背景：TRPC6通道蛋白在心血管系统分布广泛，通道功能或表达的改变与多种血管疾病有关，包括动脉粥样硬化。前期的研究结果表明轻度重复性创伤性脑损伤使血管的内皮功能受损，而这一过程与TRPC6的激活有关。而AS发生与血管内皮功能损伤密切相关，因此mTBI加速AS可能与内皮TRPC6通道相关。
目的：研究重复性的轻度TBI介导的TRPC6通道表达与功能的改变对小鼠动脉粥样硬化病变的影响。
方法：将15周左右的雄性ApoE^-/-小鼠，分为mTBI和sham两组，每组12只，建立ApoE^-/-背景下的TRPC6-KO小鼠，同样分为mTBI和sham两组，每组12只，每隔72小时对TBI组实验小鼠进行颅脑打击，诱发轻度TBI，共三次。十周后收集模型小鼠的心脏、主动脉血管，通过Red Oil O染色、 Masson’s trichrome、Evans blue染色和免疫组化(特异性a- actin、VCAM-1、Mac-3和TRPC6染色)，对rmTBI组和sham组动脉粥样硬化斑块的面积和细胞成分进行分析。使用等张张力测试系统对主动脉血管的张力和内皮舒张功能进行测试。
结论：ApoE^-/-小鼠mTBI组的动脉粥样硬化斑块面积明显大于sham组，说明重复轻度ApoE^-/-背景下的TRPC6敲除小鼠的内皮功能与ApoE^-/-小鼠相比得到一定的改善，明确了rmTBI促进AS与TRPC6通道表达或功能有关。该通道有可能成为治疗和预防mTBI患者后期动脉粥样硬化的一个新靶点。
Background:TRPC6 channel proteins are widely distributed in the cardiovascular system, and alterations in channel function or expression are associated with a variety of vascular diseases, including atherosclerosis. Previous studies have shown that mild repetitive traumatic brain injury impairs vascular endothelial function, and this process is associated with the activation of TRPC6. The occurrence of AS is closely related to vascular endothelial function injury, so mTBI acceleration of AS may be related to endothelial TRPC6 channels.
Objective: To investigate the effects of repetitive mild TBI mediated changes in TRPC6 channel expression and function on atherosclerotic lesions in mice.
Methods: Male ApoE^-/- mice of about 15 weeks were divided into mTBI and sham groups, with 12 mice in each group. TRPC6-KO mice under the ApoE^-/- background were also divided into mTBI and sham groups, with 12 mice in each group. The mice in the TBI group were subjected to craniocerebral shock every 72 hours to induce mild TBI, a total of three times. After 10 weeks, the blood vessels of heart and aorta of model mice were collected and stained by Red Oil O, Masson's Trichrome, Evans Blue, and immunohistochemistry (specific a-actin, VCAM-1, MAC-3, and TRPC6 staining). The area and cell composition of atherosclerotic plaques in the RMTBI group and the Sham group were analyzed. Aortic vascular tension and endothelial diastolic function were measured using an isotonic tension test system.
Results: The area of atherosclous plaque in ApoE^-/- mice mTBI group was significantly larger than that in Sham group, indicating that the endothelial function of TRPC6 knockout mice under repeated mild ApoE^-/- background was improved compared with that of ApoE^-/- mice, confirming that rmTBI promotion of AS is related to the expression or function of TRPC6 channel. This channel may be a new target for the treatment and prevention of late atherosclerosis in patients with mTBI.
 

TRPC6 channel; Atherosclerosis; Traumatic brain injury; Knockout mice