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目的:观察不同剂量低分子肝素钠对急性DVT大鼠在不同时期治疗后血管形态学的变化。方法:将72只SD大鼠制备模型后,随机按血栓形成后1、3、7、14d分期,每期18只,分为Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期。然后每期再根据低分子肝素钠剂量分为:低分子肝素钠小剂量组(700U/kg、一次/24h,n=6)、低分子肝素钠大剂量组(700U/kg、二次/24h,n=6)、模型组(0U/kg,n=6)。低分子肝素钠大、小剂量组均由大鼠腹壁皮下注射,连续7日。实验结束后获取病变段血管,观察内皮细胞数量变化,胶原阳性染色面积百分比变化,并与同期模型组进行比较。结果:模型组在Ⅱ期、Ⅲ期分别死亡一只,低分子肝素钠治疗大剂量组Ⅰ期、Ⅲ期、Ⅳ期内死亡4只。在Ⅰ期低分子肝素钠大、小剂量组内皮细胞数量与模型组相比均有统计学差异(P<0.05),组间亦有差异.低分子肝素钠大、小剂量组胶原阳性染色面积百分比与模型组相比均有统计学差异(P<0.05),组间相比无差异;在Ⅱ期,低分子肝素钠大、小剂量组内皮细胞数量与模型组相比均有统计学差异(P<0.05),组间无差异;在Ⅲ期、Ⅳ期低分子肝素钠大、小剂量组内皮细胞数量与模型组相比无统计学差异(P>0.05);在Ⅱ期、Ⅲ期低分子肝素钠大、小剂量组胶原阳性染色面积百分比与模型组相比仍有统计学差异(P<0.05),组间亦有差异;在Ⅳ期低分子肝素钠大、小剂量组胶原阳性染色面积百分比与模型组相比无统计学差异(P>0.05)。结论:血栓形成3d内,大、小剂量低分子肝素钠对内皮细胞均有保护作用,以大剂量效果较好。血栓形成7d内,大、小剂量低分子肝素钠对对胶原增生均有抑制作用,随着时间的延长,以大剂量低分子肝素钠抑制作用最强。
Objective: To observe the changes of vascular morphology after different doses of low molecular weight heparin in acute DVT rats. Methods: Seventy-two Sprague-Dawley rats were randomly divided into three groups: stage Ⅰ, stage Ⅱ, stage Ⅲ, and stage Ⅳ. Then each period was divided into low molecular weight heparin sodium dose (700U / kg, once / 24h, n = 6), low molecular weight heparin sodium dose group (700U / kg, twice / 24h , n = 6), model group (0U / kg, n = 6). Low molecular weight heparin sodium, small dose group were subcutaneously injected by the abdominal wall of rats for 7 days. At the end of the experiment, the blood vessels of diseased segments were obtained. The changes of the number of endothelial cells and the percentages of collagen-positive staining area were observed and compared with the model group at the same period. Results: In the model group, one died in stage Ⅱ and Ⅲ, and 4 died in stage Ⅰ, Ⅲ, Ⅳ of low molecular weight heparin treatment group. There was a significant difference in the number of endothelial cells between low and high dose heparin sodium group and model group (P <0.05), there were also differences between the two groups.Low molecular weight heparin sodium large and small dose group collagen positive staining area There was no significant difference between the two groups (P <0.05). In the second phase, the number of endothelial cells in low and high molecular weight heparin group was significantly lower than that in model group (P <0.05). There was no significant difference between the two groups (P> 0.05). There was no significant difference in the number of endothelial cells between the low and high dose heparin sodium groups in stage Ⅲ and Ⅳ compared with the model group (P> 0.05) Low-molecular-weight heparin sodium large and small doses of collagen positive staining area percentage compared with the model group is still statistically significant (P <0.05), also differences between groups; Ⅳ low molecular weight heparin sodium large and small doses of collagen positive There was no significant difference in staining area percentage between the model group and the model group (P> 0.05). Conclusion: Within three days after thrombosis, large and small doses of low molecular weight heparin have a protective effect on endothelial cells, which is effective in large doses. Within 7 days of thrombosis, large and small doses of low molecular weight heparin inhibited collagen hyperplasia. With the prolongation of time, high-dose and low molecular weight heparin sodium showed the strongest inhibitory effect.