缺血性脑损伤星形胶质细胞HSP70表达对神经元的保护效应研究

It is well known that heat shock protein 70 (HSP70) protects neurons in conditions of ischemia injury, and lower amount of HSP70 may be linked to enhanced neuronal susceptibility. Recent reports show that glia could release HSP70, and the heat stress tolerance of neuronal cells are increased by taking up HSP70. HSP70 expression also increases in astrocytes, which protects neurons in conditions of ischemia reperfusion. Howerver, the mechanism of the increased HSP70 expression in astrocytes, and whether HSP70 is a kind of link bridge between astroctyes and neurons against ischemia reperfusion remain unclear. In this study, using primary cultured astroctyes, astroctyes-neurons co-culture system and focal cerebral ischemia reperfusion models, we aim to examin that ischemia reperfusion may increase HSP70 expression and release through the activation of extracellular signal regulated kinase 1 and 2(ERK1/2) and phosphatidylinositol-3 kinase( PI3K)/Akt signaling pathways in astroctyes; HSP70 taken up by neurons not only increase neuronal HSP70 level directly, but promote intrinsic HSP70 synthesis, thus increasing neuronal tolerance to ischemia reperfusion injury. The study is to explore the mechanism of astrocytes protect neurons in ischemic cerebrovascular disease, and provide insights to the development of new therapeutic strategies by regulating the astrocytes function to protect neurons.

热休克蛋白70 （HSP70）对缺血损伤神经元的保护已得到公认，HSP70的含量成为神经元易感性的指标。近来发现胶质细胞能释放HSP70，神经元摄取HSP70可抵御热应激损伤。在脑缺血时海马星形胶质细胞（AS）HSP70表达增加，对神经元有保护作用，但HSP70增加的机制及HSP70是否是AS保护神经元抵御缺血损伤的桥梁目前是研究的空白。本研究拟在原代星形胶质细胞、神经元-星形胶质细胞共培养体系、局灶脑缺血再灌注模型上证实：AS在缺血再灌注下通过激活ERK1/2与PI3K/Akt增加HSP70的表达与释放；AS释放的HSP70被神经元摄取，一方面直接增加神经元HSP70水平，另一方面促进神经元内源性HSP70的合成，增强神经元对缺血损伤的耐受。本项目使我们认识了缺血性脑血管病AS对神经元的保护机制，还为调控AS的功能使其向保护神经元的方向发展开辟了新的治疗方向。

热休克蛋白70 （HSP70）对缺血损伤神经元的保护已得到公认，HSP70的含量成为神经元易感性的指标。近来发现胶质细胞能释放HSP70，神经元摄取HSP70可抵御热应激损伤。在脑缺血时海马星形胶质细胞（AS）HSP70表达增加，对神经元有保护作用，但HSP70增加的机制及HSP70是否是AS保护神经元抵御缺血损伤的桥梁目前是研究的空白。本研究在原代星形胶质细胞、神经元-星形胶质细胞共培养体系证实了：沉默星形胶质细胞HSP70 的表达后，其HSP70的表达及释放量的明显减少，神经元内PI3K/AKT、ERK 1/2通路蛋白表达的明显降低，同时神经元细胞活性明显降低，提示AS释放及被神经元摄取的HSP70减少，降低了神经元内的HSP70水平及其表达。本项目使我们认识了缺血性脑血管病AS对神经元的保护机制，还为调控AS的功能使其向保护神经元的方向发展开辟了新的治疗方向。