DL-3-n-butylphthalide alleviates motor disturbance by suppressing ferroptosis in a rat model of Parkinson’s disease

DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.

依达拉奉联合Dl-3-正丁基苯酞软胶囊治疗进展型脑梗死40例临床观察

将同期收治的120例进展型脑梗死患者随机分为A、B、C组各40例,三组均予低分子右旋糖酐、胞二磷胆碱等常规治疗,在此基础上A组予依达拉奉静滴、Dl-3-正丁基苯酞软胶囊口服;B组静滴依达拉奉,方法剂量同上;C组予复方丹参静滴,均14 d为一疗程。观察三组疗效及症状评分。结果A、B、C组显效率均显著高于C组(P<0.05);治疗后症状评分均显著低于治疗前及C组,A组低于B组。认为依达拉奉联合Dl-3-正丁基苯酞软胶囊对进展型脑梗死有协同治疗效果。

HCHO-(DL-苹果酸)-BrO_3^--Mn^(2+)H_2SO_4体系化学振荡反应动力学研究

研究了HCHO参与下的(DL 苹果酸) BrO-3 Mn2+ H2SO4化学振荡反应体系的非线性动力学行为,考察了该体系中各反应物的初始浓度范围及主要影响因素.结果表明,在5.0×10-5～1.0×10-2mol·L-1范围内,HCHO对振荡反应的诱导期和周期有较大影响,且HCHO浓度的对数lnc(HCHO)与诱导期倒数的对数ln(1/tin)及周期倒数的对数ln(1/tp)均存在线性关系.诱导期和周期的表观活化参数分别为70.87,55.71kJ·mol-1.另外还对HCHO参与下的可能振荡反应机理进行了探讨.

手性酒石酸酯对不对称环氧化反应动力学拆分DL-1-十四烯-3-醇的催化选择性

利用Sharpless不对称环氧化反应动力学拆分二级烯丙醇DL 1 十四烯 3 醇 ,研究了不同手性酒石酸酯催化剂 [酒石酸乙酯 (DET)、酒石酸异丙酯 (DIPT)、酒石酸环己酯 (DCHT)以及酒石酸环十二酯 (DCDT) ]对该反应的催化选择性 ,拆分所得的烯丙醇的光学纯度有一定差异 ,从 90 %到 99%ee .

dl-3-正丁基苯酞软胶囊治疗急性进展性脑梗死疗效观察

目的观察dl-3-正丁基苯酞软胶囊治疗急性进展性脑梗死的疗效。方法将60例脑梗死患者随机分为治疗组和对照组,各30例。对照组给予血栓通加入生理盐水静脉输注,每日1次。治疗组在此基础上给予丁苯酞软胶囊口服,疗程为2周。评价两组患者在治疗前及治疗后第7天、第14天的神经功能缺损程度。结果治疗组治疗第7天和第14天的临床神经功能缺损程度评分较治疗前均显著降低(P<0.05),且与对照组治疗后比较差异有统计学意义(P<0.05)。结论 dl-3-正丁基苯酞软胶囊对急性进展性脑梗死的治疗具有显著效果。

多巴丝肼联用dl-3-正丁基苯酞对脑卒中患者患侧上肢功能的影响

目的观察多巴丝肼联用dl-3-正丁基苯酞对脑卒中患者患侧上肢功能恢复的影响。方法 90例脑卒中偏瘫患者采用随机数字表法分为康复组、治疗组及对照组,每组30例。康复组和治疗组患者均给予运动疗法治疗,其中治疗组患者加用口服多巴丝肼、dl-3-正丁基苯酞治疗。分别于治疗前、治疗8周时采用运动功能评分(FMA)、运动功能评估量表(MAS)对患者上肢功能进行评定。结果治疗前患者上肢FMA、MAS评分差异无显著性;治疗8周后,康复组和治疗组患者上肢FMA及MAS评分均较治疗前改善,治疗组较康复组改善,且均优于对照组。结论多巴丝肼联用dl-3-正丁基苯酞胶囊可进一步改善患者上肢运动功能。

多巴丝肼联合dl-3-正丁基苯酞对脑梗死患者患侧上肢功能的影响

目的观察多巴丝肼联用dl-3-正丁基苯酞对脑梗死患者患侧上肢功能恢复的影响。方法 90例脑梗死恢复期偏瘫患者,采用随机数字表法将其分为康复组、治疗组及对照组,每组30例。均给予运动疗法治疗,治疗组患者加用口服多巴丝肼、dl-3-正丁基苯酞治疗,对照组给予形状相似的对照物口服。分别于治疗前、治疗8周时采用运动功能评分(FMA)、运动功能评估量表(MAS)对患者上肢功能进行评定。结果治疗前三组患者上肢FMA及MAS评分差异无显著性;治疗8周后,康复组、治疗组患者上肢FMA及MAS评分均较治疗前改善;对照组与治疗前比较差异无显著性;治疗组治疗后上肢FMA及MAS评分优于康复组、对照组水平。结论多巴丝肼联用dl-3-正丁基苯酞胶囊可进一步改善患者上肢运动功能。

dl-3-正丁基苯酞软胶囊治疗椎-基底动脉供血不足疗效观察

目的:评价dl-3-正丁基苯酞软胶囊治疗椎-基底动脉供血不足的临床疗效。方法:收集椎-基底动脉供血不足患者124例,其中,治疗组66例采用dl-3-正丁基苯酞软胶囊治疗,对照组58例采用复方丹参片治疗。60d后观察两组的临床疗效。结果:治疗组总有效率为87.88%(58/66),对照组总有效率为68.97%(40/58),差异有统计学意义(P<0.05)。结论:dl-3-正丁基苯酞软胶囊对椎-基底动脉供血不足有明显疗效。

Hypoxia inducible factor-1alpha mediates protection of DL-3-n-butylphthalide in brain microvascular endothelial cells against oxygen glucose deprivation-induced injury

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.

DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia

Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

DI-3-n-butylphthalide exerts neuroprotective effects by modulating hypoxia-inducible factor 1-alpha ubiquitination to attenuate oxidative stress-induced apoptosis

DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.

Dl-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

新型吡唑类化合物DL-1的硝化抑制效应初探

以国内外应用较为广泛的硝化抑制剂双氰胺(DCD)为参比对象,采用室内培养方法,对新型吡唑类化合物DL-1的硝化抑制效应进行初步探讨.结果表明,DL-1对土壤中铵的氧化过程具有显著的抑制效应,前3周的硝化抑制率可达70%以上,且硝化抑制能力在第14天至28天最强.与等量DCD相比,施用量为(NH4)2SO4氮量1.0%的DL-1在14、21和28d使土壤中的NO3--N含量分别下降26.23%、33.27%和23.31%;与不加抑制剂的对照处理相比,土壤NO3--N含量则分别下降了71.12%、69.10%和55.14%.当DL-1用量为(NH4)2SO4氮量的2.0%时,土壤的硝化作用受到了更强烈的抑制,到培养第90天试验结束,土壤中的NO3--N含量始终维持在较低水平.

X衍射精细结构和晶体旋光角研究D-,L-,DL-缬氨酸晶格分子间N^+H…O^-氢键电子库珀对的自旋流超导相变(英文)

为了解决D-和L-缬氨酸单晶在～270 K相变的机理和分岐,以比热法测定单晶、多晶粉末及Sigma多晶产品发现,只有D-和L-缬氨酸单晶发生相变,且为吸热反应,能差0.18 J·mol-1.本文以Mo-Kα(λ=0.071073nm)为光源的X衍射精确测定表明,D-/L-缬氨酸单晶属于单斜空间点群P21,Z=4.在相变温度～270 K,其晶格常数分别为:a=0.96706(5)/0.96737(5)nm,b=0.52680(3)/0.52664(3)nm,c=1.20256(7)/1.20196(6)nm,β=90.724(2)°/90.722(3)°.在晶体结构的单元细胞中,含有两种转动异构体:A(trans)和B(gauche I).温度为293、270、223、173 K的X衍射精细结构数据表明:在～270 K,D-缬氨酸单晶分子内N―H…O氢键中,N―H、H…O的键长及键角∠N―H…O都发生波动起伏而不可测,但N―H…O总键长变化稳定可测.说明没有发生构型相变为L-缬氨酸.根据D-和L-缬氨酸单晶中,NH3→CO2顺时针和逆时针的相反走向及D-,L-和DL-缬氨酸晶体旋光角的测定,在270-290 K可以观察到晶格分子间N+H…O-氢键电子库珀对的自旋流超导相变.

橡胶塑料专用纳米CaCO_(3)的表面改性研究

以实验室自制纳米CaCO_(3)为原料、样品吸油值为主要考察指标,筛选并确定DL-苹果酸为较适宜的改性剂,考察并确定了较适宜的纳米CaCO_(3)改性工艺条件:DL-苹果酸质量分数为1.5%、改性温度为60℃、固液比为8∶100、改性时间为120 min。优化改性条件下所制备改性纳米CaCO_(3)样品的性能指标符合橡胶塑料专用纳米CaCO_(3)国家标准(Ⅰ型)样品的指标要求。样品FE-SEM、XRD和FT-IR分析结果表明,改性前后纳米CaCO_(3)样品均为方解石型和球霰石型的混合相;改性前后样品分散性较好,粒径约为20~50 nm;DL-苹果酸主要通过在纳米CaCO_(3)颗粒表面附着进行改性,降低样品的吸油值,同时改变样品不同晶型间的含量。

dl-吴茱萸碱的化学合成

综合国内外大量文献,简单介绍dl-吴茱萸碱的理化性质、用途和化学合成工艺路线,并提出了一条以色胺和N-甲基邻氨基苯甲酸为起始原料的适合工业生产的简便适用经济的化学合成方法。该工艺具有原料易得、反应条件不太苛刻、收率高等特点,产品质量已得到国内外用户认可。

丁苯酞软胶囊治疗急性期后循环缺血的疗效

目的观察dl-3-正丁基苯酞软胶囊治疗急性期轻中度后循环缺血的疗效。方法入选86例患者,随机分为治疗组43例和对照组43例。对照组给予长春西汀注射液静滴,每日1次;治疗组在此基础上给予丁苯酞软胶囊口服,疗程为2周。评价两组患者在治疗前及治疗第7天、第14天的神经功能。结果两组患者治疗前的一般情况及美国国立卫生研究院脑卒中量表(NIHSS)、临床神经功能缺损程度评分差异均无统计学意义,具有可比性;治疗第7天和第14天的NIHSS评分和临床神经功能缺损程度评分较治疗前均显著降低(P<0.05)。结论dl-3-正丁基苯酞软胶囊对轻中度后循环缺血急性期的治疗具有显著效果。

dl-3-正丁基苯酞对脑损伤大鼠的神经保护作用的实验研究

目的:研究dl-3-正丁基苯酞(NBP)对脑损伤大鼠的神经保护作用。方法:将100只7周龄清洁级雄性Sprague-Dawley(SD)大鼠随机分成5组,分别为假手术组、模型组、NBP低、中和高剂量组,每组20只。使用控制性皮层撞击损伤建立中型大鼠颅脑损伤模型。将NBP溶解在大豆油中,NBP低、中和高剂量组分别按照每天20、40和80 mg/kg的剂量灌胃,假手术组和模型组灌胃等体积的大豆油,共给药2周。采用改良神经功能缺损评分(m NSS)对大鼠的神经系统状况进行评价。检测各组大鼠治疗后的脑组织含水量以及脑组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平。TUNEL方法鉴定细胞的凋亡。通过RT-PCR、Western blot或免疫组化检测脑组织中Nrf2、NQO-1、HO-1、ApoJ、MMP9、AQP4、Caspase-3和AKT的表达。结果:NBP治疗2周后,NBP低、中和高剂量组大鼠的m NSS评分和神经元凋亡率以剂量依赖性方式显著降低(P<0.05)。与模型组比较,NBP低、中和高剂量组大鼠的脑含水量均显著降低(P<0.05)。与模型组比较,NBP低、中和高剂量组大鼠的MDA显著降低,而SOD和GSH-Px显著升高(P<0.05)。与模型组比较,NBP低、中和高剂量组大鼠的细胞核Nrf2显著升高,而细胞质Nrf2显著降低(P<0.05)。与模型组比较,NBP低、中和高剂量组大鼠的NQO-1和HO-1蛋白表达水平显著升高(P<0.05)。与模型组比较,NBP低、中和高剂量组大鼠的AQP4、MMP-9、ApoJ和Caspase-3的m RNA和蛋白表达水平均显著降低,而AKT显著升高(P<0.05)。结论:NBP对创伤性颅脑外伤大鼠具有一定的神经保护作用。