舒尼替尼与阿苯达唑联合用药对泡状棘球蚴治疗效果的实验研究  

Sunitinib in combination with albendazole for the treatment of alveolar echinococcosis

作　　者：杜云峰 姜慧娇 刘程豪 侯卜文 舒敏 黎广 陈雪玲[2] 吴向未[1,3] DU Yunfeng;JIANG Huijiao;LIU Chenghao;HOU Bowen;SHU Min;LI Guang;CHEN Xueling;WU Xiangwei(School of Medicine,Shihezi University/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases,Shihezi,Xinjiang 832000,China;Department of Immunization,School of Medicine,Shihezi University,Shihezi,Xinjiang 832000,China;Department of Hepatobiliary Surgery,The First Affiliated Hospital of Medical College,Shihezi University,Shihezi,Xinjiang 832000,China)

机构地区：[1]石河子大学医学院/国家卫生健康委中亚高发病防治重点实验室,新疆石河子832000 [2]石河子大学医学院免疫教研室,新疆石河子832000 [3]石河子大学医学院第一附属医院肝胆外科,新疆石河子832000

出　　处：《石河子大学学报（自然科学版）》2023年第5期599-607,共9页Journal of Shihezi University(Natural Science)

基　　金：国家自然基金项目(81760570);中国医学科学院中央级公益性科研院所基本科研业务费专项(2020-PT330-003);新疆生产建设兵团促进科技成果转化引导计划项目(2021BB006);新疆生产建设兵团中青年领军人才项目(2018CB017)。

摘　　要：目的体内外实验探讨舒尼替尼联合阿苯达唑抗泡状棘球蚴活性。方法体外对应药物浓度培养原头节后镜下观察其活性并计算成活率;腹腔感染泡状棘球蚴小鼠治疗60 d后,称量囊湿重并计算抑囊率。试剂盒检测AST、ALT、IL-2,IL-4水平。HE观察病理学改变,免疫组化检测CD4、CD34表达水平。结果体外培养第7 d ABZ+SU11248组原头节存活率(45.168%±3.903%)低于ABZ组(59.198%±1.894%)和SU11248组(69.232%±3.673%);ABZ+SU11248组的囊湿重(2.566±1.080)g低于ABZ组(4.519±0.4934)g,SU11248(5.384±0.6586)g组和Control组(10.25±1.979)g;ABZ+SU11248组抑囊率74.94%高于ABZ组55.91%和SU11248组47.47%;ABZ+SU11248组ALT、AST水平中低于其他给药组,IL-2、IL-4水平较其他给药组明显升高。ABZ+SU11248组原头节畸形改变,角质层变薄,生发层紊乱。ABZ+SU11248组免疫组化CD4评分(10.13±1.46)高于Control组(4.00±1.07)和ABZ组(6.50±3.34);CD34评分(1.88±1.25)低于Control组(6.38±1.85),ABZ组(6.63±1.69)和SU11248组(4.25±1.17)。结论舒尼替尼能够通过抑制血管新生来抑制泡状棘球蚴的生长,其与阿苯达唑联合治疗比二者单独治疗对泡状棘球蚴活性抑制作用更强且造成更低的肝损伤。Objective To investigate the anti-alveolar echinococcosis activity of sunitinib combined with albendazole in vitro and in vivo.Methods The activity was observed and the survival rate was calculated under the posterior microscope after cultured with the corre-sponding drug concentration in vitro.After 60 days of treatment,the wet weight of the cyst was measured and the rate of cyst inhibition was calculated.AST,ALT,IL-2 and IL-4 levels were detected by the kit.The pathological changes were observed by HE,and the expression levels of CD4 and CD34 were detected by immunohistochemistry.Results The survival rate of alveolar echinococcosis proto-scoleces in ABZ+SU11248 group(45.168%±3.903%)was lower than that in ABZ group(59.198%±1.894%)and SU11248 group(69.232%±3.673%)on the 7th day of culture in vitro.The wet weight of capsule in ABZ+SU11248 group(2.566±1.080)g was lower than that in ABZ group(4.519±0.4934)g,SU11248 group(5.384±0.6586)g and Control group(10.25±1.979)g.The rate of sac inhibition in ABZ+SU11248 group 74.94%was higher than that in ABZ+SU11248 group 55.91%and SU11248 group 47.47%.The levels of ALT and AST in ABZ+SU11248 group were lower than those in other administration groups,and the levels of IL-2 and IL-4 were significantly higher than those in other administration groups.ABZ+SU11248 group was characterized by malfor-mation,thinning of cuticle layer and disorder of germinal layer.Immunohistochemical CD4 score in ABZ+SU11248 group(10.13±1.46)was higher than that in Control group(4.00±1.07)and ABZ group(6.50±3.34).The score of CD34(1.88±1.25)was low-er than that of Control group(6.38±1.85),ABZ group(6.63±1.69)and SU11248 group(4.25±1.17).Conclusion Sunitinib can inhibit the growth of alveolar echinococcosis by inhibiting angiogenesis.The combination of Sunitinib and albendazole has a stronger in-hibitory effect on the activity of alveolar echinococcosis and causes less liver damage than the two treatments alone.

关 键 词：泡状棘球蚴 阿苯达唑 舒尼替尼 联合用药 

分 类 号：R532.32[医药卫生—内科学]