Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Research Progress on the Anti-Atherosclerotic Effect and Mechanism of Tetramethylpyrazine

Atherosclerosis is a chronic vascular disease and the most common pathological change of cardiovascular disease.Its pathogenesis is closely related to inflammation,oxidative stress,lipid accumulation,and calcinosis.Tetramethylpyrazine plays an anti-atherosclerotic role by regulating lipid metabolism,inhibiting foam cell formation,alleviating inflammation,inhibiting vascular calcification and abnormal platelet activation,and has a cardiovascular protective effect.Therefore,this paper summarized the research progress of the anti-atherosclerosis effect and mechanism of tetramethylpyrazine.

工程教育中心何以推动科教融合——荷兰4TU工程教育中心的探索性单案例研究

工程教育中心作为建立在大学或研究机构中的跨学科交叉合作平台,是连接科学研究与教育实践的纽带,在高质量工程人才培养中发挥着重要作用。荷兰4TU工程教育中心利用4所顶尖理工大学在工程学科和教育领域的独特优势,积极与研发单位、教育单位、企业部门合作,通过将前沿科学研究彻底融入工程课程设计、教学模式等多个方面,形成了独具一格的科教融合工程人才培养模式。文章从战略目标、组织架构、运行机制、质量保障4个维度详实分析了4TU工程教育中心推动科教融合的内在机制,总结归纳其在主题项目设置、教育共同体形成、课程体系迭代、创新网络构建、内外部质量保障等方面的核心特征,期望对我国科教融合的工程教育改革与建设有所启示。

沉默TUFM通过AMPK/mTOR信号通路调控线粒体自噬对肺源性心脏病模型大鼠肺动脉高压的影响

目的探讨线粒体翻译延伸因子Tu(TUFM)通过线粒体自噬促进肺动脉高压(PAH)血管重塑的作用机制。方法2022年1月—2023年6月于辽宁省人民医院中心实验室进行实验。将36只健康雄性Sprague-Dawley大鼠随机分为空白对照(Ctrl)组、模型(PAH)组、TUFM过表达(OE)组、OE阴性对照(OE-NC)组、短发夹RNA(Sh)敲除TUFM(Sh)组和Sh-NC阴性对照(Sh-NC)组,每组6只。除Ctrl组外,其余大鼠均一次性腹腔注射1%野百合碱(60 mg/kg)诱导心源性肺水肿PAH大鼠模型;大鼠肺动脉平滑肌细胞(PASMC)在低氧(3%O 2)条件下培养24 h模拟体内肺动脉高压微环境,分为常氧(Norm)组、低氧(Hyp)组、小干扰RNA(SiRNA)-1组、SiRNA-2组、Si-NC组、OE-NC组和OE组。右心导管插管和脉冲多普勒超声检测大鼠肺血流动力学;苏木素-伊红染色检测肺小动脉病理结构;免疫荧光共染检测TUFM组织定位;细胞计数法检测细胞增殖;透射电镜观察线粒体结构和自噬小体;蛋白免疫印迹检测TUFM、自噬、凋亡和磷酸腺苷活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果与Ctrl组比较,PAH组大鼠TUFM蛋白表达升高,且主要与PASMC标志物α平滑肌肌动蛋白(α-SMA)在肺小动脉内膜存在共定位,而与内皮细胞标志物CD31无共定位,肺动脉收缩压(PASP)升高,肺动脉血流加速时间(PAAT)缩短,远端肺小动脉管壁呈向心性增厚,管腔狭窄几乎堵塞,TUFM、苄氯素1重组蛋白(BECN1)、人微管相关蛋白轻链3(LC3)II/I和B淋巴细胞瘤2(Bcl2)蛋白表达升高,P62、Bcl2相关X蛋白(Bax)和凋亡酶激活因子(Apaf)蛋白表达降低(P<0.05);与PAH组比较,OE组PASP升高,PAAT缩短,肺小动脉管壁厚度升高,肺动脉TUFM、BECN1、LC3II/I和Bcl2表达升高,P62、Bax和Apaf表达降低(P<0.05);与PAH组比较,Sh组PASP降低,PAAT延长,肺小动脉管壁厚度和管腔狭窄度有所改善,TUFM、BECN1、LC3II/I和Bcl2表达降低,P62、Bax和Apaf表达升高(P<0.05)。与Norm组比较,Hyp组PASMC细胞TUFM蛋白表达升高;与Si-NC组细胞相比,SiRNA-1和SiRNA-2组P62、Bax蛋白表达升高,BECN1、LC3II/I、Bcl2、TUFM表达降低,线粒体结构完整,PASMC细胞增殖活性降低,细胞p-AMPK表达降低,p-mTOR表达升高(P<0.05);与OE-NC组比较,OE组细胞P62和Bax蛋白表达降低,BECN1、LC3II/I、Bcl2和TUFM表达升高,部分线粒体损伤崩解,嵴断裂消失,PASMC细胞增殖活性明显升高,细胞p-AMPK表达升高,p-mTOR表达降低(P<0.05)。结论沉默TUFM可通过激活AMPK/mTOR信号通路促进线粒体自噬加速PAH肺动脉平滑肌细胞凋亡。

秦川牛宰后成熟过程中线粒体翻译延长因子Tu与能量代谢的关联性分析

目的:线粒体翻译延长因子Tu(mitochondrial Tu translation elongation factor,TUFM)已被证明参与秦川牛宰后成熟过程中的细胞自噬活动,实验探究该过程中TUFM表达与能量代谢变化的关系。方法:以秦川牛背最长肌为研究对象,测定4℃不同成熟时间(0、2、12、24、48、96、144、192 h)TUFM表达量及含量、葡萄糖(glucose,GLU)、乳酸(lactic acid,LA)、腺苷三磷酸(adenosine triphosphate,ATP)、二磷酸腺苷(adenosine diphosphate,ADP)、单磷酸腺苷(adenosine monophosphate,AMP)6种物质含量以及乳酸脱氢酶(lactate dehydrogenase,LDH)、琥珀酸脱氢酶(succinate dehydrogenase,SDH)、磷酸丙糖异构酶(triose phosphate isomerase,TPI)、苹果酸脱氢酶(malate dehydrogenase,MDH)、细胞色素c氧化酶(cytochrome c oxidase,COX)5种酶活性的变化情况。结果:在秦川牛宰后成熟期间,GLU、ATP、ADP、AMP含量和LDH、SDH、TPI活性均呈下降趋势,TUFM表达量、MDH活性及LA和TUFM含量均呈先上升后下降趋势,COX活性呈先下降后上升再下降趋势。能量代谢各指标和TUFM蛋白主要在宰后初期发挥作用,对宰后初期及宰后中后期分别进行Pearson相关性分析,结果表明,在宰后初期牛背最长肌中TUFM表达量与MDH、LA呈极显著正相关(P<0.01),与ATP、ADP、AMP、LDH、SDH、TPI、COX、GLU呈极显著负相关(P<0.01)。在宰后中后期,TUFM表达与所有指标(GLU、LA、ATP、ADP、AMP、LDH、MDH、SDH、TPI、COX)均呈极显著正相关(P<0.01)。结论:在宰后初期TUFM表达量逐渐增加,可为肌肉细胞提供能量从而用于能量代谢途径,该过程可能是TUFM正向参与细胞自噬所致。在宰后中后期能量短缺时,TUFM可能抑制细胞自噬,优先将能量用于除细胞自噬外的其他重要途径(如能量代谢途径)以维持细胞稳态。综上,在宰后成熟过程中TUFM具有双重作用,可调节细胞自噬为能量代途径提供能量,有助于维持宰后能量代谢持续的时间。

异氟烷麻醉对小鼠自发肌电及TUS/TMAS诱发肌电的影响

经颅超声刺激(TUS)和经颅磁声耦合刺激(TMAS)调控运动皮层效果明显,但受限于清醒状态动物难以束缚,已有研究大多在麻醉状态下进行,对麻醉减弱调控效果的分析集中于中枢神经系统。本研究记录了异氟烷麻醉下24只小鼠的肢体自发肌电和TUS/TMAS诱发肌电,定量分析了麻醉对自发肌电和诱发肌电发放率、潜伏期、时长和幅值的影响。结果显示,随着异氟烷输出浓度从0.40%增加至0.75%,每周期内小鼠自发肌电频次减少约50%,肌电发放时长变短,呈抑制状态;TUS/TMAS诱发肌电的成功率分别降低约50%和70%、潜伏期均延长约0.1 s、时长分别缩短约0.3和0.5 s,表明TUS/TMAS对运动皮层的调控效果随麻醉程度的加深而减弱。肢体自发和诱发肌电在发放率和时长上存在关联性特征,提示麻醉状态下小鼠自发肌电抑制状态可能是刺激效果减弱的影响因素之一。

绵羊肺炎支原体EF-Tu蛋白的原核表达及多克隆抗体制备

[目的]克隆绵羊肺炎支原体(Mycoplasma ovipneumoniae,Mo)EF-Tu基因,原核表达获得EF-Tu蛋白,制备抗EF-Tu蛋白的兔源多克隆抗体,为研究肺炎支原体EF-Tu蛋白的结构和功能奠定基础。[方法]采用重叠延伸PCR方法将pET-28a-EF-Tu质粒中EF-Tu基因中间的TGA密码子突变为TGG,并对测序结果与其他支原体参考株进行相似性比对和遗传进化分析,利用在线软件对其推测的蛋白序列进行生物信息学分析。将突变后的重组质粒转化大肠杆菌BL21(DE3)感受态细胞进行原核表达,经SDS-PAGE和Western blotting鉴定,利用镍柱亲和层析法纯化,以纯化的EF-Tu融合蛋白免疫家兔制备多克隆抗体,采用间接ELISA和Western blotting检测多克隆抗体效价及免疫反应性。[结果]试验成功突变了EF-Tu基因中TGA位点,并构建了融合表达His标签pET-28a-EF-Tu′原核表达载体。生物信息学分析表明,克隆的EF-Tu基因与绵羊肺炎支原体MoGH3-3菌株相似性最高,亲缘关系最近;编码387个氨基酸,无N-糖基化位点和跨膜区域,存在10个丝氨酸、20个苏氨酸、4个酪氨酸磷酸化位点,二级结构由无规则卷曲(35.14%)、α-螺旋(26.87%)、延伸链(26.87%)及β-转角(11.11%)构成。SDS-PAGE和Western blotting结果显示,目的蛋白大小约为43 ku,蛋白纯化浓度为0.615 g/L。ELISA和Western blotting结果显示,制备的多克隆抗体效价可达1∶128 000,能够特异性识别EF-Tu融合蛋白,具有良好的免疫反应性。[结论]本研究成功突变了EF-Tu基因的TGA密码子,原核表达并纯化获得EF-Tu融合蛋白,制备其多克隆抗体效价为1∶128 000,为后续研究肺炎支原体EF-Tu蛋白结构和生物学功能及其疫苗研发提供了试验基础。

The water-soluble TF3 component from Eupolyphaga sinensis Walker promotes tibial fracture healing in rats by promoting osteoblast proliferation and angiogenesis

Objective To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

An Investigation of Moxibustion Treatment for Abscesses in the Song Dynasty:Focusing on the“Jiu Ai Tu”

Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its research object and systematically analyzes the external treatment methods for abscesses during the Song dynasty reflected in Jiu Ai Tu.By examining the understanding of abscesses during that period,the paper explores the level of development in external medicine techniques.By analyzing the medical awareness and behaviors of patients when facing such severe illnesses,it aims to explore the societal cognition and experiences regarding health and disease.The paper attempts to present the folk medical ecology of the Song dynasty represented by Jiu Ai Tu.

EXPERIMENTAL STUDY ON THE EFFECT OF ACUPUNCTURE ON TROPISM-DISTRIBUTION OF TETRAMETHYLPYRAZINE AND THE CONTENT OF cAMP IN ARTHRITIS RATS

Objective： To verify two hypotheses： 1 ） Acupuncture can increase the re-distribution of tetramethylpyrazine （ligustrazine） hydrochloride （TMPH） to the target organs in adjuvant arthritic rats. 2） Cyclic Adenosine-3＇, 5＇-menophesphete （cAMP） is one of the guidance cues involved in this event. Methods： A total of 40 Wistar rats were randomized into blank control （BC）, model （MO）, medication （ME）, Acupuncture （Acu） and Acu＋ ME groups, with 8 cases in each group. Arthritis model was established by subcutaneous injection of complete Freund＇ s adjuvant （0.1 mL） into the rat＇ s foot pad. Electrcacupuncture （ 15 Hz, 0.2-0.3V） was applied to bilateral “Daling”（大陵 PC 7）, “Taichong” （太冲 LR 3） and “Xiguan” （膝关 LR 7） for 20 min, and the contents of TMPH in the heart, liver, kidney and the foot （affected focus） tissues and the contents of cAMP in the heart and liver tissues were determined with high performance liquid chromatography and radioimmunoassay techniques respectively. Results： Oornpared with medication group, the TMPH contents in the heart, liver, kidney and the affected foot tissues in Acu-ME group was obviously higher （ P〈0.05, P〈0.01 ）. In comparison with ME and Acu groups, the cAMP contents in the heart and liver in Acu＋ ME group was also significantly higher （P〈 0.05, P 〈 0.01 ）. No significant differences were found between ME and Acu ＋ ME groups in TMPH content of kidney and between Acu＋ ME and BC groups in cAMP contents in both liver and heart tissues. Conclusion： Acupuncture may promote the target-tropism distribution of ligustrazine, and cAMP may play an important role in it.

INFLUENCE OF ACUPUNCTURE ON BRAIN-TAXIS OF TETRAMETHYLPYRAZINE IN ACUTE CEREBRAL INFARCTION RATS

Purpose: To observe the effect of acupuncture on the brain-taxis of tetramethylpyrazine (TMP) and to explore into the underlying mechanisms of combined action of acupuncture and medicine in the treatment of acute cerebral ischemia. Methods: 37 male Wistar rats were randomly divided into normal control group (n=10), sham-operation group (n=10), acute cerebral ischemia (ACI) + drug group (model group, n=8)and ACI+drug+acupuncture group (acupuncture group, n=9). Rat ACI model was established by using photochemical method. "Neiguan"(PC 6) and "Shuigou"(GV 26) were punctured and stimulated with both hand manipulation and electroacupuncture, 30 min and 16hrs after ACI. TMP was given to the rats of the later 2 groups using gastric perfusion method. High pressure chromatography (HPLC) was used to detect the target absorption level of TMP in the brain. Results: The content of TMP in the brain in acupuncture group was significantly higher than that in model group (P<0.01), suggesting that acupuncture can strengthen the brain-taxis of TMP in ACI rats, and combined administration of acupuncture and Chinese drug maybe work better for treatment of acute cerebral infarction. Conclusion: Acupuncture can strengthen the chemo-taxis of TMP to the brain in ACI rats.

Simultaneous Determination of Tetramethylpyrazine and Aspirin in a New Compound Formulation by Liquid Chromatography

Aim To establish a reversed-phase liquid chromatographic (LC) method forsimultaneous determination of tetramethylpyrazine (TMP) and aspirin in a new compound formulation.Methods Chromatographic separation of the two drugs was achieved on a Diamonsil C_(18) column, usinga binary mixture of methanol-1.5% acetic acid (35:65, V/V, pH = 3.1) as mobile phase at a flow rateof 1.0 mL·min^(-1). Results Separation was completed in less than 12 min. Benzoic acid was used asthe internal standard. Recoveries at levels corresponding to 80 % to 120 % of the label claim ofthe formulation ranged from 99.6 to 100.3 % for aspirin and from 99.9 to 101.3% for TMP. The linearrange was 12.6 - 150.9 μg·mL^(-1)(r= 0.9997, n = 5) for aspirin and 25.0- 300.0 μg·mL^(-1) (r =0.9999, n = 5) for TMP. Conclusion The method developed can be used for the simultaneousdetermination of TMP and aspirin in pharmaceutical preparations.

Tetramethylpyrazine在视网膜色素上皮细胞变性及脉络膜血流和RPE细胞氧化应激中的作用(英文)

目的:研究1%Tetramethylpyrazine(TMP)在视网膜色素上皮细胞(RPE)变性,脉络膜血流和RPE细胞氧化应激中的作用。方法:在碘酸钠诱导的大鼠RPE变性研究中,1%TMP滴眼液预先处理1wk,3次/d,1wk后予碘酸钠舌下静脉注射,在2wk和4wk末,视网膜电图(ERG)测量c波。色素微球体技术分析高眼压状态下TMP对脉络膜血流的影响。Methylthiazoltetrazolium(MTT)分析TMP在各种氧化应激中对RPE的保护作用。结果:碘酸钠注射后2wk,碘酸钠组ERG的c波下降至对照组的36%(P<0.01)。4wk后,碘酸钠组下降至对照组的46%(P<0.01),而1%TMP+碘酸钠组下降至对照组的77%(P<0.01)。与碘酸钠组比较,1%TMP+碘酸钠组控制了67%的c波下降(P<0.05)。在脉络膜血流的测量中,30,60,和120min的结果显示,TMP显著增加脉络膜血流。在氧化应激部分,不同浓度的TMP在各种氧化应激损伤中,对RPE都有各种程度的保护作用。结论:浓度为1%Tetramethylpyrazine可以显著保护碘酸钠和氧化应激诱导的RPE变性,增加脉络膜血流,并可能在AMD的治疗中发挥作用。

Intra-articular delivery of tetramethylpyrazine microspheres with enhanced articular cavity retention for treating osteoarthritis

Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine(TMP) is enhanced when combined with borneol(BN) in a microemulsionbased transdermal therapeutic system(ME-TTS). The formulation of the TMP and BN microemulsion(TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher( P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group( P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.

PROTECTIVE EFFECT OF TETRAMETHYLPYRAZINE ON LEARNING AND MEMORY FUNCTION IN D-GALACTOSE-LESIONED MICE

To explore the protective effect of tetramethylpyrazine (TMP) on the learning and memory function in D-galactose (D-gal)-lesioned mice. Methods C57BL/6 mice were injected (s.c.) 2% D-gal for 40 days (100 mg·kg-1·d-1). Normal saline, TMP, and Huper-zine A were respectively given by intragastric administration in different groups from the third week. Learning and memory ability was tested with Morris water maze for 5 days at the sixth week. After completion of behavioral test, the mice were sacrificed by decapitation. The brain was rapidly removed, and the cortex and hippocampus were separated. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the cortex were determined. At the same time, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor in the cortex, and Bmax and KD of N-methyl-D-aspartate (NMDA) receptor in the hippocampus were determined. Results In this model group, (1) The deficit of learning and memory ability, (2) elevated MDA content and lowered SOD activity, (3) decreased AChE activity and M-cholinergic receptor binding sites in the cortex, and (4) lowered NMDA receptor binding sites were observed in the hippocampus, as compared with the normal control. TMP could markedly (1) attenuate cognitive dysfunction, (2) lower MDA content and elevate SOD activity, (3) increase the activity of ChAT and AChE, and M-cholinergic receptor binding sites in the cortex in the mice treated with D-gal. NMDA receptor binding sites were also increased in the hippocampus in the treated mice. Conclusion TMP can significantly strengthen antioxidative function, improve central cholinergic system function, protect NMDA receptor activity, and thus enhance the learning and memory ability in D-gal-lesioned mice.

TU1无氧铜/316L不锈钢电子束焊接接头组织与性能

采用真空电子束焊分别对2mm、3mm、5mm不同厚度的TU1无氧铜板材和316L不锈钢板材进行异种材料焊接,并对焊接接头的显微组织和力学性能进行了研究。实验结果表明:焊缝区和热影响区呈现波浪形状,焊缝区存在不同程度的混合组织,接头母材区及热影响区的晶粒大小随铜钢板材厚度的增加而增加。TU1热影响区的晶粒明相比母材区,明显增大。焊缝区的硬度高于母材区。在电子束电流为10mA,加速电压为150kV,焊接速度为15mm/s的焊接参数下,2mm、3mm、5mm厚的接头抗拉强度分别是263MPa、174MPa、141MPa。2mm厚的拉伸式样断裂发生在TU1热影响区,而3mm和5mm厚拉伸式样断裂发生在焊缝处,即2mm厚的TU1无氧铜板材和316L不锈钢板材焊接接头抗拉性能最好。

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

Anti-inflammatory and profibrinolytic effect of tetramethylpyrazine in acute coronary syndromes

Background and Objectives Tetramethylpyrazine (TMP) is a herb used widely in Traditional Chinese Medicine (TCM) as an antianginal drug. The exact mechanism whereby TMP treat ischemic heart disease is still not fully understood. The purpose of this study is to examine the anti-inflammatory effect of TMP in patients with acute coronary syndromes (ACS). Methods Thirty-two patients with acute myocardial infarction or unstable angina were randomly assigned to TMP group or control group. All patients received the same standard treatment. Patients in TMP group received TMP 3mg/kg every 12 hours for 5 days. Plasma concentrations of high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and after 5 days of therapy. Results Both CRP and SAA concentrations increased significantly in control group (P<0.05) whilst in TMP group, only SAA had a significant increase (P<0.05); the absolute increase of CRP, SAA, and PAI-1 were significantly less in TMP group than in control group (P<0.05). Conclusion TMP has an anti-inflammatory and profibrinolytic effect in patients with ACS. These effects may contribute to the clinical benefits of TMP in ischemic heart disease.

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro

BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemotherapy is a widely used strategy in colon cancer clinical therapy.However,chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer,and thus novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay,and cell apoptosis and cell cycle were assessed by flow cytometry.RESULTS TMP significantly inhibited the proliferation of colon cancer cells in a dose-and time-dependent manner.In addition,flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase.TMP treatment caused early stage apoptosis in SW480 cells,whereas it caused late stage apoptosis in HCT116 cells.CONCLUSION Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose-and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase.Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.