木犀草素对大鼠肺成纤维细胞增殖的作用

目的：研究木犀草素对乳鼠肺成纤维细胞增殖作用的影响。方法：取3d内出生的乳大鼠肺组织制备肺成纤维细胞,经纯化,接种于96孔培养板上,细胞分为正常对照组、醋酸泼尼松龙组、4×10^-4、4×10^-5、4×10^-6、4×10^-7mol·L^-14个不同浓度的木犀草素实验组,培养一段时间后,观察肺成纤维细胞的形态变化,测定肺成纤维细胞的生长曲线、增殖情况及细胞内超氧化物歧化酶（SOD）活力。结果：木犀草素浓度在4×10^-5、4×10^-6mol·L^-1时,可明显抑制肺成纤维细胞的生长和增殖,且细胞密度减小,细胞间隔变大,这种作用与药物浓度呈正相关性,且使肺成纤维细胞内蛋白质的含量减少,所有木犀草素给药组均可使肺成纤维细胞内SOD活力随剂量的增加而增加,且与正常对照组比较差异均有统计学意义。结论：木犀草素对大鼠肺成纤维细胞的增殖有抑制作用。     

木犀草素对大鼠主动脉的舒张作用及相关机制研究

 目的观察木犀草素的舒血管作用并探讨其作用机制。方法大鼠胸主动脉环张力测定法。结果在内皮完整及去内皮血管上,木犀草素均浓度(4.5～36 μmol·L^-1)依赖性地降低苯肾上腺素(PE)预收缩血管的张力,拮抗高钾引起的血管收缩;木犀草素使PE收缩曲线非平行右移,且使最大张力减小;L-NAME,propranolol对木犀草素的舒血管作用无显著影响;钾通道阻断剂TEA,4-AP,BaCl₂,5-HD均能显著减弱木犀草素的血管舒张作用;木犀草素可以显著地对抗无钙、无钾、无钙环境下渐复钙后由PE引起的血管收缩。结论木犀草素对血管的舒张作用表现为非内皮依赖性,其舒张作用与其直接抑制电压依从性钙通道、受体操纵性钙通道、细胞内钙释放,以及激活钾通道有关,而与α,β受体无关。     

木犀草素对银屑病抑制作用的研究

目的：探讨木犀草素对银屑病的抑制作用。方法：选取Balb/c小鼠30只,经咪喹莫特乳膏诱导制成银屑病样小鼠模型,苏木素-伊红（HE）染色分析皮损情况,酶联免疫吸附法、免疫组织化学法以及实时荧光定量聚合酶链式反应检测,分析木犀草素对银屑病的抑制机制。结果：木犀草素可改善银屑病红肿、鳞屑症状,降低皮肤失水率;经木犀草素干预同样可降低表皮厚度,但2 mg/mL、10 mg/mL浓度时其干预效果并不明显,50 mg/mL时皮肤表皮厚度低于模型组（P<0.05）;木犀草素10 mg/mL、50 mg/mL剂量组CD8+T细胞数量与模型组相比降低（P<0.05）。木犀草素干预后COX-2表达均与模型组相比明显降低（P<0.05）;木犀草素干预后IL-1β表达与模型组相比明显降低（P<0.05）,木犀草素10 mg/mL、50 mg/mL组IL-6表达与模型组相比明显降低（P<0.05）,木犀草素干预后IFN-γ表达与模型组相比明显降低（P<0.05）;木犀草素50 mg/mL时IFN-α/β mRNA合成量明显低于模型组（P<0.05）,木犀草素2 mg/...     

木犀草素对慢性肾衰竭大鼠的保护作用

目的:探讨木犀草素对慢性肾衰竭大鼠的保护作用.方法:采用腺嘌呤法对大鼠进行灌胃,连续30 d,建立大鼠慢性肾衰竭模型,对照组灌胃生理盐水.造模成功后将18只大鼠随机分为模型组、木犀草素高剂量组、木犀草素低剂量组,给予相应药物治疗15d.观察大鼠体态、毛发颜色及活动状况,ELISA法检测大鼠血清IL-6、TNF-α、BU...     

定痫方对戊四氮致痫大鼠模型海马神经元凋亡的影响

目的:观察戊四氮(PTZ)致痫大鼠海马神经元凋亡以及定痫方(AAP)的脑保护作用。方法:144只健康成年雄性Wistar大鼠随机分为对照组(CK组)、模型组(PTZ组)、定痫方大剂量组(AAPl组)、定痫方中剂量组(AAPm组)、定痫方小剂量组(AAPs组)和丙戊酸钠组(VPA组);每组24只。CK组和PTZ组分别给予生理盐水(4 ml/kg体质量.d)灌胃;定痛方各组分别给予定痫方大、中、小剂量(10.26 g/kg体质量、5.13 g/kg体质量、2.56 g/kg体质量)灌胃,VPA组给予丙戊酸钠(20 mg/kg.d)灌胃,每日1次;连续7 d。造模第1天,除CK组外,其余各组大鼠均腹腔注射戊四氮(PTZ)75 mg/kg体质量,观察记录大鼠行为学变化;于致痫后12 h、2 d、5 d、7 d相应时间点取材,制备脑标本,TUNEL检测海马神经元凋亡。结果:致痫后,除CK组外,其余各组海马区凋亡细胞增加;7 d,与PTZ组相比,AAPl组凋亡神经元阳性表达减少(P<0.05)。结论:凋亡参与致痫大鼠海马神经元死亡过程;定痫方能减少神经元凋亡,有神经保护作用。     

木犀草素对气道平滑肌细胞PI3 K/AKT通路的影响

目的观察木犀草素对小鼠气道平滑肌细胞增殖的影响及其与PI3 K/AKT通路的关系。方法分离并培养小鼠气道平滑肌细胞,α-actin免疫细胞化学染色鉴定,细胞分4组:对照组、PDGF组、PDGF+LUT组、LUT组,MTT法检测细胞增殖,Western Blot方法观察p-AKT表达的变化。结果 MTT检测发现,PDGF刺激气道平滑肌细胞后A490值较对照组明显增加(P<0.01),PDGF+LUT组A490值较PDGF组明显降低(P<0.05),LUT组A490值较对照组无明显变化;Western Blot发现,对照组p-AKT极低,PDGF组明显升高,PDGF+LUT组p-AKT较PDGF组降低。结论木犀草素能够通过抑制AKT的磷酸化水平,限制体外培养的气道平滑肌细胞的PI3 K/AKT通路激活,从而发挥抑制小鼠气道平滑肌增殖的作用。     

木犀草素对自发性高血压大鼠心肌组织的保护作用及NF-кB表达的影响

目的 通过对自发性高血压大鼠(SHR)血压、心肌组织内血管紧张素Ⅱ(AngⅡ)、内皮素1(ET-1)、一氧化氮(NO)浓度的检测,观察木犀草素对SHR心肌组织的保护作用及NF-кB表达的影响.方法 木犀草素低、中、高剂量组(Luteolin)(10,20,40 mg·kg<'-1>·d<'-1>)、卡托普利组(Captopril)(10 mg·kg<'-1>·d<'-1>)、模型阴性对照组(SHR),每组均8只,WKY大鼠8只做为正常对照组(WKY).灌胃8周后处死,检测其血压、心肌组织内ET-1及NO的浓度.采用Western blot法检测各组大鼠NF-кB p65蛋白表达情况.结果 木犀草素组低、中、高各剂量组和SHR组血压均高于WKY组,(P<0.05),各剂量组血压和Captopril组均低于SHR组,(P<0.05);给药后木犀草素各组心肌组织AngⅡ浓度、ET-1浓度较SHR组有显著下降(JP<0.05);心肌组织NO浓度较SHR组有显著升高,其差异有统计学意义(P<0.05);木犀草素各剂量组大鼠肺组织NF-кB p65蛋白表达明显低于模型对照组,差异均有统计学意义(P<0.05).结论 木犀草素能降低SHR大鼠血压,降低SHR大鼠心肌组织AngⅡ浓度和ET一1浓度;升高SHR大鼠心肌组织NO浓度,下调NF-кB p65蛋白的表达,从而产生保护心肌组织的作用.     

木犀草素对Aβ25-35损伤大鼠大脑微血管内皮细胞的保护作用

目的：研究木犀草素对Aβ25-35损伤大鼠大脑微血管内皮细胞的保护作用。方法：取3周龄Wistar大鼠制备大脑微血管内皮细胞,经过纯化,将细胞随机分为对照组、Aβ25-35损伤组、0.1、1.0及10μmol·L^-1不同浓度木犀草素实验组。采用MTS法、DCFH-DA染色法、SOD抑制率实验分别检测细胞存活率、细胞内活性氧含量及SOD活力。通过测定跨内皮细胞电阻抗、γ-谷氨酰转肽酶、碱性磷酸酶、TXA2及PGI2稳定代谢产物含量,观察微血管内皮细胞的功能及屏障特性。结果：木犀草素在0.1、1.0及10μmol·L^-1浓度时,可显著提高Aβ25-35作用后微血管内皮细胞存活率,并抑制细胞内活性氧产生,提高细胞内SOD活性。木犀草素亦可改善Aβ25-35作用后微血管内皮细胞的功能和屏障特性,表现为提高跨内皮细胞电阻抗,增加特征性酶含量,缓解TXA2及PGI2分泌失衡。结论：木犀草素对Aβ25-35损伤大鼠大脑微血管内皮细胞具有保护作用。     

中药复方对戊四氮致痫大鼠海马PKCα表达的干预作用

目的：观察戊四氮（PTZ）致痫大鼠海马神经元PKCα表达以及中药复方AAP的影响。方法：健康成年雄性Wistar大鼠,随机分为6组（n=24）：正常组（Normal）;②模型组（PTZ）;③中药大剂量组（AAPl）、④中药中剂量组（AAPm）、⑤中药小剂量组（AAPs）、⑥西药丙戊酸钠组（VPA）。复制戊四氮致痫大鼠模型,于致痫后12h、2天、5天、7天相应时间点取材,制备脑标本;免疫组化技术检测海马神经元PKCα表达。结果：正常组海马内PKCα阳性细胞表达较少;与正常组相比,模型组大鼠海马PKCα阳性细胞表达增加（P〈0.05）,差异显著;与模型组比较,中药AAPl、AAPm、AAPs各组PKCα阳性表达减少;7天,与模型组及VPA组相比,中药AAPl、AAPm、AAPs各组PKCα阳性表达降低,P〈0.05,差异显著。与PTZ组相比,VPA组海马CA3区PKCα阳性表达无显著差异（P〉0.05）。结论：PKCα在PTZ致痫大鼠海马中表达增强,可能在癫痫发作中起作用;中药复方AAP可降低致痫大鼠海马PKCα表达,有一定脑保护作用。     

依达拉奉对戊四氮致痫大鼠海马氨基酸递质通路的影响

目的探讨依达拉奉对戊四氮(PTZ)致痫大鼠海马氨基酸递质通路的影响。方法将36只成年Wistar大鼠随机分为正常对照组(NC组)、模型组(M组)和依达拉奉组(E组),观察3组大鼠的行为学和脑电图情况,应用免疫组织化学方法测定各组大鼠海马γ-氨基丁酸转运体和谷氨酰胺合成酶的含量。结果与M组相比,E组大鼠癫痫发作程度和脑电图改变以及海马γ-氨基丁酸转运体的含量均明显下降(P均<0.05),而谷氨酰胺合成酶的含量则明显升高(P<0.05)。结论依达拉奉可通过降低癫痫大鼠海马γ-氨基丁酸转运体含量和增强谷氨酰胺合成酶表达以达到对抗癫痫的效果。     

Protein kinase-based neural signaling pathways for ginsenosides: a retrospective review

Ginsenosides are the main active components of ginseng,which have been reported to target brain tissues and produce multiple neuroprotective effects.Ginsenosides have been shown to improve learning ability and memory in normal aged animals,and in an animal model of memory impairment.However,its underlying pharmacological mechanisms are very complicated,especially with regard to its effects on the activation of protein kinases in neurons.Previous reports have shown that some protein kinases may be affected by ginsenosides,including protein kinase C,calcium/calmodulin-dependent protein kinase Ⅱ,c-Jun-N terminal kinase,and protein tyrosine kinase.In this paper,protein kinases that may underlie the mechanisms of ginsenosides will be discussed.     

木樨草素对脂多糖诱导的小胶质细胞炎性反应的抑制作用

目的:以脂多糖(LPS)刺激小胶质细胞BV-2,体外模拟神经退行性疾病的炎症模型,探讨木樨草素的抗炎作用和机制。方法:采用LPS(0.1μg/mL)刺激小胶质细胞建立炎症模型,MTT法检测木樨草素对BV-2细胞的毒性作用;硝酸还原酶法检测木樨草素对LPS刺激BV-2细胞一氧化氮(NO)表达量的影响;一氧化氮合酶分型法检测木樨草素对LPS刺激BV-2细胞一氧化氮合酶(iNOS)活性的影响;Western Blot法检测木樨草素对LPS刺激BV-2细胞TLR4蛋白表达影响。结果:木樨草素低、中、高剂量及阳性药物能抑制LPS诱导的BV-2炎性反应。结论:木樨草素能够抑制小胶质细胞活化产生的炎症反应,其抗炎作用的机制可能是通过抑制TLR4信号通路而发挥效用。     

中药补脑止痫散对癫痫大鼠海马神经元凋亡基因Bax和Bcl-2表达的影响

目的 通过观察中药补脑止痫散对戊四氮化学点燃癫痫模型大鼠海马神经元凋亡基因Bax和Bcl-2表达的影响,探讨补脑止痫散治疗癫痫的相关机制.方法 从78只正常Wistar大鼠中随机选取10只列为正常组,剩余68只大鼠腹腔注射戊四氮制作癫痫点燃模型,再随机选取50只造模成功大鼠随机分为5组:模型组、丙戊酸钠组、补脑止痫散高剂量组、补脑止痫散中剂量组和补脑止痫散低剂量组,每组10只.用免疫组化法检测药物治疗各组大鼠与正常组和模型组比较海马中神经元凋亡基因Bax和Bcl-2蛋白表达的变化.结果 各治疗组大鼠海马Bax和Bcl-2蛋白阳性目标面密度值与模型组相比分别出现明显降低和升高(P<0.05),而补脑止痫散低剂量组大鼠海马Bax和Bcl-2蛋白阳性目标面密度值改变不明显(P>0.05),并且补脑止痫散高剂量组和中剂量组比较,以及此二组与丙戊酸钠组相比大鼠海马Bax和Bcl-2蛋白阳性目标面密度值改变均无明显差异(P>0.05).结论 中药补脑止痫散高、中剂量能调整癫痫患者海马神经元凋亡基因Bax和Bcl-2蛋白的表达,从而抑制癫痫发作.     

Combined antihypertensive effect of luteolin and buddleoside enriched extracts in spontaneously hypertensive rats

Ethnopharmacological relevance

Flos Chrysanthemi is used in a variety of diseases in traditional Chinese medicine including hypertension, and the total flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is known to modulate vascular functions and reduce the blood pressure. However, the active flavonoids and their synergistic effects on anti-hypertension are still unclear. To investigate the combined anti-hypertension effects of LUT and BUD enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti-hypertensive mechanism of LUT&BUD mixture.

Materials and methods

CODA Mouse & Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET, PGI₂ and TXB₂ were investigated by ELASA. Serum NO concentration was measured by the method of Nitric acid reductase.

Results

A single administration of LUT, BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and 15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30 days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group, respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels of ANG, ALD and ET, but increased serum NO concentration.

Conclusion

This study shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The effects of LBM on blood pressure are associated with RAAS and endothelial system. Thus, our experiments suggest that the combination of luteolin and buddleoside from Flos Chrysanthemi are potentially useful for the therapeutic treatments for hypertension.     

姜黄素对阿霉素肾病大鼠Notch信号通路相关蛋白的影响

目的:探讨姜黄素通过调控Notch信号通路相关蛋白表达延缓阿霉素肾病大鼠肾小球硬化进程的机制。方法:将60只SD雄性大鼠按随机数字表法分为六组,分别为空白组、模型组、对照组和姜黄素低、中、高剂量组。除空白组外,其余各组尾静脉注射阿霉素制备阿霉素肾病大鼠模型,造模成功后对照组以10 mg/kg盐酸贝那普利灌胃; 姜黄素低、中、高剂量组分别予50、100、200 mg/kg姜黄素灌胃; 空白组和模型组分别予等剂量0.9%氯化钠溶液灌胃,各组均灌胃6周。检测各组大鼠24 h尿蛋白定量、血生化指标,电镜观察大鼠肾脏病理结构改变,RT-PCR检测神经源性基因Notch同源蛋白1(Notch1)、转化生长因子β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)mRNA表达水平,免疫组化法检测Notch1、TGF-β1、MCP-1蛋白表达水平。结果:姜黄素可有效降低阿霉素肾病大鼠24 h尿蛋白定量、血肌酐和血尿素氮水平,改善肾脏病理结构,下调Notch1、TGF-β1、MCP-1 mRNA及蛋白在肾脏组织的表达,且呈剂量依赖性。结论:姜黄素可通过下调Notch信号通路相关蛋白的表达,抑制肾小球基底膜增厚和细胞外基质过度沉积,进而延缓肾小球硬化进程。     

石菖蒲挥发油对癫痫大鼠海马氨基酸含量的影响

目的 :研究石菖蒲萃取挥发油对癫痫大鼠海马内兴奋性与抑制性氨基酸含量的影响 ,探讨其抗癫痫的可能机制。方法 :用超临界CO₂ 萃取法 (SFE CO₂ )提取石菖蒲挥发油 ,脑室内注射海人酸 (KA)建立大鼠癫痫模型 ,观察经挥发油治疗后的癫痫大鼠海马氨基酸含量的变化。结果 :经石菖蒲挥发油 35mg·kg^-1腹腔注射后的KA大鼠海马的GABA含量明显升高 ,谷氨酸 (Glu)显著降低 (P<0.05 )。结论 :石菖蒲萃取挥发油可调节癫痫大鼠脑内的兴奋性与抑制性氨基酸的平衡 ,从而起到抗癫痫的作用。     

Effects of the flavone luteolin,isolated from Colchicum richii,on guinea-pig isolated smooth muscle and heart and on blood pressure and blood flow

The effects of the flavone luteolin, extracted from Colchicum richii, on guinea-pig isolated ileum, pulmonary artery, trachea, atrium, perfused heart, and on blood pressure and blood flow of anaesthetized guinea-pigs were studied. Luteolin (10^?5?3 × 10^?4 M) caused concentration-dependent relaxation of the tone of ileum, epinephrine-precontracted pulmonary artery and only mild relaxation of acetylcholine-precontracted trachea. These effects were not affected by pretreatment with 1 mM theophylline except in the ileum where theophylline shifted to the left the luteolin concentration-effect curve. Luteolin (3 × 10^?6?3 × 10^?4 M) caused an increase in the beating rate and the contractility of the spontaneously beating atrium and of the isolated perfused heart. Theophylline (1 mM) significantly inhibited the effects of luteolin on the atrium and the perfused heart. Luteolin, in doses of 0.3, 1.0, 1.5 and 5 mg/kg body weight had no effect on heart rate of anaesthetized guinea-pigs but caused depression of systolic and diastolic blood pressure except at the lowest dose used where there was a small increase in both parameters. Also, only the lowest dose (0.3 mg/kg) caused a small increase in blood flow. Larger doses of luteolin caused dose-related inhibition of blood flow. The effects of luteolin on blood pressure and blood flow were not affected by theophylline pretreatment (5 mg/kg). These observations suggest that the effects of luteolin may be tissue-specific and in the isolated heart they may be attributed to inhibition of cyclic AMP phosphodiesterase. The data further demonstrate that luteolin has potential cardiovascular effects that merit further investigation.     

Gastrodia elata modulated activator protein 1 via c-Jun N-terminal kinase signaling pathway in kainic acid-induced epilepsy in rats

Gastrodia elata (Orchidaceae) is a Chinese herb. Our previous study showed that Gastrodia elata is able to reduce epileptic seizures, oxygen free radicals, microglia activation, and apoptosis in kainic acid (KA)-treated rats. Activator protein 1 (AP-1) is involved in modulating the neuronal plasticity and apoptosis. Therefore, the aim of this study was to investigate the role of AP-1 in antiepileptic effect of Gastrodia elata. Gastrodia elata (0.5, 1.0g/kg) or valproic acid (VA, 250mg/kg) was administered orally in Sprague-Dawley rats for 1 week before and 2 weeks after intraperitoneal injection of KA. Protein levels of AP-1 were determined by measuring c-Jun and c-Fos proteins, and the mitogen-activated protein (MAP) kinases activations were determined by measuring the phosphorylations of extracellular signal-regulated kinases, p38, and c-Jun N-terminal kinases (JNKs) in the frontal cortex and the hippocampus of rat brain using Western blotting. These results indicated that pre-treatment with Gastrodia elata or VA activated JNK signal pathway and c-Jun expression, while post-treatment with Gastrodia elata or VA suppressed both the JNK signaling pathway and the c-Jun expression induced by KA. These findings suggested that Gastrodia elata regulated the AP-1 expression via the JNK signaling pathway in KA-induced epilepsy.     

木犀草素抑制类风湿关节炎大鼠NLRP3炎性小体活化增强关节骨保护作用研究

目的:考察木犀草素对胶原诱导型关节炎(CIA)大鼠NLRP3炎性小体调节作用,观察木犀草素对动物模型关节骨保护表现.方法:随机选取雌性SD大鼠分为空白组、模型组、木犀草素100mg/kg组(木犀草素组)、木犀草素50mg/kg+MCC950 20mg/kg组(联合给药组).除空白组外,其余各组构建关节炎模型.连续给药5...