人个体化急性缺血再灌注损伤大脑保护与修复芯片研究

Individualized treatment of acute ischemic stroke (AIS) has a beneficial effect on the prognosis and prevention of stroke. However, the mechanism of individualized brain protection and injury repair for AIS has not yet been clear. It is urgent to establish an individualized cellular model in vitro for the investigation of human acute ischemia-reperfusion injury. The "Universal chip for neural system" which we independently designed and patented lays a foundation for the establishment of such model. In addition, our previous studies found that the angiotensin II type 2 receptor (AT2R) agonist, compound 21 (C21), attenuated the neurologic deficits after AIS in mice; other studies showed that single nucleotide polymorphisms (SNPs) of AT2R affected AT2R expression. Then we speculate that SNPs of AT2R may affect the drug sensitivity of AIS to C21. Therefore, we intend to establish an individualized cellular model for acute ischemia-reperfusion injury depending on AT2R SNPs, using the "Universal chip for neural system", and the drug sensitivity of different genotypes of AT2R SNPs to C21 will be investigated for testing the application ability of the new model. At the same time, we will lay an important foundation for accelerating the clinical application of C21.

急性缺血性脑卒中（AIS）的个体化治疗对卒中的转归和防控具有重要意义，但其个体化脑保护与损伤修复机制尚未明确，亟待创建个体化的人急性缺血-再灌注损伤体外细胞模型深入探讨。我们前期自主设计并申请专利的“通用神经系统芯片”为创建此类模型奠定了基础。除此之外，我们前期研究发现，血管紧张素II2型受体（AT2R）激动剂化合物21（C21）可以减轻小鼠AIS后的神经缺损症状；另有研究表明，AT2R的单核苷酸多态性（SNPs）可影响AT2R的表达，据此我们推测AT2R的SNPs可能会影响AIS对C21的药物敏感性。为此，我们拟利用“通用神经系统芯片”基于AT2R的SNPs建立人个体化急性缺血-再灌注损伤大脑保护与修复芯片模型，并通过检测分析不同AT2R的SNPs基因型对C21的药物敏感性及机制来检验新模型的应用能力，同时为加快推动C21的临床转化应用打下重要基础。

急性缺血性脑卒中（AIS）的个体化治疗对卒中的转归和防控具有重要意义，但其个体化脑保护与损伤修复机制尚未明确，亟待创建个体化的人急性缺血-再灌注损伤体外细胞模型深入探讨。我们利用微流控芯片技术，通过对氧糖剥夺复氧复糖条件的精准控制，在体外高度模拟体内病理微环境，并应用人源性神经母细胞，创新性地成功构建了脑急性缺血-再灌注损伤微流控芯片细胞模型。我们前期研究发现，血管紧张素II2型受体（AT2R）激动剂化合物21（C21）可以减轻小鼠AIS后的神经缺损症状。另有研究报道，三叶苷可以改善小鼠脑急性缺血-再灌注损伤。据此，我们利用自主构建的脑急性缺血-再灌注损伤微流控芯片细胞模型，通过对C21及三叶苷改善神经细胞急性缺血性-再灌注损伤的药物敏感性及相关氧化应激机制研究，验证了此医工交叉联合创新的微流控芯片细胞模型优秀的的基础应用能力，同时也为加快推动C21的临床转化应用打下重要基础。

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