目的:探讨丁苯酚联合尼莫地平对急性脑出血患者及神经功能及血清基质金属蛋白酶9(MMP-9)和核转录因子kappa B(NF-κB)水平的影响。方法:选择90例急性脑出血患者作为研究对象并将其随机分为两组,每组各45例。两组患者均给予口服尼莫地平...目的:探讨丁苯酚联合尼莫地平对急性脑出血患者及神经功能及血清基质金属蛋白酶9(MMP-9)和核转录因子kappa B(NF-κB)水平的影响。方法:选择90例急性脑出血患者作为研究对象并将其随机分为两组,每组各45例。两组患者均给予口服尼莫地平片治疗,观察组在对照组基础上加以口服丁苯酚软胶囊,疗程均为30天。比较两组患者的临床疗效以及治疗前后血清MMP-9、NF-κB水平和神经功能的变化。结果:观察组患者的临床总有效率显著高于对照组[42(93.99%)vs 37(82.22%)](P<0.05)。治疗后,观察组的血清MMP-9、NF-κB水平均明显低于对照组[121.51±14.76 vs 137.09±14.71;0.14±0.04vs0.24±0.05](P<0.05),日常生活质量评分(ADL)明显高于对照组[37.09±5.91 vs 33.54±6.74](P<0.05),神经功能缺损评分(NIHSS)明显低于对照组[15.31±7.61 vs18.54±5.21](P<0.05),认知功能评分(MMSE)明显高于对照组[27.54±4.21vs23.72±5.75](P<0.05)。结论:丁苯酚联合尼莫地平治疗急性脑出血患者的临床疗效优于口服尼莫地平片单药治疗,可有效改善患者的神经和认知功能,可能与其显著降低血清MMP-9、NF-κB水平有关。展开更多
目的观察和评价丁苯酞注射液治疗进展性脑卒中(PS)的有效性和安全性。方法选取2011—2014年于福建省立医院神经内科住院治疗符合纳入与排除标准的PS患者140例为研究对象。采用随机数字表法将患者分为丁苯酞组和对照组各70例。研究过程...目的观察和评价丁苯酞注射液治疗进展性脑卒中(PS)的有效性和安全性。方法选取2011—2014年于福建省立医院神经内科住院治疗符合纳入与排除标准的PS患者140例为研究对象。采用随机数字表法将患者分为丁苯酞组和对照组各70例。研究过程中失访6例,其中丁苯酞组2例,对照组4例,将其删除。丁苯酞组给予基础治疗+丁苯酞注射液治疗,对照组给予基础治疗。首诊时、进展后、治疗后14 d和治疗后90 d采用美国国立卫生研究院卒中量表(NIHSS)评分以及NIHSS评分进展幅度评估神经功能障碍程度;治疗后14 d和治疗后90 d采用NIHSS评分演变情况评估神经功能转归情况;治疗后14 d和治疗后90 d采用Barthel指数评估治疗后日常生活能力;治疗后90 d应用改良Rankin量表(mRS)评分评估神经功能障碍康复程度,将mRS评分≤2.0分定义为预后良好,mRS评分>2.0分定义为预后不良事件。对两组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者的NIHSS评分、Barthel指数、mRS评分进行比较分析。观察有无皮疹等过敏反应及其他不良事件。结果两组治疗后14 d、治疗后90 d NIHSS评分均低于进展后,治疗后90 d NIHSS评分均低于治疗后14 d(P<0.05)。丁苯酞组治疗后14 d、治疗后90 d NIHSS评分降低率均高于对照组(P<0.05)。丁苯酞组治疗后14 d、治疗后90 d Barthel指数、预后良好率高于对照组,治疗后90 d mRS评分低于对照组(P<0.05)。共发现61例(45.5%)脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变,其中丁苯酞组29例(42.6%),对照组32例(48.5%)。丁苯酞组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者治疗后14 d、治疗后90 d NIHSS评分低于进展后,治疗后90 d NIHSS评分低于治疗后14 d(P<0.05)。丁苯酞组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者治疗后14 d Barthel指数、治疗后90 d Barthel指数、预后良好率均高于对照组(P<展开更多
Background Amyotrophic lateral sclerosis （ALS） is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the huma...Background Amyotrophic lateral sclerosis （ALS） is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide （DL-NBP） for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model. Methods Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg.kg-1.d-~ DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg.kgl.d1, respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation （MUNE） technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantJtation was performed by Nissl staining and microglia activation was observed by immunohistochemistry. Results Oral administration of 60 mg.kg-l-d-1 DL-NBP significantly prolonged survival （（164.78±16.67） days） of SOD1-G93A mice compared with vehicle control （（140.00＋16.89） days）. Treating mice with DL-NBP （60 mg.kg-1.d-1） significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP （60 mg.kgl.d1） slowed the rate of MUNE reduction （P 〈0.01）. Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP （60 mg.kg-1d-1） at the stage of 19 weeks （P 〈0.01）. Treating mice with DL-NBP （60 mg.kg1.d1） si展开更多
Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on o...Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on oxygen glucose deprivation-induced hypoxia inducible factor-1α expression.In this study,we hypothesized that DL-3-n-butylphthalide can protect against oxygen glucose deprivation-induced injury of newborn rat brain microvascular endothelial cells by means of upregulating hypoxia inducible factor-1α expression.MTT assay and Hoechst staining results showed that DL-3-n-butylphthalide protected brain microvascular endothelial cells against oxygen glucose deprivation-induced injury in a dose-dependent manner.Western blot and immunofluorescent staining results further confirmed that the protective effect was related to upregulation of hypoxia inducible factor-1α.Real-time RT-PCR reaction results showed that DL-3-n-butylphthalide reduced apoptosis by inhibiting downregulation of pro-apoptotic gene caspase-3 mRNA expression and upregulation of apoptosis-executive protease bcl-2 mRNA expression;however,DL-3-n-butylphthalide had no protective effects on brain microvascular endothelial cells after knockdown of hypoxia inducible factor-1α by small interfering RNA.These findings suggest that DL-3-n-butylphthalide can protect brain microvascular endothelial cells against oxygen glucose deprivation-induced injury by upregulating bcl-2 expression and downregulating caspase-3 expression though hypoxia inducible factor-1α pathway.展开更多
BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP...BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity 展开更多
文摘目的:探讨丁苯酚联合尼莫地平对急性脑出血患者及神经功能及血清基质金属蛋白酶9(MMP-9)和核转录因子kappa B(NF-κB)水平的影响。方法:选择90例急性脑出血患者作为研究对象并将其随机分为两组,每组各45例。两组患者均给予口服尼莫地平片治疗,观察组在对照组基础上加以口服丁苯酚软胶囊,疗程均为30天。比较两组患者的临床疗效以及治疗前后血清MMP-9、NF-κB水平和神经功能的变化。结果:观察组患者的临床总有效率显著高于对照组[42(93.99%)vs 37(82.22%)](P<0.05)。治疗后,观察组的血清MMP-9、NF-κB水平均明显低于对照组[121.51±14.76 vs 137.09±14.71;0.14±0.04vs0.24±0.05](P<0.05),日常生活质量评分(ADL)明显高于对照组[37.09±5.91 vs 33.54±6.74](P<0.05),神经功能缺损评分(NIHSS)明显低于对照组[15.31±7.61 vs18.54±5.21](P<0.05),认知功能评分(MMSE)明显高于对照组[27.54±4.21vs23.72±5.75](P<0.05)。结论:丁苯酚联合尼莫地平治疗急性脑出血患者的临床疗效优于口服尼莫地平片单药治疗,可有效改善患者的神经和认知功能,可能与其显著降低血清MMP-9、NF-κB水平有关。
文摘目的观察和评价丁苯酞注射液治疗进展性脑卒中(PS)的有效性和安全性。方法选取2011—2014年于福建省立医院神经内科住院治疗符合纳入与排除标准的PS患者140例为研究对象。采用随机数字表法将患者分为丁苯酞组和对照组各70例。研究过程中失访6例,其中丁苯酞组2例,对照组4例,将其删除。丁苯酞组给予基础治疗+丁苯酞注射液治疗,对照组给予基础治疗。首诊时、进展后、治疗后14 d和治疗后90 d采用美国国立卫生研究院卒中量表(NIHSS)评分以及NIHSS评分进展幅度评估神经功能障碍程度;治疗后14 d和治疗后90 d采用NIHSS评分演变情况评估神经功能转归情况;治疗后14 d和治疗后90 d采用Barthel指数评估治疗后日常生活能力;治疗后90 d应用改良Rankin量表(mRS)评分评估神经功能障碍康复程度,将mRS评分≤2.0分定义为预后良好,mRS评分>2.0分定义为预后不良事件。对两组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者的NIHSS评分、Barthel指数、mRS评分进行比较分析。观察有无皮疹等过敏反应及其他不良事件。结果两组治疗后14 d、治疗后90 d NIHSS评分均低于进展后,治疗后90 d NIHSS评分均低于治疗后14 d(P<0.05)。丁苯酞组治疗后14 d、治疗后90 d NIHSS评分降低率均高于对照组(P<0.05)。丁苯酞组治疗后14 d、治疗后90 d Barthel指数、预后良好率高于对照组,治疗后90 d mRS评分低于对照组(P<0.05)。共发现61例(45.5%)脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变,其中丁苯酞组29例(42.6%),对照组32例(48.5%)。丁苯酞组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者治疗后14 d、治疗后90 d NIHSS评分低于进展后,治疗后90 d NIHSS评分低于治疗后14 d(P<0.05)。丁苯酞组脑梗死病灶同侧颈内动脉系统的狭窄闭塞性病变患者治疗后14 d Barthel指数、治疗后90 d Barthel指数、预后良好率均高于对照组(P<
基金FENG Xin-hong and YUAN Wei contributed equally to the work. The study was supported by the grants from National Natural Science Foundation of China （No. 30971002 and No. 30911120496）.
文摘Background Amyotrophic lateral sclerosis （ALS） is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide （DL-NBP） for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model. Methods Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg.kg-1.d-~ DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg.kgl.d1, respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation （MUNE） technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantJtation was performed by Nissl staining and microglia activation was observed by immunohistochemistry. Results Oral administration of 60 mg.kg-l-d-1 DL-NBP significantly prolonged survival （（164.78±16.67） days） of SOD1-G93A mice compared with vehicle control （（140.00＋16.89） days）. Treating mice with DL-NBP （60 mg.kg-1.d-1） significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP （60 mg.kgl.d1） slowed the rate of MUNE reduction （P 〈0.01）. Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP （60 mg.kg-1d-1） at the stage of 19 weeks （P 〈0.01）. Treating mice with DL-NBP （60 mg.kg1.d1） si
基金supported by the National Natural Science Foundation of China,No.30471917 and 30770766
文摘Studies have demonstrated that DL-3-n-butylphthalide can significantly alleviate oxygen glucose deprivation-induced injury of human umbilical vein endothelial cells at least partly associated with its enhancement on oxygen glucose deprivation-induced hypoxia inducible factor-1α expression.In this study,we hypothesized that DL-3-n-butylphthalide can protect against oxygen glucose deprivation-induced injury of newborn rat brain microvascular endothelial cells by means of upregulating hypoxia inducible factor-1α expression.MTT assay and Hoechst staining results showed that DL-3-n-butylphthalide protected brain microvascular endothelial cells against oxygen glucose deprivation-induced injury in a dose-dependent manner.Western blot and immunofluorescent staining results further confirmed that the protective effect was related to upregulation of hypoxia inducible factor-1α.Real-time RT-PCR reaction results showed that DL-3-n-butylphthalide reduced apoptosis by inhibiting downregulation of pro-apoptotic gene caspase-3 mRNA expression and upregulation of apoptosis-executive protease bcl-2 mRNA expression;however,DL-3-n-butylphthalide had no protective effects on brain microvascular endothelial cells after knockdown of hypoxia inducible factor-1α by small interfering RNA.These findings suggest that DL-3-n-butylphthalide can protect brain microvascular endothelial cells against oxygen glucose deprivation-induced injury by upregulating bcl-2 expression and downregulating caspase-3 expression though hypoxia inducible factor-1α pathway.
基金Supported by:the Medicine and Health Scientific Research Projects of Shandong Province,No. 2007HZ065
文摘BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity
