环孢素A体内抗日本血吸虫的实验研究  

Effect of cyclosporine A against Schistosoma japonicum in vivo

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作  者:胡奇丰[1] 柳建发[1] 

机构地区:[1]宁波大学医学院,宁波315211

出  处:《中国人兽共患病学报》2013年第9期862-868,共7页Chinese Journal of Zoonoses

基  金:浙江省科技厅基金(No:2009F80003);浙江省教育厅基金(No:Y200803083)~~

摘  要:目的观察环孢素A体内抗日本血吸虫的作用。方法 96只长爪沙鼠随机分8组,每组12只,A组为正常组,B组为模型组,C、D、E、F、G和H为治疗组。B、C、D、E、F、G和H组以腹部贴片法感染日本血吸虫尾蚴,每鼠感染120±2条尾蚴,于感染后(Day 0)和第3周(Day 21)对C、D、E、F、G和H各组分别给予3种不同剂量(10,20,50mg/kg·d)的环孢素A治疗,连续5天。5周后解剖全部沙鼠,经门静脉灌注收集成虫,计数虫荷,计算减虫率。收集到的虫体重新分组,扫描电镜(SEM)和透射电镜(TEM)观察虫体表面损害情况。病理学观察:取沙鼠肝脏和肠壁制作常规病理切片,然后进行HE染色观察虫卵肉芽肿面积大小,Masson染色观察肝脏纤维化程度。结果解剖结果显示,所有被感染沙鼠均有不同程度的虫卵结节产生,经环孢素A治疗后,各剂量组沙鼠肝脏虫卵结节均有减少,尤其高剂量组效果显著。HE染色结果显示,低剂量组肉芽肿面积与模型组相比没有明显改变,随着剂量的增加,肉芽肿面积减小,虫卵数量减少。高剂量组几乎未见虫卵。Masson染色同样显示随着剂量提高,纤维化程度逐渐减轻。应用扫描电镜可观察到未给药组雄、雌虫体体壁结果正常,凹窝、体棘和感觉乳突等清晰可见。用药后雄、雌虫体体壁表面破损严重,低剂量组可见表皮皱缩,凹凸不平;高剂量组虫体表皮溃烂,伴有大面积的脱落。透射电镜可见雌、雄虫体体壁产生大量空泡产生,体表细胞结构紊乱。结论环孢素A在体内可使童虫和成虫受损或致死,呈剂量依赖性,具有明显的抗日本血吸虫作用。To investigate the effect of cyclosporine A (CsA) against Schistosoma japonicum in vivo, 96 gerbils were di vided into 8 groups as normal group A, model group B, and treatment group C, D, E, F, G and H. Gerbil in groups B, C, D, E, F, G and H were infected with 120~ 2 cercariae of Schistosoma japonicum. Then on day 0 and day 21, three different doses of CsA (10, 20, and 50 mg/kg ~ d ) were given to the gerbil in group C, D, E, F, G, and I4 for 5 consecutive days. All ger bils were killed after 5 weeks. Adult worms were collected and counted and the worm reduction rate was calculated. Scanning electron microscopy (SEM) and transmission electron microscope (TEM) were used to observe the damage of the body surface. The sizes of egg granuloma and degrees of liver fibrosis were observed dynamically by HE staining and Masson staining respec- tively. According to the experimental results, all the infected gerbils have egg granulomas in different sizes. After CsA treat ment, the size of egg granulomas was reduced more or less, especially in high dose group. HE staining showed that compared with the model group, the granuloma areas did not change significantly in the low dose group. The higher the CsA dose was, the less the eggs and the more the reduction of granuloma size. Masson staining also showed that as the dose was increasing, the degree of liver fibrosis was gradually reducing. By application of SEM, we observed that the structures of worm surface, including spine and sensory, were regular in groups without drug treatment. However, worms' surface showed damages, visi- ble epidermal shrinkage and uneven variance in the low dose group. And the worm epidermis had ulceration with a large area break off in the high dose group. Besides, we also found the production of large number of vacuoles and the a disorder of cclJs structures by TEM observation.

关 键 词:环孢素A 日本血吸虫 肝纤维化 电镜 

分 类 号:R383.2[医药卫生—医学寄生虫学]

 

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