大鼠下肢静脉曲张动物模型的建立
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中南民族大学

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] 湖北省重点研发计划(No.2022BCA053),湖北省科技创新人才及服务专项(国际科技合作类)(No.2022EHB053)


Establishment of an animal model of varicose veins of lower limbs in rats
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South-Central Minzu University

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Production Process Monitoring and Functional Product Development of Traditional Chinese Medicine Slices (BZY21012)

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    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治疗组:迈之灵62.5 mg/kg灌胃每日一次,对照组和模型组每日给等体积生理盐水灌胃,连续20天,给药前1天、给药7天、14天、20天分别对大鼠下肢小腿部进行微距拍照、评分,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,采用HE染色、Masson染色、免疫组化检查白细胞介素2( IL-2)和金属蛋白酶组织抑制因子( TIMP-1)进行病理组织观察。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。

    Abstract:

    Objective To construct a nearly clinical animal model of lower limb varicose veins in rats through surgery, providing theoretical support for evaluating drug therapy. Method 30 SD rats, half male and half female, were randomly divided into a control group and a surgical group. In the operation group, the rats' lower limb veins ( including small saphenous vein and femoral vein ) were ligated by the improved lower limb vein ligation operation, that is, the small saphenous vein was completely ligated with femoral vein, and thrombosis resulted in a lasting increase in the internal pressure of the deep veins of the lower limb, thus causing varicose symptoms of the lower limb. At the 6th week after surgery, the varicose veins of the rats in the surgical group were scored to select the rats that were successfully modeled.Then, the successfully modeled rats were randomly divided into a model group and a treatment group: Maizhiling 62.5 mg/kg was orally administered once a day, while the control group and model group received equal volume of physiological saline orally every day for 20 consecutive days. On the day before administration, 7 days, 14 days, and 20 days after administration, macro photography and scoring were performed on the lower limbs of rats. After completion, the model group and the Maizhiling group took approximately 1 cm long saphenous vein above the ankle joint of the lower limb on the surgical side, while the control group took the corresponding saphenous vein of the lower limb on the same side. 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). Result Out of 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, compared with the control group, the varicose vein score in the model group increased significantly (P<0.01). After administering the therapeutic dose of Maizhiling, the varicose vein score in the Maizhiling group decreased significantly compared with the model group (P<0.01).Pathological examination showed significant varicose vein like changes and mild inflammation in the model group; The Maizhiling group reduced varicose veins and inflammation. Conclusion A rat model of lower limb varicose veins has been successfully established, providing a new research method for the study of drugs and treatment methods related to lower limb varicose diseases.

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  • 收稿日期:2024-06-26
  • 最后修改日期:2024-08-02
  • 录用日期:2024-12-02
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