蛋白酶激活受体1和4信号抑制可减轻早产新生儿出血性脑损伤。
Protease-activated receptor 1 and 4 signal inhibition reduces preterm neonatal hemorrhagic brain injury.
作者信息
Lekic Tim, Klebe Damon, McBride Devin W, Manaenko Anatol, Rolland William B, Flores Jerry J, Altay Orhan, Tang Jiping, Zhang John H
机构信息
From the Departments of Physiology and Pharmacology (T.L., D.K., D.W.M., A.M., W.B.R., J.J.F., O.A., J.T., J.H.Z.), Neurology (T.L.), and Neurosurgery (J.H.Z.), Loma Linda University School of Medicine, CA.
出版信息
Stroke. 2015 Jun;46(6):1710-3. doi: 10.1161/STROKEAHA.114.007889. Epub 2015 Apr 30.
BACKGROUND AND PURPOSE
This study examines the role of thrombin's protease-activated receptor (PAR)-1, PAR-4 in mediating cyclooxygenase-2 and mammalian target of rapamycin after germinal matrix hemorrhage.
METHODS
Germinal matrix hemorrhage was induced by intraparenchymal infusion of bacterial collagenase into the right ganglionic eminence of P7 rat pups. Animals were treated with PAR-1, PAR-4, cyclooxygenase-2, or mammalian target of rapamycin inhibitors by 1 hour, and ≤5 days.
RESULTS
We found increased thrombin activity 6 to 24 hours after germinal matrix hemorrhage, and PAR-1, PAR-4, inhibition normalized cyclooxygenase-2, and mammalian target of rapamycin by 72 hours. Early treatment with NS398 or rapamycin substantially improved long-term outcomes in juvenile animals.
CONCLUSIONS
Suppressing early PAR signal transduction, and postnatal NS398 or rapamycin treatment, may help reduce germinal matrix hemorrhage severity in susceptible preterm infants.
背景与目的
本研究探讨凝血酶的蛋白酶激活受体（PAR）-1、PAR-4在生发基质出血后介导环氧合酶-2和雷帕霉素靶蛋白的作用。
方法
通过向P7大鼠幼崽右侧神经节隆起内脑实质注射细菌胶原酶诱导生发基质出血。在1小时内及≤5天内，用PAR-1、PAR-4、环氧合酶-2或雷帕霉素靶蛋白抑制剂对动物进行治疗。
结果
我们发现生发基质出血后6至24小时凝血酶活性增加，PAR-1、PAR-4抑制可使环氧合酶-2和雷帕霉素靶蛋白在72小时内恢复正常。用NS398或雷帕霉素早期治疗可显著改善幼年动物的长期预后。
结论
抑制早期PAR信号转导以及产后用NS398或雷帕霉素治疗，可能有助于降低易感早产儿生发基质出血的严重程度。
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