抗血小板治疗和下腔静脉血栓大鼠静脉管壁慢性炎症的关系

The Relationship between Antiplatelet Therapy and Chronic Inflammation of the Venous Wall in Rats with Inferior Vena Cava Thrombosis

摘要: 目的：通过建立大鼠下腔静脉血栓模型，并予氯吡格雷干预，探究其对静脉管壁血小板–单核细胞集合体水平及纤维化程度的影响。方法：将24只SD雄性大鼠随机分为假手术组、模型组、低剂量(10 mg/kg)干预组、高剂量(30 mg/kg)干预组，每组6只。对模型组和低、高剂量干预组建立下腔静脉血栓模型，造模成功后予以药物干预。假手术组和模型组予以生理盐水灌胃，低、高剂量干预组分别予以氯吡格雷10 mg/kg、30 mg/kg灌胃，每天1次，7天后取大鼠下腔静脉组织进行Masson染色、CD115免疫组化染色和CD41-CD115免疫荧光双染。结果：各组纤维化面积比例比较，差异有统计学意义(F = 132.0, P < 0.01)，各组CD115荧光强度表达差异有显著性(F = 314.7, P < 0.01)，各组CD41-CD115双阳率差异有显著性(F = 147.3, P < 0.01)；模型组纤维化面积比例、CD115荧光强度表达、CD41-CD115双阳率明显高于假手术组(P < 0.01)，氯吡格雷低、高剂量干预组三种指标水平均明显低于模型组(P < 0.01)，氯吡格雷高剂量干预组三种指标水平均明显低于低剂量干预组(P < 0.05)。结论：深静脉血栓环境下，大鼠下腔静脉管壁血小板–单核细胞集合体水平、单核巨噬细胞浸润程度、纤维化程度升高，抗血小板药物氯吡格雷可能降低炎症、缓解管壁纤维化。

Abstract: Objective: To establish a rat model of inferior vena cava thrombosis and intervene with clopidogrel to explore its effects on platelet monocyte aggregation levels and fibrosis degree in the venous wall. Method: 24 male SD rats were randomly divided into a sham surgery group, a model group, a low-dose (10 mg/kg) intervention group, and a high-dose (30 mg/kg) intervention group, with 6 rats in each group. Establish inferior vena cava thrombosis models for the model group and low-dose and high-dose intervention groups, and administer medication intervention after suc-cessful modeling. The sham surgery group and model group were given physiological saline by ga-vage, while the low-dose and high-dose intervention groups were given clopidogrel 10 mg/kg and 30 mg/kg respectively, once a day. After 7 days, the inferior vena cava tissue of rats was taken for Masson staining, CD115 immunohistochemistry staining, and CD41-CD115 immunofluorescence double staining. Result: The proportion of fibrotic area in each group was compared, and the dif-ference was statistically significant (F = 132.0, P < 0.01). There was a significant difference in the expression of CD115 fluorescence intensity in each group (F = 314.7, P < 0.01), and there was a sig-nificant difference in the double positive rate of CD41-CD115 in each group (F = 147.3, P < 0.01); the proportion of fibrosis area, CD115 fluorescence intensity expression, and CD41-CD115 double posi-tive rate in the model group were significantly higher than those in the sham surgery group (P < 0.01). The levels of three indicators in the low-dose and high-dose intervention groups of clopidogrel were significantly lower than those in the model group (P < 0.01), and the average levels of three indicators in the high-dose intervention group of clopidogrel were significantly lower than those in the low-dose intervention group (P < 0.05). Conclusion: In the environment of deep vein thrombosis, the levels of platelet monocyte aggregates, degree of monocyte-macrophage infiltration, and degree of fibrosis in the inferior vena cava wall of rats increase. The antiplatelet drug clopidogrel may reduce inflammation and alleviate wall fibrosis.