虫卵均被成纤维细胞包围显著不同。至治疗后28 - 35天(感染后63 - 70天),甲氟喹治疗组肝组织中分布的虫卵肉芽肿边界相较于相应对照组更近。采用特殊染色方法对虫卵肉芽肿内的网状纤维和胶原纤维进一步观察表明,经甲氟喹治疗2周的小鼠组,与相应对照组相比两种纤维的出现和数量延迟且较少。感染小鼠经甲氟喹治疗21天(感染后56天),部分虫卵肉芽肿中显示的两种纤维数量与相应对照组相似,但纤维数量未进一步增加,治疗后28天和35天(感染后63天和70天)很少见纤维延伸至虫卵肉芽肿边界。而在相应对照组中,两种纤维随感染后时间持续增加变粗,并延伸至肉芽肿边界与相邻肉芽肿伸出纤维进一步相互连接,分隔肝组织形成网格状结构。
初步观察表明甲氟喹对日本血吸虫虫卵诱导的肉芽肿形成具有抑制作用。