NLRP2在脑缺血损伤中的作用及机制
发布时间：2018-07-29 09:49
【摘要】：研究目的脑中风,是近年来世界上导致长期致残和死亡的主要原因,具有发病率高,死亡率高,致残率高和复发率高的特点。其中,相比于出血性脑中风,缺血性脑中风更常见,所占比例超过80%,是由于大脑动脉阻塞从而阻断血液流向大脑导致组织坏死。缺血性脑中风也就是脑缺血的病理生理过程是复杂的、广泛的,包括氧化应激,兴奋性氨基酸毒性作用,能量代谢障碍,细胞离子动态平衡的改变,细胞内钙水平增加,活性氧介导的毒性,炎症细胞因子介导的细胞毒性作用等。最近的研究结果表明先天免疫系统的炎症反应与脑缺血发病过程和进展密切相关。先天免疫系统是限制宿主不受损伤的第一道防线,细胞内和细胞外含有模式识别受体(PRRs),它们可以检测到急性损伤,从而启动炎症反应。核苷酸结合寡聚化结构域(NOD)——样受体(NLRs)是细胞内模式识别受体家族的一个成员,在炎症反应中发挥关键作用。在人类22类NLRs中14类包含热蛋白结构域并形成NLRP亚型(NLRPs)。在NLRPs家族中,一些成员如NLRP1,NLRP3,NLRP6等已经被深入研究,它们可以通过结合蛋白ASC招募pro-caspase-1,激活炎性小体,使无活性的pro-caspase-1激活为成熟的caspase-1,从而导致IL-1β和IL-18的产生和释放并引发炎症反应。最近一项研究表明体外培养的人类星形胶质细胞表达NLRP2炎性小体,而NLRP2在体内的分布和作用却很少研究,特别是在中枢神经系统。那么NLRP2是否在体内中枢神经系统中表达以及是否与脑缺血等神经系统疾病相关仍需进一步探讨。在本次实验研究中,通过建立在体大脑中动脉栓塞(MCAO)模型和培养细胞的糖氧剥夺(OGD)模型从体内和体外两方面来探究NLRP2在脑缺血中的作用及可能的机制。研究方法1 NLRP2在小鼠脑缺血后的表达变化1.1 C57BL/6野生型小鼠脑缺血模型的构建及神经学评分1.1.1选取小鼠并构建缺血模型选取雄性野生型C57BL/6实验小鼠,体重23g左右,建立大脑中动脉栓塞模型。颈部正中切口,切开皮肤,在显微镜下钝性分离出左侧颈总动脉,颈内动脉及颈外动脉,将尼龙线栓小心插入颈总动脉,当脑血流仪检测到血流突然下降时停止继续插入,并开始计时,12、24、48小时后处死小鼠取材。1.1.2通过神经学评分评价模型是否建立成功。1.2脑缺血后NLRP2在小鼠脑中的表达变化及分布1.2.1使用蛋白质免疫印迹法(western blot,WB)、Real-time PCR和免疫组织化学法(immunohistochemistry,IHC)检测在脑缺血后NLRP2的表达变化情况。1.2.2采用组织免疫荧光(immunofluorescence,IF)方法对NLRP2与小鼠大脑的不同细胞的标记物蛋白进行荧光双染检测NLRP2在脑中的分布。1.3体外模型的构建及NLRP2的检测体外培养原代星形胶质细胞,建立糖氧剥夺(Oxygen Glucose Deprivation,OGD)模型,分别进行OGD处理0.5、1、1.5、2h,使用蛋白质免疫印迹法(western blot,WB)、组织免疫荧光(immunofluorescence,IF)和 Real-time PCR 检测OGD后原代星形胶质细胞中NLRP2的表达变化。2 NLRP2在小鼠脑缺血损伤中的作用2.1注射腺相关病毒沉默小鼠脑内NLRP2基因利用脑立体定位注射技术将携带NLRP2沉默基因的腺相关病毒载体注射到神经系统的特定部位,以沉默这个部位的NLRP2基因。2.2注射空病毒与注射携带NLRP2沉默基因的小鼠大脑形态学损伤对比注射空病毒与注射携带NLRP2沉默基因的小鼠脑缺血后处理,对注射空病毒与注射携带NLRP2沉默基因的小鼠大脑进行TTC染色,并对其形态学损伤进行评分。2.3小鼠脑缺血模型中炎症因子的检测利用CBA、Real-time PCR方法检测注射空病毒与注射携带NLRP2沉默基因的小鼠大脑匀浆中促炎因子的含量。2.4 NLRP2对OGD诱导的原代星形胶质细胞凋亡的影响2.4.1对星形胶质细胞进行转染2.4.2星形胶质细胞的凋亡检测对转染si-NLRP2的星形胶质细胞进行OGD处理,Annexin V/PI染色后,使用流式细胞仪检测OGD处理条件下,原代星形胶质细胞凋亡的影响。3脑缺血损伤中NLRP2通路的调控作用WB检测小鼠脑缺血后NLRP2对小鼠大脑caspase-1、ASC、IL-1β等相关蛋白水平的影响。WB检测NLRP2对注射空病毒与注射携带NLRP2沉默基因的病毒小鼠大脑caspase-1、ASC、IL-1β等相关蛋白水平。WB检测转染空si-RNA和转染si-NLRP2的星形胶质细胞OGD处理后,NLRP2对caspase-1、p-p65、IL-1β等蛋白表达的影响。研究结果1小鼠脑缺血后NLRP2及其下游分子在脑内的表达及作用1.1 C57BL/6小鼠脑缺血模型的构建及神经学评分由于死亡或者是神经学评分小于2分,每组大约有l5%小鼠被剔除。1.2脑缺血后NLRP2在小鼠脑中的表达变化及分布1.2.1使用蛋白质免疫印迹法(western blot,WB)、Real-time PCR和免疫组织化学法(immunohistochemistry,IHC)检测脑缺血后NLRP2的表达变化,通过WB、Real-time PCR分析,我们发现NLRP2在脑缺血后表达明显升高,并且在24小时达到高峰,免疫组化结果也证明这一点。1.2.2通过免疫荧光染色得出,NLRP2主要表达于原代星形胶质细胞,在神经元中也有少量表达,在小胶质细胞中几乎没有表达。1.3体外模型的构建及NLRP2的检测体外培养原代星形胶质细胞,建立糖氧剥夺OGD模型,通过WB、Real-time PCR结果分析,我们发现OGD后NLRP2表达明显升高,并且在OGD1.5小时达到高峰,免疫荧光结果显示细胞OGD1.5小时后,NLRP2表达升高。2 NLRP2在小鼠脑缺血损伤中的作用2.1注射腺相关病毒沉默小鼠脑内NLRP2基因注射病毒4周后,OCT包埋小鼠大脑组织,冰冻切片于显微镜下观察病毒侵染范围,范围较大,覆盖了大脑中动脉所支配的区域。2.2注射空病毒与注射携带NLRP2沉默基因的病毒小鼠大脑形态学损伤对比TTC染色结果显示,注射NLRP2沉默基因脑缺血后,小鼠神经学评分明显降低,脑梗死面积也明显减少,。2.3小鼠脑缺血模型中炎症因子的检测对注射空病毒和注射NLRP2沉默基因的病毒的小鼠进行脑缺血处理,CBA、Real-time PCR结果显示注射病毒所引起的NLRP2表达下降可以减轻脑缺血所引起的IL-1β、IL-18、IL-6、TNF-α MCP-1等炎性因子表达升高。2.4 NLRP2对OGD诱导的原代星形胶质细胞凋亡的影响流式结果显示,对转染si-NLRP2的星形胶质细胞进行OGD处理,凋亡的星形胶质细胞明显减少。3脑缺血损伤中NLRP2通路的调控作用WB结果显示,小鼠脑缺血后,NLRP2、caspase-1、ASC、IL-1β等相关蛋白表达升高;注射携带NLRP2沉默基因的病毒小鼠,与注射空病毒的小鼠相比,NLRP2表达降低,而且注射携带NLRP2沉默基因的病毒小鼠所引起的NLRP2下降可以减轻脑缺血所引起的caspase-1、ASC、IL-1β等相关蛋白升高;培养原代星形胶质细胞,WB结果显示,转入siRNA-NLRP2星形胶质细胞NLRP2表达明显降低。转染siRNA-NLRP2的细胞所引起的NLRP2表达下降可以减轻OGD所引起的caspase-1,p-p65,IL-Iβ等相关蛋白表达升高。研究结论本实验首次证明了 NLRP2在脑缺血损伤中的表达变化,发现脑缺血损伤后NLRP2表达升高,进一步导致caspase-1、ASC、IL-1β等相关蛋白升高,而NLRP2的缺失可以使脑梗死面积减少,脑缺血损伤得到改善,对于脑缺血具有一定的防治作用。
[Abstract]:In recent years, cerebral apoplexy is the main cause of long-term disability and death in the world, characterized by high morbidity, high mortality, high disability and high recurrence rate. Among them, ischemic stroke is more common than hemorrhagic stroke, with a proportion of more than 80%, which is due to obstruction of the brain artery to block the flow of blood to the brain. The pathophysiological process of ischemic cerebral apoplexy is complex and extensive, including oxidative stress, toxic effects of excitatory amino acids, energy metabolism disorders, changes in dynamic balance of cell ions, increased intracellular calcium levels, active oxygen mediated toxicity, and cytotoxic effects mediated by inflammatory cytokines. Recent studies have shown that the inflammatory response of the innate immune system is closely related to the process and progress of cerebral ischemia. The innate immune system is the first line of defense to restrict the undamaged host, and the intracellular and extracellular domain of the pattern recognition receptor (PRRs) can detect acute damage and initiate the inflammatory reaction. The oligomeric domain (NOD) - like receptor (NLRs) is a member of the intracellular pattern recognition receptor family and plays a key role in the inflammatory response. In the 22 category of human NLRs, 14 types include the thermal protein domain and form a NLRP subtype (NLRPs). In the NLRPs family, some members, such as NLRP1, NLRP3, and NLRP6, have been deeply studied, and they are available The recruitment of pro-caspase-1 through binding protein ASC activates the inflammatory corpuscles and activates the inactive pro-caspase-1 to mature caspase-1, resulting in the production and release of IL-1 beta and IL-18 and triggering the inflammatory reaction. And the role is rarely studied, especially in the central nervous system. Then whether NLRP2 is expressed in the central nervous system in the body and whether it is associated with cerebral ischemia, such as cerebral ischemia, is still needed to be further explored. In this experimental study, the model of the middle cerebral artery embolism (MCAO) and the glucose deprivation (OGD) model of the cultured cells were established. To explore the role and possible mechanism of NLRP2 in cerebral ischemia from two aspects in vivo and in vitro. Method 1 NLRP2 expression changes after cerebral ischemia in mice and the construction of cerebral ischemia model in 1.1 C57BL/6 wild type mice and neurology score 1.1.1 selected mice and construct ischemic model to select male wild type C57BL/6 experimental mice, weight 23g left Right, establish a middle cerebral artery embolism model. Neck median incision, incision of skin, separation of the left common carotid artery, internal carotid artery and external carotid artery under the microscope. The nylon thread plug is carefully inserted into the common carotid artery. When the cerebral blood flow meter detects the sudden drop of blood flow, it stops continuously and starts the time, after 12,24,48 hours, the mice are killed and taken to take mice fetch. Material.1.1.2 was used to evaluate the expression of NLRP2 in the brain of.1.2 after cerebral ischemia and its distribution and distribution of 1.2.1 using protein immunoblotting (Western blot, WB), Real-time PCR and immunohistochemistry (immunohistochemistry, IHC) for the detection of the changes in the expression of NLRP2 in the brain after cerebral ischemia. Immunofluorescence (IF) method for the detection of NLRP2 and the marker proteins of different cells in the brain of the mice, the distribution of NLRP2 in the brain, the construction of the.1.3 in vitro model and the detection of the original astrocytes by NLRP2 in vitro, and the establishment of oxygen deprivation (Oxygen Glucose Deprivation, OGD) model, respectively, for OGD. Treatment of 0.5,1,1.5,2h, Western blot (WB), tissue immunofluorescence (immunofluorescence, IF) and Real-time PCR detection of the expression of NLRP2 in the primary astrocytes after OGD;.2 NLRP2 in the brain ischemia injury in mice 2.1 injection of adeno-associated virus in mouse brain to use brain stereotaxis Injection of adeno-related virus vectors carrying NLRP2 silencing gene into specific parts of the nervous system by injection technique, the NLRP2 gene.2.2 injected into this site is injected into the brain of mice and the mice with NLRP2 silencing genes are injected into the brain. The brain of mice injected with NLRP2 silencing gene was stained with TTC, and the morphological damage was evaluated in.2.3 mice model of cerebral ischemia. CBA, Real-time PCR method was used to detect the level of pro-inflammatory factors in the brain homogenate of mice with NLRP2 silencing basis and.2. The effect of.4 NLRP2 on the apoptosis of primary astrocytes induced by OGD 2.4.1 the apoptosis of astrocytes transfected with 2.4.2 astrocytes, OGD treatment of astrocytes transfected with si-NLRP2, and the effect of Annexin V/PI staining on the apoptosis of primary astrocytes using flow cytometry to detect the apoptosis of astrocytes The regulation of NLRP2 pathway in.3 cerebral ischemia injury WB detection of NLRP2 effect on the level of Caspase-1, ASC, IL-1 beta in the brain of mice after cerebral ischemia The effect of NLRP2 on the expression of Caspase-1, p-p65, IL-1 beta in si-NLRP2 astrocytes after OGD treatment. Results 1 the expression of NLRP2 and its downstream molecules in the brain after cerebral ischemia in mice and the construction of the 1.1 C57BL/6 mouse model of cerebral ischemia and the neurology score were less than 2 in each group due to death or neurology score. The expression of NLRP2 in the brain of mice after.1.2 cerebral ischemia was removed and the distribution of NLRP2 in the brain of mice was removed and the distribution of 1.2.1 using protein immunoblotting (Western blot, WB), Real-time PCR and immunohistochemistry (immunohistochemistry, IHC) were used to detect the changes of NLRP2 expression after cerebral ischemia. We found that after cerebral ischemia, we found that the NLRP2 was after cerebral ischemia. The expression rose obviously and reached the peak in 24 hours. The results of immunohistochemical staining showed that.1.2.2 was mainly expressed in the primary astrocytes by immunofluorescence staining, and that NLRP2 was also expressed in the neurons. In the microglia, there was little expression of the expression of.1.3 in vitro model and the detection of NLRP2 in vitro. On behalf of astrocytes, the OGD model of oxygen deprivation was established. Through the analysis of WB and Real-time PCR, we found that the expression of NLRP2 increased significantly after OGD and reached the peak in OGD1.5 hours. The results of immunofluorescence showed that after the cell OGD1.5 hours, the expression of NLRP2 expression increased.2 NLRP2 in the cerebral ischemia injury of mice 2.1 injection of adeno-associated virus silencing. 4 weeks after the NLRP2 gene injection of the virus in the brain of mice, OCT was embedded in the brain tissue of mice. The scope of the virus infection was observed under the microscope under the microscope. The scope of the virus infection was larger, covering the.2.2 injection of the middle cerebral artery and the.2.2 virus with the NLRP2 silencing gene. After NLRP2 silencing gene cerebral ischemia, the neurology score of mice decreased obviously and the area of cerebral infarction decreased obviously. The detection of inflammatory factors in the.2.3 mice model of cerebral ischemia had cerebral ischemia treatment on mice injected with the virus and the virus injected with the NLRP2 silencing gene. The results of CBA and Real-time PCR showed the decline of NLRP2 expression caused by the injection virus. The effects of IL-1 beta, IL-18, IL-6, TNF- alpha MCP-1 and other inflammatory factors on the apoptosis of primary astrocytes induced by OGD can be alleviated by the flow cytometry results showed that the astrocytes transfected with si-NLRP2 were treated with OGD, and apoptotic astrocytes significantly reduced NLRP2 pathways in.3 cerebral ischemia. The WB results showed that the expression of NLRP2, caspase-1, ASC, IL-1 beta and other related proteins increased after cerebral ischemia in mice, and the mice injected with NLRP2 silencing genes decreased the NLRP2 expression compared with the mice injected with the empty virus, and the decrease of NLRP2 caused by the mice injected with the NLRP2 silent gene could reduce the cerebral ischemia. The associated proteins such as caspase-1, ASC, IL-1 beta and other related proteins were raised, and primary astrocytes were cultured. WB results showed that the expression of NLRP2 in siRNA-NLRP2 astrocytes decreased significantly. The decrease of NLRP2 expression caused by transfection of siRNA-NLRP2 cells could reduce caspase-1, p-p65, IL-I beta and other related proteins caused by OGD. This experiment is the first time to demonstrate the expression of NLRP2 in cerebral ischemia injury. It is found that the expression of NLRP2 increases after cerebral ischemia injury, which leads to the increase of Caspase-1, ASC, IL-1 beta and other related proteins, and the loss of NLRP2 can reduce the area of cerebral infarction and improve the cerebral ischemia injury, which has some preventive effect on cerebral ischemia.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743
本文编号：2152292
[Abstract]:In recent years, cerebral apoplexy is the main cause of long-term disability and death in the world, characterized by high morbidity, high mortality, high disability and high recurrence rate. Among them, ischemic stroke is more common than hemorrhagic stroke, with a proportion of more than 80%, which is due to obstruction of the brain artery to block the flow of blood to the brain. The pathophysiological process of ischemic cerebral apoplexy is complex and extensive, including oxidative stress, toxic effects of excitatory amino acids, energy metabolism disorders, changes in dynamic balance of cell ions, increased intracellular calcium levels, active oxygen mediated toxicity, and cytotoxic effects mediated by inflammatory cytokines. Recent studies have shown that the inflammatory response of the innate immune system is closely related to the process and progress of cerebral ischemia. The innate immune system is the first line of defense to restrict the undamaged host, and the intracellular and extracellular domain of the pattern recognition receptor (PRRs) can detect acute damage and initiate the inflammatory reaction. The oligomeric domain (NOD) - like receptor (NLRs) is a member of the intracellular pattern recognition receptor family and plays a key role in the inflammatory response. In the 22 category of human NLRs, 14 types include the thermal protein domain and form a NLRP subtype (NLRPs). In the NLRPs family, some members, such as NLRP1, NLRP3, and NLRP6, have been deeply studied, and they are available The recruitment of pro-caspase-1 through binding protein ASC activates the inflammatory corpuscles and activates the inactive pro-caspase-1 to mature caspase-1, resulting in the production and release of IL-1 beta and IL-18 and triggering the inflammatory reaction. And the role is rarely studied, especially in the central nervous system. Then whether NLRP2 is expressed in the central nervous system in the body and whether it is associated with cerebral ischemia, such as cerebral ischemia, is still needed to be further explored. In this experimental study, the model of the middle cerebral artery embolism (MCAO) and the glucose deprivation (OGD) model of the cultured cells were established. To explore the role and possible mechanism of NLRP2 in cerebral ischemia from two aspects in vivo and in vitro. Method 1 NLRP2 expression changes after cerebral ischemia in mice and the construction of cerebral ischemia model in 1.1 C57BL/6 wild type mice and neurology score 1.1.1 selected mice and construct ischemic model to select male wild type C57BL/6 experimental mice, weight 23g left Right, establish a middle cerebral artery embolism model. Neck median incision, incision of skin, separation of the left common carotid artery, internal carotid artery and external carotid artery under the microscope. The nylon thread plug is carefully inserted into the common carotid artery. When the cerebral blood flow meter detects the sudden drop of blood flow, it stops continuously and starts the time, after 12,24,48 hours, the mice are killed and taken to take mice fetch. Material.1.1.2 was used to evaluate the expression of NLRP2 in the brain of.1.2 after cerebral ischemia and its distribution and distribution of 1.2.1 using protein immunoblotting (Western blot, WB), Real-time PCR and immunohistochemistry (immunohistochemistry, IHC) for the detection of the changes in the expression of NLRP2 in the brain after cerebral ischemia. Immunofluorescence (IF) method for the detection of NLRP2 and the marker proteins of different cells in the brain of the mice, the distribution of NLRP2 in the brain, the construction of the.1.3 in vitro model and the detection of the original astrocytes by NLRP2 in vitro, and the establishment of oxygen deprivation (Oxygen Glucose Deprivation, OGD) model, respectively, for OGD. Treatment of 0.5,1,1.5,2h, Western blot (WB), tissue immunofluorescence (immunofluorescence, IF) and Real-time PCR detection of the expression of NLRP2 in the primary astrocytes after OGD;.2 NLRP2 in the brain ischemia injury in mice 2.1 injection of adeno-associated virus in mouse brain to use brain stereotaxis Injection of adeno-related virus vectors carrying NLRP2 silencing gene into specific parts of the nervous system by injection technique, the NLRP2 gene.2.2 injected into this site is injected into the brain of mice and the mice with NLRP2 silencing genes are injected into the brain. The brain of mice injected with NLRP2 silencing gene was stained with TTC, and the morphological damage was evaluated in.2.3 mice model of cerebral ischemia. CBA, Real-time PCR method was used to detect the level of pro-inflammatory factors in the brain homogenate of mice with NLRP2 silencing basis and.2. The effect of.4 NLRP2 on the apoptosis of primary astrocytes induced by OGD 2.4.1 the apoptosis of astrocytes transfected with 2.4.2 astrocytes, OGD treatment of astrocytes transfected with si-NLRP2, and the effect of Annexin V/PI staining on the apoptosis of primary astrocytes using flow cytometry to detect the apoptosis of astrocytes The regulation of NLRP2 pathway in.3 cerebral ischemia injury WB detection of NLRP2 effect on the level of Caspase-1, ASC, IL-1 beta in the brain of mice after cerebral ischemia The effect of NLRP2 on the expression of Caspase-1, p-p65, IL-1 beta in si-NLRP2 astrocytes after OGD treatment. Results 1 the expression of NLRP2 and its downstream molecules in the brain after cerebral ischemia in mice and the construction of the 1.1 C57BL/6 mouse model of cerebral ischemia and the neurology score were less than 2 in each group due to death or neurology score. The expression of NLRP2 in the brain of mice after.1.2 cerebral ischemia was removed and the distribution of NLRP2 in the brain of mice was removed and the distribution of 1.2.1 using protein immunoblotting (Western blot, WB), Real-time PCR and immunohistochemistry (immunohistochemistry, IHC) were used to detect the changes of NLRP2 expression after cerebral ischemia. We found that after cerebral ischemia, we found that the NLRP2 was after cerebral ischemia. The expression rose obviously and reached the peak in 24 hours. The results of immunohistochemical staining showed that.1.2.2 was mainly expressed in the primary astrocytes by immunofluorescence staining, and that NLRP2 was also expressed in the neurons. In the microglia, there was little expression of the expression of.1.3 in vitro model and the detection of NLRP2 in vitro. On behalf of astrocytes, the OGD model of oxygen deprivation was established. Through the analysis of WB and Real-time PCR, we found that the expression of NLRP2 increased significantly after OGD and reached the peak in OGD1.5 hours. The results of immunofluorescence showed that after the cell OGD1.5 hours, the expression of NLRP2 expression increased.2 NLRP2 in the cerebral ischemia injury of mice 2.1 injection of adeno-associated virus silencing. 4 weeks after the NLRP2 gene injection of the virus in the brain of mice, OCT was embedded in the brain tissue of mice. The scope of the virus infection was observed under the microscope under the microscope. The scope of the virus infection was larger, covering the.2.2 injection of the middle cerebral artery and the.2.2 virus with the NLRP2 silencing gene. After NLRP2 silencing gene cerebral ischemia, the neurology score of mice decreased obviously and the area of cerebral infarction decreased obviously. The detection of inflammatory factors in the.2.3 mice model of cerebral ischemia had cerebral ischemia treatment on mice injected with the virus and the virus injected with the NLRP2 silencing gene. The results of CBA and Real-time PCR showed the decline of NLRP2 expression caused by the injection virus. The effects of IL-1 beta, IL-18, IL-6, TNF- alpha MCP-1 and other inflammatory factors on the apoptosis of primary astrocytes induced by OGD can be alleviated by the flow cytometry results showed that the astrocytes transfected with si-NLRP2 were treated with OGD, and apoptotic astrocytes significantly reduced NLRP2 pathways in.3 cerebral ischemia. The WB results showed that the expression of NLRP2, caspase-1, ASC, IL-1 beta and other related proteins increased after cerebral ischemia in mice, and the mice injected with NLRP2 silencing genes decreased the NLRP2 expression compared with the mice injected with the empty virus, and the decrease of NLRP2 caused by the mice injected with the NLRP2 silent gene could reduce the cerebral ischemia. The associated proteins such as caspase-1, ASC, IL-1 beta and other related proteins were raised, and primary astrocytes were cultured. WB results showed that the expression of NLRP2 in siRNA-NLRP2 astrocytes decreased significantly. The decrease of NLRP2 expression caused by transfection of siRNA-NLRP2 cells could reduce caspase-1, p-p65, IL-I beta and other related proteins caused by OGD. This experiment is the first time to demonstrate the expression of NLRP2 in cerebral ischemia injury. It is found that the expression of NLRP2 increases after cerebral ischemia injury, which leads to the increase of Caspase-1, ASC, IL-1 beta and other related proteins, and the loss of NLRP2 can reduce the area of cerebral infarction and improve the cerebral ischemia injury, which has some preventive effect on cerebral ischemia.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743
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