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血小板 P2Y 抑制剂对小鼠后肢缺血诱导血管生成的抗血管生成作用。

Antiangiogenic Effect of Platelet P2Y Inhibitor in Ischemia-Induced Angiogenesis in Mice Hindlimb.

机构信息

School of Medicine, Jiangsu University, Zhenjiang 212013, China.

Clinical Laboratory, Huai'an Second People's Hospital Affiliated to Xuzhou Medical University, Huai'an 223002, China.

出版信息

Biomed Res Int. 2021 Apr 8;2021:5529431. doi: 10.1155/2021/5529431. eCollection 2021.

Abstract

PURPOSE

Postischemic inflammation induces angiogenesis, while platelet P2Y inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia.

METHODS

Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production.

RESULTS

Ischemic hindlimb angiogenesis was sharply decreased in IL-10 mice than IL-10 mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10 mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10) C57BL/6J mice.

CONCLUSION

The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.

摘要

目的

缺血后炎症诱导血管生成,而血小板 P2Y 抑制剂可减轻这种炎症。因此,我们研究了 P2Y 抑制剂替格瑞洛在小鼠后肢缺血模型中对血管生成的潜在作用。

方法

激光多普勒灌注成像和毛细血管密度测量用于量化血管生成。免疫荧光用于检测 CD31 水平。采集小鼠肌肉进行酶联免疫吸附(ELISA)测定白细胞介素(IL)-10 活性和 Western blot 测定血管内皮生长因子(VEGF)的产生。

结果

与野生型(WT)小鼠相比,IL-10 基因敲除(IL-10)小鼠缺血后肢血管生成明显减少。替格瑞洛显著抑制血管生成和血液再灌注恢复,显著增加 IL-10 小鼠缺血后肢 IL-10 水平,并降低 VEGF 的表达,而在 IL-10 缺陷(IL-10)C57BL/6J 小鼠中则被消除。

结论

本研究强调了替格瑞洛抗血管生成功能的作用与更高的 IL-10 表达有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4b/8052144/e13898556096/BMRI2021-5529431.001.jpg

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