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大鼠下腔静脉(ICV)结扎术和稳定型胃十五肽 BPC 157 的新见解。

Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157.

机构信息

Departments of Pharmacology, University of Zagreb, Zagreb, Croatia.

Departments of Pharmacology, University of Zagreb, Zagreb, Croatia.

出版信息

Vascul Pharmacol. 2018 Jul;106:54-66. doi: 10.1016/j.vph.2018.02.010. Epub 2018 Mar 3.

Abstract

UNLABELLED

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome.

METHODS

We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression.

RESULTS

Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged.

CONCLUSION

As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.

摘要

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大鼠下腔静脉(ICV)结扎(至右卵巢静脉(ROV))通常代表了 Virchow 的重现:结扎导致血管损伤、停滞、血栓形成和血液动力学变化。我们发现 BPC 157 的治疗共同减弱或对抗了所有这些事件和整个综合征。

方法

我们应用 BPC 157(10μg,10ng/kg)作为早期方案或延迟治疗。评估包括微血管相机的大体评估;显微镜、静脉造影、出血、血压、心电图、热成像、血浆和 ICV 中的 MDA 和 NO 水平,以及基因表达。

结果

直接静脉损伤、血栓形成、血小板减少、出血延长均被对抗。此外,还显示了迅速出现的侧支循环和原本被困住的血液量的重新分布(通过左卵巢静脉(LOV)和其他静脉绕过),同时伴有静脉高压、动脉低血压和心动过速的对抗。BPC 157 大鼠的血浆 NO 值升高,但 MDA 值正常;在 ICV 组织中,NO 值恢复正常,MDA 水平降低。ICV、ROV 和 LOV 中 EGR、NOS、SRF、VEGFR 和 KRAS 的表达改变显示出水平的增加或减少,而一些基因则持续不变。

结论

作为一个新的见解,BPC 157 的应用大大减弱了甚至完全消除了大鼠 ICV 结扎的所有后果。

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