In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allos...In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam （30-90 IJM） decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2CI cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.展开更多
目的探讨γ-氨基丁酸B受体B1亚单位（GA BA BR1）基因（G1465A）多态性及前强啡肽原（PDYN）启动子区基因多态性与汉族人群脑梗死继发癫痫发生之间的关系。方法选择郑州大学第五、第一附属医院神经内科自2010年7月至2011年8月住院及门...目的探讨γ-氨基丁酸B受体B1亚单位（GA BA BR1）基因（G1465A）多态性及前强啡肽原（PDYN）启动子区基因多态性与汉族人群脑梗死继发癫痫发生之间的关系。方法选择郑州大学第五、第一附属医院神经内科自2010年7月至2011年8月住院及门诊收治的67例脑梗死继发癫痫患者、同期收治的93例脑梗死无癫痫患者和104例体检正常者为研究对象．采集各组对象肘静脉血，柱层析法提取血细胞基因组DNA，聚合酶链式反应-限制性片段长度多态（PCR-RFLP）技术检测GA BA BRl基因（G1465A）多态性，聚合酶链式反应（PCR）技术检测PDYN启动子区基因多态性。结果3组研究对象酬鲋BRJ基因（Gl465A）都显示为G／G型，未发现A／G型和A／A型。脑梗死继发癫痫组中PDYN启动子区基因L／L型频率（76．1％）略高于脑梗死无癫痫组（73．2％）及正常对照组（73．1％），L型等位基因频率（85．8％）略高于脑梗死无癫痫组（85．5％）及正常对照组（84．6％），3组间基因型频率和等位基因频率比较差异均无统计学意义（P＞O．05）。结论GABABRJ基因（G1465A）及PDYN启动子区基因多态性与汉族人群脑梗死继发癫痫可能无明显关系。展开更多
Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, ...Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.展开更多
基金support from the National Natural Science Foundation of China,No.30571791
文摘In many recent studies, the inhibitory transmitter gamma-aminobutyric acid has been shown to modulate the proliferation, differentiation and survival of neural stem cells. Most general anesthetics are partial or allosteric gamma-aminobutyric acid A receptor agonists, suggesting that general anesthetics could alter the behavior of neural stem cells. The neuroprotective efficacy of general anesthetics has been recognized for decades, but their effects on the proliferation of neural stem cells have received little attention. This study investigated the potential effect of midazolam, an extensively used general anesthetic and allosteric gamma-aminobutyric acid A receptor agonist, on the proliferation of neural stem cells in vitro and preliminarily explored the underlying mechanism. The proliferation of neural stem cells was tested using both Cell Counting Kit 8 and bromodeoxyuridine incorporation experiments. Cell distribution analysis was performed to describe changes in the cell cycle distribution in response to midazolam. Calcium imaging was employed to explore the molecular signaling pathways activated by midazolam. Midazolam （30-90 IJM） decreased the proliferation of neural stem cells in vitro. Pretreatment with the gamma-aminobutyric acid A receptor antagonist bicuculline or Na-K-2CI cotransport inhibitor furosemide partially rescued this inhibition. In addition, midazolam triggered a calcium influx into neural stem cells. The suppressive effect of midazolam on the proliferation of neural stem cells can be partly attributed to the activation of gamma-aminobutyric acid A receptor. The calcium influx triggered by midazolam may be a trigger factor leading to further downstream events.
文摘目的探讨γ-氨基丁酸B受体B1亚单位（GA BA BR1）基因（G1465A）多态性及前强啡肽原（PDYN）启动子区基因多态性与汉族人群脑梗死继发癫痫发生之间的关系。方法选择郑州大学第五、第一附属医院神经内科自2010年7月至2011年8月住院及门诊收治的67例脑梗死继发癫痫患者、同期收治的93例脑梗死无癫痫患者和104例体检正常者为研究对象．采集各组对象肘静脉血，柱层析法提取血细胞基因组DNA，聚合酶链式反应-限制性片段长度多态（PCR-RFLP）技术检测GA BA BRl基因（G1465A）多态性，聚合酶链式反应（PCR）技术检测PDYN启动子区基因多态性。结果3组研究对象酬鲋BRJ基因（Gl465A）都显示为G／G型，未发现A／G型和A／A型。脑梗死继发癫痫组中PDYN启动子区基因L／L型频率（76．1％）略高于脑梗死无癫痫组（73．2％）及正常对照组（73．1％），L型等位基因频率（85．8％）略高于脑梗死无癫痫组（85．5％）及正常对照组（84．6％），3组间基因型频率和等位基因频率比较差异均无统计学意义（P＞O．05）。结论GABABRJ基因（G1465A）及PDYN启动子区基因多态性与汉族人群脑梗死继发癫痫可能无明显关系。
基金This study was partially supported by the National Natural Science Foundation of China （No. 30971303）.
文摘Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.
