高血压时TRPC3激活致单核细胞线粒体功能障碍的机制

高血压时单核细胞介导的氧化应激(ROS)是动脉粥样病变的始动环节，瞬时受体电位通道3（TRPC3）激活与单核细胞活化有关。但尚不清楚TRPC3激活是否调控线粒体钙致ROS生成增加。研究报道TRPC激活能促进线粒体膜通透性转移孔(mPTP)开放, ROS生成增加。我们前期研究发现高血压时单核细胞TRPC3激活介导钙内流增加促进单核细胞迁移，与收缩压及炎症因子增加有关。为此，我们提出高血压时单核细胞TRPC3激活介导细胞内Ca2+增加，通过调控Bcl-2、HKs和Akt信号通路，导致线粒体钙增加，mPTP开放异常ROS生成增加，促进高血压发展为动脉粥样硬化的假说。本研究拟以遗传性高血压大鼠为研究对象，阐明高血压时TRPC3激活介导单核细胞线粒体钙增加致mPTP开放异常的机制，探讨血管紧张素II受体阻断剂能否通过调控线粒体HKs对抗ROS生成的作用，研究对高血压动脉粥样病变的防治有重要意义。

Reactive Oxidative stress (ROS) mediated by monocytes in hypertension is the initial step of atherosclerotic lesions, transient receptor potential channel canonical type (TRPC3) activation was associated with activation of monocyte. But it is not clear if the TRPC3 activation mediated by increased intracellular calcium would lead to increased production of ROS. Other studies have found that TRPC activation can promote the mitochondrial membrane permeability transition pore (mPTP) opening, increasing production of ROS.Our study shown that increased migration of monocytes in essential hypertension is associated with increased TRPC3, which related to increased systolic blood pressure and inflammatory factor. We hypothesis that increased TRPC3 mediated by activation of Ca2+ influx increased, through the regulation of Bcl-2, HKs and Akt signal pathway, leading to increased mitochondrial calcium, make mPTP open abnormal, increased generation of ROS, promote the development of atherosclerosis in hypertension. This study intends to genetically hypertensive rats as objects, make sure that how to mediate monocyte increased mitochondrial calcium induced mechanism of mPTP open abnormal when TRPC3 activation in hypertension, angiotensin II receptor blockers regulation of mitochondrial HKs against the ROS role. It has important significance for prevention and treatment of atherosclerosis in hypertension.