为了研究高原动物对青藏高原高寒、低氧等极端生境的适应机理,进一步探讨高原动物对高原反应——高原脑水肿抗性的分子机理,运用基因克隆与生物信息学相关技术和方法,对牦牛脑AQP4(水通道蛋白4,AQP4)基因CDS全长序列进行克隆、基因序列...为了研究高原动物对青藏高原高寒、低氧等极端生境的适应机理,进一步探讨高原动物对高原反应——高原脑水肿抗性的分子机理,运用基因克隆与生物信息学相关技术和方法,对牦牛脑AQP4(水通道蛋白4,AQP4)基因CDS全长序列进行克隆、基因序列比对及其生物信息学特征分析。结果表明,牦牛AQP4的CDS含有一个966 bp的开放阅读框,编码322个氨基酸;牦牛AQP4基因编码蛋白分子量34.69 k D,理论等电点(p I)7.59,其编码蛋白含有6次跨膜结构,属于疏水性蛋白;二级结构主要由α-螺旋、延伸及无规则卷曲构成;AQP4基因编码产物氨基酸同源性及系统进化分析发现,牦牛AQP4基因编码氨基酸序列与黄牛、绵羊等物种间同源性较高,系统进化情况与其亲缘关系远近一致。展开更多
Brain edema is a common feature of several brain diseases(e.g.,stroke,traumatic brain injury,hydrocephalus,brain cancer,and brain infections).Brain edema leads to increased intracranial pressure and worsens outcomes i...Brain edema is a common feature of several brain diseases(e.g.,stroke,traumatic brain injury,hydrocephalus,brain cancer,and brain infections).Brain edema leads to increased intracranial pressure and worsens outcomes in ischemic stroke patients.Conventional treatments to control brain edema,thus reducing intracranial pressure include different osmotherapeutics,hyperventilation,tromethamine,hypothermia,and barbiturate coma.However,level 1 evidence of efficacy is lacking for these treatments,with some being harmful rather than beneficial(Bardutzky and Schwab,2007).It has been proposed aquaporin 4(AQP4)can be a novel drug target for treating brain edema(Vandebroek and Yasui,2020).展开更多
Objective:To study the expression of miRNA 320 a in the brain tissue of epileptic rats and analyze its effect on the expression of aquaporin 4(AQP4).Methods:All rats were performed with the intraperitoneal injection o...Objective:To study the expression of miRNA 320 a in the brain tissue of epileptic rats and analyze its effect on the expression of aquaporin 4(AQP4).Methods:All rats were performed with the intraperitoneal injection of lithium chloride(3 mmol/kg) and then the intraperitoneal injection of pilocarpine(30 mg/kg) 24 h later(injected twice) to prepare the epileptic model of Wistar rats.Rats in the control group were injected with the equal volume of normal saline.According to the Racine scale,rats with over stage 3 of epilepsy were chosen and the brain tissue was separated quickly and then stored at-80 ℃.The immunohistochemistry was used to detect the expression of aquaporin in the brain tissue of epileptic model and the Real-time PCR was employed to determine the difference in the expression of miRNA 320 a and AQP4 in the brain tissue of rats between the epileptic model group and control one.Five 5-day neonatal Wistar rats were chosen to collect the cerebral cortex and their primary astrocytes were separated and cultured.They were transfected with miRNA mimic and imitated to the endogenous miRNA 320 a to up-regulate the expression of miRNA 320 a.Results:In the model group,the expression of AQP4 was significantly higher than the control group(P<0.01).However,the expression of miRNA 320 a in the model group was lower than control group(P<0.05),which was negatively correlated to AQP4.In the primary astrocytes,the transfection of miRNA 320 a mimic could significantly reduce the expression of AQP4,while its inhibitor could up-regulate the expression of AQP4,which indicated that miRNA 320 a could reduce the expression of AQP4.Conclusions:In the primary astrocytes of rats,the miRNA 320 a could inhibit the expression of AQP4 and after adding the inhibitor of miRNA 320 a,the expression of AQP4 was up-regulated.展开更多
文摘为了研究高原动物对青藏高原高寒、低氧等极端生境的适应机理,进一步探讨高原动物对高原反应——高原脑水肿抗性的分子机理,运用基因克隆与生物信息学相关技术和方法,对牦牛脑AQP4(水通道蛋白4,AQP4)基因CDS全长序列进行克隆、基因序列比对及其生物信息学特征分析。结果表明,牦牛AQP4的CDS含有一个966 bp的开放阅读框,编码322个氨基酸;牦牛AQP4基因编码蛋白分子量34.69 k D,理论等电点(p I)7.59,其编码蛋白含有6次跨膜结构,属于疏水性蛋白;二级结构主要由α-螺旋、延伸及无规则卷曲构成;AQP4基因编码产物氨基酸同源性及系统进化分析发现,牦牛AQP4基因编码氨基酸序列与黄牛、绵羊等物种间同源性较高,系统进化情况与其亲缘关系远近一致。
基金supported by the NSW Ministry of Health, Australia under the NSW Health Early-Mid Career Fellowships Schemethe Australian Academy of Technology and Engineering(ATSE)under the Global Connections Fund+1 种基金supported by research grants received from the Wellcome Trust(200633/z/16/z)Keele University
文摘Brain edema is a common feature of several brain diseases(e.g.,stroke,traumatic brain injury,hydrocephalus,brain cancer,and brain infections).Brain edema leads to increased intracranial pressure and worsens outcomes in ischemic stroke patients.Conventional treatments to control brain edema,thus reducing intracranial pressure include different osmotherapeutics,hyperventilation,tromethamine,hypothermia,and barbiturate coma.However,level 1 evidence of efficacy is lacking for these treatments,with some being harmful rather than beneficial(Bardutzky and Schwab,2007).It has been proposed aquaporin 4(AQP4)can be a novel drug target for treating brain edema(Vandebroek and Yasui,2020).
基金supported by China-US Collaborative Program on Emerging Infectious Diseases(U19-GH000004)Special Project of Major Infectious Diseases by Ministry of Science and Technology(2003BA712A08-01)General Program of National Natural Science Foundation of China(81171635/H1912)
文摘Objective:To study the expression of miRNA 320 a in the brain tissue of epileptic rats and analyze its effect on the expression of aquaporin 4(AQP4).Methods:All rats were performed with the intraperitoneal injection of lithium chloride(3 mmol/kg) and then the intraperitoneal injection of pilocarpine(30 mg/kg) 24 h later(injected twice) to prepare the epileptic model of Wistar rats.Rats in the control group were injected with the equal volume of normal saline.According to the Racine scale,rats with over stage 3 of epilepsy were chosen and the brain tissue was separated quickly and then stored at-80 ℃.The immunohistochemistry was used to detect the expression of aquaporin in the brain tissue of epileptic model and the Real-time PCR was employed to determine the difference in the expression of miRNA 320 a and AQP4 in the brain tissue of rats between the epileptic model group and control one.Five 5-day neonatal Wistar rats were chosen to collect the cerebral cortex and their primary astrocytes were separated and cultured.They were transfected with miRNA mimic and imitated to the endogenous miRNA 320 a to up-regulate the expression of miRNA 320 a.Results:In the model group,the expression of AQP4 was significantly higher than the control group(P<0.01).However,the expression of miRNA 320 a in the model group was lower than control group(P<0.05),which was negatively correlated to AQP4.In the primary astrocytes,the transfection of miRNA 320 a mimic could significantly reduce the expression of AQP4,while its inhibitor could up-regulate the expression of AQP4,which indicated that miRNA 320 a could reduce the expression of AQP4.Conclusions:In the primary astrocytes of rats,the miRNA 320 a could inhibit the expression of AQP4 and after adding the inhibitor of miRNA 320 a,the expression of AQP4 was up-regulated.
