大鼠下肢静脉曲张动物模型的建立  

Establishment of a rat model of varicose veins of the lower limbs

作　　者：何志勇[1] 李竣[2] 王线 陈丹丹 全志文 戴加伟 黄先菊[2] HE Zhiyong;LI Jun;WANG Xian;CHEN Dandan;QUAN Zhiwen;DAI Jiawei;HUANG Xianju(Experimental Teaching and Engineering Training Center and Innovation and Entrepreneurship College,South-Central Minzu University,Wuhan 430074,China;School of Pharmaceutical Sciences,South-Central Minzu University,Wuhan 430074,China;Wuhan Runhe Biopharmaceutical Co.,Ltd,Wuhan 430040,China)

机构地区：[1]中南民族大学实验教学与工程训练中心,创新创业学院,武汉430074 [2]中南民族大学药学院,武汉430074 [3]武汉润禾生物医药有限公司,武汉430040

出　　处：《中国实验动物学报》2024年第12期1556-1564,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：湖北省重点研发计划(2024BCA002,2022BCA053)。

摘　　要：目的通过手术构建一种接近临床的大鼠下肢静脉曲张动物模型,为评价药物治疗提供理论支持。方法SD大鼠30只,雌雄各半,随机分为对照组和手术组。手术组采用改良的下肢静脉结扎手术对大鼠下肢静脉结扎(包括小隐静脉和股静脉),即小隐静脉合并股静脉完全结扎手术,形成血栓导致下肢深静脉内压持久升高,从而引起下肢静脉曲张症状。手术组大鼠手术后第6周,对大鼠静脉曲张进行评分,评选出造模成功大鼠,然后将造模成功大鼠随机分为模型组和迈之灵组。迈之灵组使用迈之灵62.5 mg/kg灌胃每日一次,对照组和模型组每日给予等体积生理盐水灌胃,连续20 d,给药前1 d、给药后7、14和20 d时分别对大鼠小腿部进行微距拍照、评分,给药结束后模型组和迈之灵组取手术侧下肢踝关节以上大隐静脉约1 cm长,对照组取相同侧下肢对应部位大隐静脉进行病理组织观察。组织包埋蜡块分成两份,一份用于苏木素-伊红(HE)染色和马松(Masson)染色,另一份用于免疫组化(immunohistochemistry,IHC)检查白细胞介素2(interleukin 2,IL-2)和金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinases,TIMP-1)检测。结果手术组22只大鼠,有20只造模成功,造模成功率为91%。根据大鼠下肢小腿静脉扩张、曲张和红肿表现,与对照组相比,模型组静脉曲张评分增加,具有显著性差异(P<0.01),给予治疗剂量的迈之灵后,与模型组相比,迈之灵组静脉曲张评分减少,具有显著性差异(P<0.01)。病理检查显示模型组可见明显的静脉曲张样改变,有轻度炎症;迈之灵组静脉曲张改变和炎症减轻。结论成功建立了一种下肢静脉曲张大鼠模型,为下肢静脉曲张疾病相关药物和治疗方法的研究提供了新的研究方法。ObjectiveTo construct an accurate clinical model of lower limb varicose veins in rats through surgery that provides theoretical support for evaluating drug therapy.Methods30 SD rats,15 males and 15 females,were randomly divided into a control group and surgical group.In the surgical group,the rats lower limb veins(including the small saphenous vein and femoral vein)were ligated via improved lower limb vein ligation,i.e.,the small saphenous vein was completely ligated with the femoral vein,and the thrombosis result ed in a lasting increase in the internal pressure of the deep veins of the lower limb,causing varicose symptoms.On the 6th week after surgery,the varicose veins of the rats in the surgical group were scored to select those that were successfully modeled.Then,the successfully modeled rats were randomly divided into a model group and Maizhiling group.Maizhiling 62.5 mg/kg was orally administered to the treatment group once a day,while the control and model group received an equal volume of physiological saline orally every day for 20 consecutive days.On the day before administration and 7 d,14 d and 20 d after administration,macro photography and scoring were performed on the lower limbs of the rats.After completion,an approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side was removed from the model group and Maizhiling group rats,while from the control group,the corresponding saphenous vein of the lower limb on the same side was removed.Pathological tissue observation was performed using HE staining,Masson staining,and immunohistochemical examination for interleukin-2(IL-2)and tissue inhibitor of metalloproteinases(TIMP-1).ResultsOf the 22 rats in the surgical group,20 were successfully modeled,with a success rate of 91%.According to the manifestations of venous dilation,varicose veins,and redness in the lower limbs of rats,the varicose vein score of the model group increased significantly compared with that of the control group(P<0.01).After the therapeutic d

关 键 词：下肢静脉曲张 动物模型 迈之灵 

分 类 号：Q95-33[生物学—动物学]