中国寄生虫学与寄生虫病杂志 ›› 2020, Vol. 38 ›› Issue (6): 688-694.doi: 10.12140/j.issn.1000-7423.2020.06.003

• 论著 • 上一篇    下一篇

藏药黄花香薷联合阿苯达唑治疗大鼠继发性多房棘球蚴感染的疗效研究

朱吉海1(), 曹得萍2, 切羊让中2, 刘珺2, 赵珺2, 刘燕2,*()   

  1. 1 青海大学附属医院心脏血管外科,西宁 810001
    2 青海大学医学院基础医学部,西宁 810001
  • 收稿日期:2020-07-27 出版日期:2020-12-30 发布日期:2021-01-12
  • 通讯作者: 刘燕
  • 作者简介:朱吉海(1983-),男,硕士,副主任医师,从事胸心外科疾病临床及基础研究。E-mail: zhujihai@126.com
  • 基金资助:
    国家自然科学基金(81960451);青海省科技厅自然科学基金(2017-ZJ-735);青海大学中青年科研基金(2016-QYY-5)

Effect of Elsholtzia eriostachya in combination with albendazole in treatment of secondary Echinococcus multilocularis metacestode infection in rats

ZHU Ji-hai1(), CAO De-ping2, QIE Yangrangzhong2, LIU Jun2, ZHAO Jun2, LIU Yan2,*()   

  1. 1 Department of Cardiovascular Surgery, Affiliated Hospital of Qinghai University, Xining 810001, China
    2 Department of Basic Medical Sciences, Medical College, Qinghai University, Xining 810001, China
  • Received:2020-07-27 Online:2020-12-30 Published:2021-01-12
  • Contact: LIU Yan
  • Supported by:
    National Natural Science Foundation of China(81960451);Natural Science Foundation of Qinghai Province Science and Technology Department(2017-ZJ-735);Qinghai University Youth Research Fund(2016-QYY-5)

摘要:

目的 观察藏药黄花香薷和阿苯达唑单用及联用治疗大鼠继发性原位多房棘球蚴感染的疗效,探讨藏药联合西药治疗多房棘球蚴感染的新途径。 方法 SD雄性大鼠开腹暴露肝脏,注入棘球蚴原头节混悬液0.2 ml(含2 × 103个原头节),建立大鼠继发性多房棘球蚴感染模型。40只感染模型大鼠随机均分为50 mg/(kg·d)阿苯达唑组、50 mg/(kg·d)黄花香薷组、25 mg/(kg·d)阿苯达唑 + 25 mg/(kg·d)黄花香薷联合用药组和感染对照组,另取10只健康SD大鼠为健康对照组。3个用药组大鼠每天灌胃给药1次,4周为1疗程,间隔5 d,共2个疗程;感染对照组和健康对照组小鼠均给予等体积生理盐水。治疗2个疗程后,各组大鼠称重,取肝脏测量病灶直径大小;取脾脏称重,计算脾脏指数;取肝脏和脾脏病灶组织,切片后行HE染色,于光学显微镜下观察组织病理变化,肝脏病灶组织另于透射电镜下进行超微结构观察。 结果 阿苯达唑组、黄花香薷组和联合用药组大鼠肝脏病灶直径分别为(0.72 ± 0.06)、(0.79 ± 0.10)、(0.62 ± 0.05)cm,均小于感染对照组的(1.10 ± 0.11)cm(P < 0.01),联合用药组的病灶直径小于阿苯达唑组和黄花香薷组,差异有统计学意义(P < 0.01)。联合用药组脾脏指数为5.28 ± 0.59,大于阿苯达唑组(3.35 ± 0.43)和黄花香薷组(3.56 ± 0.40)(P < 0.01)。HE染色观察结果显示,感染组和3个用药组的大鼠脾脏组织中白髓增殖明显,可见大量异形巨核细胞;3个用药组大鼠肝脏病灶组织均显示囊壁塌陷,其内原头节显著减少。黄花香薷组可见明显淋巴细胞浸润,联合用药组病灶组织坏死和玻璃样变明显。肝脏病灶组织超微结构观察显示,黄花香薷和阿苯达唑单用及联用治疗均能导致多房棘球蚴生发膜细胞线粒体结构破坏;联合治疗组肝棘球蚴囊壁结构疏松,生发层皮层区微绒毛变粗变短或者消失;黄花香薷组嗜酸粒细胞和巨噬细胞增加明显。 结论 黄花香薷和阿苯达唑联合治疗大鼠继发性多房棘球蚴感染有良好的效果。

关键词: 多房棘球蚴感染, 藏药, 黄花香薷

Abstract:

Objective To investigate the efficacy of the Tibetan medicine Elsholtzia eriostachya and albendazole, either alone or in combination, in treatment of secondary Echinococcus multiulocularis metacestode in rats, and to explore a new approach for treatment of the metacestode infection with Tibetan medicine combined with western medicine. Methods The SD male rats were laparotomized to expose the liver for injection with 0.2 ml of protoscoleces suspension (containing 2 × 103 protoscoleces) to establish the rat model of secondary E. multiulocularis metacestode infection. The 40 model rats were divided into the albendazole treatment group [50 mg/(kg·d)], Elsholtzia eriostachya treatment group [50 mg/(kg·d)], albendazole [25 mg/(kg·d)]+Elsholtzia eriostachya [25 mg/(kg·d)] group, and the infection control group. Another 10 healthy SD rats were used as the healthy control group. Rats in the 3 treatment groups received two courses of treatment by gavage with once daily for consecutive 4 weeks, at an interval of 5 days between courses. Rats in the infection control group and healthy control group were given an equal volume of normal saline. After two courses of treatment, the rats body were weighed, the liver lesion diameter was measured, and the spleen index was calculated. The liver and spleen tissues in each group were obtained and sectioned for HE staining. Histopathological changes were observed under optical microscope and the ultrastructure of liver lesions was further observed under a transmission electron microscope. Results The diameters of rat liver lesions in the albendazole group, Elsholtzia eriostachya group and the combination group were (0.72 ± 0.06) cm, (0.79 ± 0.10) cm, and (0.62 ± 0.05) cm, respectively, all of which were smaller than the (1.10 ± 0.11) cm of the control group (P < 0.01). The diameter of the lesion in the combination group was significantly smaller than that of the albendazole group and the Elsholtzia eriostachya group (P < 0.01). The spleen index of the combined medication group was 5.28 ± 0.59, which was significantly higher than that of the albendazole group (3.35 ± 0.43) and the Elsholtzia eriostachya group (3.56 ± 0.40) (P < 0.01). Furthermore, the HE staining revealed obvious proliferation of white marrow in rat spleen tissues in the infection group and the three treatment groups, with the presence of a large number of heteromorphic megakaryocytes. The liver lesions in three treatment groups all showed collapse of the cyst wall and significant reduction of protoscoleces. Obvious lymphocyte infiltration was seen in the Elsholtzia eriostachya group, and necrosis and hyaline degeneration were obvious in the combined treatment group. Ultrastructural observations of liver tissues showed that treatment with Elsholtzia eriostachya and albendazole alone or in combination lead to the destruction of the mitochondrial structure of the germinal membrane cells of the metacestode. In the combination treatment group, the metacestode showed loose wall structure, and the microvilli of the germinal cortex became thicker, shorter or even disappeared,. eosinophils and macrophages increased significantly in the Elsholtzia eriostachya group. Conclusion The treatment with combination of Elsholtzia eriostachya and albendazole presented a good therapeutic effect on secondary E. multiulocularis metacestode infection in rats.

Key words: Echinococcus multilocularis protoscoleces infection, Tibetan medicine, Elsholtzia eriostachya

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