Chongqing Key Laboratory of Biochemistry & Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, People's Republic of China.
Department of Neurosurgery, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, People's Republic of China.
Neurochem Res. 2020 Aug;45(8):1758-1768. doi: 10.1007/s11064-020-03037-8. Epub 2020 May 22.
This study was conducted to prepare β-caryophyllene loaded liposomes (BCP-LP) and investigated their effects on neurovascular unit (NVU) damage after subarachnoid hemorrhage (SAH) in rats. A blood injection into the pre-chiasmatic cistern was used to achieve SAH. BCP-LP were prepared, characterized and administrated to rats with SAH. The prepared BCP-LP were spherical with a size distribution of approximately 189.3 nm and Zeta potential of - 13.9 mV. Neurological scoring, the balance beam test, cerebral blood flow monitoring, brain edema and biochemical analyses were applied to evaluate the effects of BCP-LP on rat NVU damage after SAH. The results demonstrated that BCP-LP treatment improved neurological function disorder, balance ability and cerebral blood perfusion in rats. Brain edema detection and blood-brain barrier permeability detection revealed that BCP-LP could reduce brain edema and promote repairment of blood-brain barrier after SAH. Using the western blot experiments, we demonstrated that BCP-LP attenuated the loss of tight junction proteins Occludin and Zonula occludens-1, inhibit the high expression of VEGFR-2 and GFAP, and promote the repair of laminin. These results demonstrate the protective effect BCP-LP exert in the NVU after SAH in rats, and supports the use of BCP-LP for future study and therapy of SAH.
本研究旨在制备β-石竹烯负载脂质体(BCP-LP),并研究其对大鼠蛛网膜下腔出血(SAH)后神经血管单元(NVU)损伤的影响。通过向视交叉前池内注射血液来实现 SAH。制备、表征并给予 SAH 大鼠 BCP-LP。所制备的 BCP-LP 呈球形,粒径分布约为 189.3nm,Zeta 电位为-13.9mV。神经功能评分、平衡木试验、脑血流监测、脑水肿和生化分析用于评估 BCP-LP 对 SAH 后大鼠 NVU 损伤的影响。结果表明,BCP-LP 治疗可改善大鼠的神经功能障碍、平衡能力和脑血流灌注。脑水肿检测和血脑屏障通透性检测表明,BCP-LP 可减轻脑水肿并促进 SAH 后血脑屏障的修复。通过 Western blot 实验,我们证明 BCP-LP 可减轻紧密连接蛋白 Occludin 和 Zonula occludens-1 的丢失,抑制 VEGFR-2 和 GFAP 的高表达,并促进层粘连蛋白的修复。这些结果表明 BCP-LP 在大鼠 SAH 后 NVU 中发挥保护作用,支持将 BCP-LP 用于未来的 SAH 研究和治疗。