脑血管重构的发生发展与胞内Ca2+信号紊乱密切相关，但分子机理不清楚。有研究发现Ca2+通透阳离子通道TRPC6参与了肺动脉高压血管重构。我们预实验发现，在高血压大鼠模型上，脑动脉上TRPC3通道mRNA与蛋白表达量均显著上升，在体特异性阻断TRPC3 8周后血管重构改善明显。结果强烈提示TRPC3在高血压脑血管重构中发挥了重要作用。在培养脑动脉平滑肌上，预实验进一步发现，TRPC3开放激活金属蛋白酶ADAM17。鉴于ADAM17在EGFR受体转激活过程中的关键作用以及EGFR激活促进血管重构，我们因此假设TRPC3-Ca2+-ADAM17-EGFR是高血压脑血管重构中的重要通路。本研究拟在易卒中双肾双夹高血压大鼠模型上，特异性阻断TRPC3-ADAM17-EGFR通路后观察脑血管重构的改善，并结合离体细胞实验以加深机理认识。本研究将评估TRPC3是否为防治高血压脑血管重构的新靶点。

The pathogenesis of cerebrovascular remodeling in the context of hypertension is intimately associated with aberrant intracellular Ca2+ signaling in vascular smooth muscle cells (VSMCs), but how dysregulated Ca2+ signaling leads to VSMC dysfunction remains to be elucidated. TRPCs（Transient Receptor Potential Canonical）are Ca2+-permeable nonslective cation channels and TRPC6 has been implicated in vascular remodeling associated with pulmonary aterial hypertension. Our preliminary data showed that Ca2+-permeable TRPC3 channels were upregulated at mRNA and protein levels in hypertensive rats at 8 weeks post 2-kidney-2-clip operation, and that administration of TRPC3-specific channel blocker Pyr3 to hypertensive animals for 8 weeks significantly ameliorated cerebrovascular remodeling. These results therefore strongly suggested that TRPC3 channels via Ca2+ signaling would play an important role in cerebrovascular remodeling in the setting of hypertension. Further experiment in cultured cerebral VSMCs preliminarily showed that TRPC3 channel opening activated a membrane-bound metalloproteinase ADAM17 (a disintegrin and metalloproteinase 17). In light of the central role of ADAM17 in the transactivation of EGFR (Epidermal Growth Factor Receptor) signaling that is critical for VSMC hypertrophy, we hypothesized that TRPC3-Ca2+-ADAM17-EGFR represents an important signaling pathway involved in hypertension-induced cerebrovascular remodeling. The present study will establish the pathway in 2-kidney-2-clip stroke-prone hypertensive rats by employing specific blockers against each signaling molecules and perform in vitro experiment to dissect the detailed mechanisms. The results will further our understanding of cerebrovascular remodeling and provide evidence that may validate TRPC3 channels as a therapeutic target in the treatment of hypertension-associated complications such as cerebrovascular remodeling and stroke.