Vitamin D attenuates cerebral artery remodeling through VDR/AMPK/eNOS dimer phosphorylation pathway after subarachnoid hemorrhage in rats
Vitamin D attenuates cerebral artery remodeling through VDR/AMPK/eNOS dimer phosphorylation pathway after subarachnoid hemorrhage in rats
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DOI：
10.1177/0271678x17726287
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发表时间：
2019-02-01
影响因子：
6.3
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
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作者：
Enkhjargal, Budbazar;Malaguit, Jay;Zhang, John H.
探讨维生素D3(VitD3)在蛛网膜下腔出血(SAH)后脑动脉内皮细胞骨桥蛋白(OPN)和内皮型一氧化氮合酶(ENOS)上调中的作用。采用SD大鼠血管内穿孔SAH模型(n=103)。与幼鼠(n=5)相比，VitD3预处理(30 ng/kg)可增加脑动脉内源性OPN和eNOS的表达。SAH前+VitD3组神经行为评分较SAH组明显改善。在SAH前+VitD3+VDR siRNA和前SAH+VitD3+OPN siRNA大鼠(每组5只)侧脑室注射维生素D受体(VDR)siRNA和OPN，分别减弱VitD3的作用。SAH+VitD3大鼠脑动脉VDR、OPN显著增加，C44剪接减少，导致基底动脉管腔增大。VDR表达增加导致脑动脉内皮细胞AMPK和eNOS表达上调和磷酸化，尤其是二聚体形式。结果表明，VitD3可通过上调OPN和脑动脉Ser1177-二聚体上的AMPK(p-AMPK)和eNOS(p-eNOS)的磷酸化来减轻脑动脉重构和血管痉挛。维生素D可能是一种有效的预防和治疗中风患者脑动脉重构的新策略。
The role of vitamin D3 (VitD3) in the upregulation of osteopontin (OPN) and eNOS in the endothelium of cerebral arteries after subarachnoid hemorrhage (SAH) is investigated. The endovascular perforation SAH model in Sprague-Dawley rats (n = 103) was used. The VitD3 pretreatment (30 ng/kg) increased endogenous OPN and eNOS expression in cerebral arteries compared with naive rats (n = 5 per group). Neurobehavioral scores were significantly improved in Pre-SAH+VitD3 group compared with the SAH group. The effects of VitD3 were attenuated by intracerebroventricular (i.c.v) injections of siRNA for the vitamin D receptor (VDR) and OPN in Pre-SAH+VitD3+VDR siRNA and Pre-SAH+VitD3+OPN siRNA rats, respectively (n = 5 per group). The significant increase of VDR, OPN and decrease of C44 splicing in the cerebral arteries of Pre-SAH+VitD3 rats lead to an increase in basilar artery lumen. The increase in VDR expression led to an upregulation and phosphorylation of AMPK and eNOS, especially dimer form, in endothelium of cerebral artery. The results provide that VitD3 pretreatment attenuates cerebral artery remodeling and vasospasm through the upregulation of OPN and phosphorylation of AMPK (p-AMPK) and eNOS (p-eNOS) at Ser1177-Dimer in the cerebral arteries. Vitamin D may be a useful new preventive and therapeutic strategy against cerebral artery remodeling in stroke patients.