基于TRPV1/TRPA1调控TLR/NLRP3通路探讨中医药干预动脉粥样硬化研究进展

动脉粥样硬化（AS）是一种脂质堆积、血管内皮功能障碍导致的慢性炎症性疾病,Toll样受体（TLR）/核转录因子-κB(NF-κB)通路与NOD样受体蛋白3(NLRP3)炎性小体通路在动脉粥样硬化的产生中发挥着重要的致炎作用,而瞬时受体电位香草酸亚型1(TRPV1)与瞬时受体电位锚蛋白1(TRPA1)在动脉粥样硬化的发生过程中发挥着重要的保护作用。作者对近10年国内外期刊发表的相关研究进行梳理,研究显示,TRPV1/TRPA1的激活可以通过多种途径激活内皮型一氧化氮合酶（eNOS）、抑制活性氧（ROS）、抑制胆固醇晶体（CC）的产生进而调控TLR/NF-κB与NLRP3炎性小体通路,抑制TLR/NLRP3介导的炎症反应。同时,中医药中多种单味药有效成分与方剂可有效激活TRPV1/TRPA1或其下游途径,其对动脉粥样硬化中TLR/NLRP3通路可能具有显著调控作用。该文进一步对已探明的方剂及中药单味药有效成分调控AS中TLR/NLRP3通路的机制进行梳理,将TRPV1/TRPA1调控TLR/NLRP3途径的机制与中药方剂与单体成分进行对应。为治疗动脉粥样硬化的中药药物相互作用机制提供新启发...     

2型糖尿病氧化应激与单味中药干预研究

2型糖尿病的主要病因是胰岛素抵抗及胰岛β细胞功能受损。氧化应激是机体促氧化物产生和清除之间出现失衡的一种状态,被认为是糖尿病发生发展的重要危险因素。在代谢过程中,高血糖、高血脂导致线粒体产生大量活性氧,其可损坏线粒体功能,引起氧化应激反应。氧化应激则通过抑制胰岛素分泌;促进β细胞凋亡;降低胰岛素基因表达水平;阻断胰岛素作用通路,导致胰岛素抵抗等方式诱导2型糖尿病的发生发展。文章从氧化应激诱导胰岛素抵抗和胰岛β细胞功能受损机制及单味中药干预抗氧化应激反应研究等3个角度进行综述,希望对2型糖尿病氧化应激发病机制有更完善的认识,并为抗氧化中草药的研究提供新思路。     

中药治疗巨噬细胞：针对动脉粥样硬化的一种独特策略

动脉粥样硬化是心血管疾病的主要原因,是全球死亡人数最多的疾病之一。巨噬细胞是动脉粥样硬化过程中的主要参与者,是药物抑制炎症和调节脂质代谢的靶标。在本文中主要综述了传统中药和它们的活性化合物在治疗动脉粥样硬化方面的作用和机制。     

中药基于线粒体功能防治阿霉素心脏毒性研究进展

阿霉素诱导的心脏毒性是临床常见的严重并发症。近年研究发现,中药针对改善线粒体功能以防治阿霉素诱导的心脏毒性方面不断取得新进展。目前国内外相关研究报道主要集中在动物实验方面,基于线粒体功能障碍与阿霉素心脏毒性的病理机制、干预措施仍是研究热点。中药及其有效成分主要通过减少活性氧产生和释放、调控氧化酶活性、介导信号因子表达以抑制氧化应激和炎症反应发生发展;促进心肌组织中的底物利用、激发ATP酶活性、改善脂质代谢和糖酵解紊乱以提高线粒体能量供给;推动钙离子流动转出、减少载体蛋白单向摄入、稳定膜电位转移、提高线粒体膜通透性以缓解细胞内钙负荷;介导线粒体动力学相关蛋白、转录因子、生长因子、信号通路等定位表达以增加线粒体融合与减少过度裂变,调节Bcl-2、Bax、半胱氨酸蛋白酶-3等基因和蛋白的表达以平衡细胞凋亡与自噬。线粒体内部各个生物过程交叉相连,共同维持心脏细胞的正常运转。中药成分丰富,靶点众多,中西医结合治疗为恢复线粒体功能、减轻阿霉素心脏毒性提供了关键方向。     

中药调控细胞色素C的研究进展

目前,心血管疾病、癌症、败血症、脑组织损伤、糖尿病和神经性的疾病在全球的发病率非常高,在这些疾病中细胞色素C（cytochrome C,Cyt-C）均表现出不同程度的代谢紊乱。许多中药提取物、有效部位和化学成分对这些疾病有良好的治疗作用和较小的副作用。中药主要是通过影响疾病相关组织或细胞线粒体内的Cyt-C的产生或释放,调控相应靶细胞的凋亡,进而防治相应的疾病。查阅近年来的相关文献报道,综述了通过调控线粒体通路Cyt-C实现治疗疾病的中药提取物、有效部位和化学成分,希望能提高对中药在防病治病中作用机制的认识。     

基于痰浊理论探讨线粒体自噬与动脉粥样硬化相关性

动脉粥样硬化(Atherosclerosis,AS)是多种心脑血管疾病发生的基础,我国在AS基础与临床方面取得了理想的成果,但在AS病因学的研究还有待进一步提高。研究显示,氧化应激反应与细胞凋亡能够促进动脉粥样硬化发生与发展,线粒体功能障碍可一定程度加重机体氧化应激反应及细胞凋亡速度,这对AS病变有一定影响,从而可调控AS性心血管疾病。线粒体自噬是经对损伤线粒体的自身消化维持细胞稳态,并促进细胞生存,还可以调节凋亡、坏死、衰老功能来决定细胞最终的命运,在急性缺血性心血管疾病中线粒体自噬的作用显著。中医学认为动脉粥样硬化的病理变化属本虚标实、虚实夹杂,和痰浊内阻相关性较大。受损线粒体产生有害物质及线粒体的凋亡在中医可定义为"内生痰浊"范畴,而这种清除损伤线粒体及受损的细胞器的线粒体自噬恰如我们中医祛痰的治法。本文就从痰浊理论探讨线粒体与动脉粥样硬化相关性进行分析,挖掘中医药防治AS的潜在可能具有非常大的研究潜力和应用价值。     

中药复方诱导肿瘤细胞凋亡研究进展

在当前肿瘤细胞凋亡研究大趋势下,近年来中医药深入分子生物学领域探究凋亡具体机制有众多实验研究。文章综述了近年来中药复方诱导恶性肿瘤细胞产生凋亡具体机制实验探究的理论成果。中药复方在多基因、多因素等多方面诱导肿瘤细胞发生凋亡,主要包括阻滞细胞分裂的周期,诱导凋亡和清除体内活性氧;增强或抑制基因的表达;激活凋亡过程中线粒体、内质网、死亡受体信号转导通路和caspase家族诱导的信号通路等,同时能抑制端粒酶的活性等。     

糖尿病周围神经病变细胞凋亡机制及中医药干预研究进展

糖尿病周围神经病变是糖尿病最常见的并发症之一，其发病率高，是糖尿病患者致残、致畸、致死的主要原因。目前糖尿病周围神经病变的发病机制尚未阐述清楚，可能与氧化应激、炎症反应、微循环功能障碍、代谢异常等相关。近年研究发现，周围神经细胞凋亡在糖尿病周围神经病变的发病机制中具有重要作用。目前常见的细胞凋亡途径有线粒体通路、死亡受体通路和内质网通路，三者共同调控机体的细胞凋亡过程。中医药在糖尿病周围神经病变的治疗中疗效明确，具有整体调节、多靶点、多途径的治疗优势。研究表明，中药活性成分及复方可通过调控周围神经细胞凋亡信号通路达到改善糖尿病周围神经病变的效果。随着研究的深入，细胞凋亡途径可能成为继氧化应激后抗糖尿病周围神经病变新药研究的又一潜在靶点。因此，本文即以细胞凋亡为切入点，结合三条细胞凋亡途径相关的信号通路，综述了近年来中药干预糖尿病周围神经病变的研究进展，为糖尿病周围神经病变的临床防治及新药研发提供参考。     

心肌细胞铁死亡的机制及中药的保护作用

铁死亡是一种新型的细胞程序性死亡方式，典型特征为铁超载和脂质过氧化。心血管疾病是多种因素所导致的心脏发生的缺血性或出血性疾病，主要包括心肌梗死、心力衰竭等。铁死亡参与心肌细胞的损伤过程，并在多种心血管疾病的病程中起着推动作用；其主要作用机制包括铁稳态的破坏、活性氧的产生、抗氧化体系的紊乱，线粒体膜损伤、内质网应激及抑癌基因p53、核因子E₂相关因子2（Nrf2）途径等。心肌损伤是众多心病患者的死亡原因之一而中药单体或是复方都在治疗铁死亡导致的心肌细胞损伤中表现出了良好的效果，包括黄芩苷通过胞内磷脂酰肌醇3-激酶/蛋白激酶B/内皮型一氧化氮合酶（PI3K/Akt/eNOS）通路保护心肌缺血再灌注（I/R）大鼠的心脏微血管内皮细胞、龙牙楤木皂苷通过核受体亚家族3C组成员1/p53/溶质载体家族7成员11（NR3C1/p53/SLC7A11）通路抑制心肌细胞铁死亡、心阳片通过调节磷酸化混合谱系酶3/c-Jun氨基末端激酶/p53（MLK3/JNK/p53）信号通路改善氧化应激等。探索铁死亡的机制和挖掘相关中药在心肌细胞损伤后发挥的保护作用具有重要意义。该文对铁死亡的机制及其与心肌细胞的关系、通过铁死亡通路治疗心血管疾病的中药单体和复方进行了综述；重点介绍了中药治疗的通路和发挥的效果，以期为中药对心血管疾病的治疗提供参     

基于整合药理学平台探究参苓白术散治疗2型糖尿病的物质基础和作用机制

目的:探究参苓白术散治疗2型糖尿病的"成分-靶点-疾病"相关关系。方法:利用中药整合药理学计算平台搜索参苓白术散中所有药物相关的活性成分及潜在靶点,并搜索2型糖尿病疾病靶标,二者进行富集分析。结果:参苓白术散有499个药物化学成分,药物之间可能有较强的协同作用,经过基因本体数据库和京都基因与基因组百科全书数据库富集结果显示,其化学成分对应的关键靶点定位于细胞质、线粒体、髓鞘等,参与调控腺嘌呤核苷三磷酸结合、蛋白激酶活性等1 481个生物过程、基因功能,并参与嘌呤代谢、核苷酸代谢、神经系统等179个相关通路来治疗2型糖尿病。结论:本研究通过中药整合药理学平台筛选出了参苓白术散的化学成分,并预测出其治疗2型糖尿病的作用靶点和相关通路,可能与糖脂代谢、能量代谢等密切相关,为阐明其抗2型糖尿病的分子机制奠定基础,对深入挖掘和开发经典名方参苓白术散具有重要意义。     

药食同源中药调控氧化应激防治冠心病的研究进展

冠状动脉粥样硬化的形成与氧化应激密不可分,过量的活性氧（reactive oxygen species,ROS）损害内皮细胞、血管,进而引起氧化和抗氧化功能的失衡,造成心肌缺氧、缺血等症状。在过去数十年中,中药中抗氧化成分已广泛应用于包括冠心病和高血压在内的心血管疾病的治疗,药食同源中药因其具有天然、健康、运用广泛等特点在医药和功能食品领域备受关注。综述了药食同源中药通过调节氧化应激相关指标及信号通路预防冠心病的作用机制,以期为冠状动脉粥样硬化的预防研究和研制具有预防冠心病的药食同源产品提供参考和借鉴。     

中药治疗心血管疾病中线粒体氧化应激损伤的研究

线粒体是真核细胞中最重要的细胞器之一,是除细胞核以外唯一含有遗传物质的细胞器。在有氧呼吸过程中线粒体或多或少会产生活性氧,而活性氧积聚过多则会导致线粒体功能紊乱,参与各种疾病的发生与发展。随着我国对中医药事业的大力支持与深入挖掘,发现大量中药的疗效机制或与线粒体相关。     

Silibinin protects rat pancreatic β‐cell through up‐regulation of estrogen receptors' signaling against amylin‐ or Aβ1–42‐induced reactive oxygen species/reactive nitrogen species generation

Amylin and amyloid‐β (Aβ) were found to induce reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat pancreatic β‐cell line, INS‐1 cells, leading to cell death. In this study, we report on reciprocal relationship between the expression of estrogen receptors (ERs) α and β (ERα and ERβ) and generation of ROS/RNS in amylin/Aβ_1–42‐treated INS‐1 cells. That is, pharmacological activation of ERs in INS‐1 cells significantly decreases ROS/RNS generation, but blockage of ERs increases ROS/RNS generation. Silibinin is a natural polyphenolic flavonoid isolated from milk thistle with phytoestrogen activities, also known as silybin. Treatment with silibinin down‐regulated ROS/RNS production induced by treatment with amylin/Aβ_1–42 in the cells. Silencing ERs expression with siRNAs targeting ERs showed that the protective effect of silibinin was markedly weakened, indicating that silibinin protection is largely attributed to activation of ERs' signaling. The binding of silibinin to ERs implies that the protective effect of silibinin on amylin/Aβ_1–42‐treated INS‐1 cells owes to down‐regulation of ROS/RNS through the activation of ERs phosphorylation. Amylin and Aβ_1–42 cotreatment enhanced furthermore ROS/RNS generation and cytotoxicity through further down‐regulation of ERs phosphorylation, and this was reversed by silibinin. Silibinin also protects INS‐1 cells from amylin and Aβ_1–42 cotreatment. These results indicate that protective effect of silibinin is mediated by enhancement of ERs phosphorylation that depresses ROS/RNS generation in amylin/Aβ_1–42‐treated INS‐1 cells.     

中药抑制NADPH氧化酶的研究进展

NADPH氧化酶异常激活生成过量活性氧介导的氧化损伤是多种疾病的病理机制,中药可通过抑制NADPH氧化酶而发挥抗氧化作用,减轻组织、血管、神经等损伤,对于动脉粥样硬化、缺血再灌注、高血压、高血糖等病理状态均有治疗意义。该文对具有NADPH氧化酶抑制作用的中药单体、复方与成药进行综述,以阐释、总结其可能的治疗意义与抑制作用的靶点机制。     

氧化应激与心血管疾病的关系研究进展

许多疾病如动脉粥样硬化、高血压、缺血性心脏病等可产生大量的活性氧,引起氧化应激,通过查阅近10年来中外文献研究发现,氧化应激在心血管疾病的发生发展过程中扮演了很重要的角色,而中药在抗氧化方面有其明显的疗效,为心血管疾病的预防和治疗提供了新的理论基础。     

Anticancer Potential of Myricanone,a Major Bioactive Component of Myrica cerifera: Novel Signaling Cascade for Accomplishing Apoptosis

Extract of Myrica cerifera bark has long been fruitfully used as a hepato-protective and anti-cancer drug in various complementary and alternative systems of medicine. Myricanone, its principal bioactive compound, had also been reported to have apoptosis-promoting ability. We evaluated its anti-cancer potential in vitro in HepG2 liver cancer cells and tried to understand the signal cascades involved in accomplishing apoptosis. Further, we ascertained by using a (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay (MTT) assay if it had cytotoxic effects on normal noncancerous liver cells (WRL-68). We deployed various tools and protocols, like phase contrast, scanning electron and fluorescence microscopies, performed an annexinV-FITC/PI assay and cell cycle analysis, and estimated the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization through flow cytometry. Further, analyses of cytochrome-c translocation and of HSP70 and caspase expressions were also done by using immunoblota and Enzyme linked immunosorbent assay (ELISA). Results revealed that myricanone induced apoptosis in HepG2 cells through generation of ROS, depolarization of the mitochondrial membrane, early release of cytochrome-c, down-regulation of HSP70 and activation of a caspase cascade; it had no, or insignificant, cytotoxic effects in WRL-68 cells in vitro and in mice in vivo. Thus, myricanone has great potential for use in formulating an effective drug against both hepatotoxicity and hepatocellular cancer.     

Total alkaloids of Sophora alopecuroides- and matrine-induced reactive oxygen species impair biofilm formation of Staphylococcus epidermidis and increase bacterial susceptibility to ciprofloxacin

ObjectiveTo investigate the mechanism by which total alkaloids of Sophora alopecuroides (TASA) and matrine (MT) impair biofilm to increase the susceptibility of Staphylococcus epidermidis (S. epidermidis) to ciprofloxacin.MethodsThe minimum biofilm inhibitory concentration (mBIC) was determined using a 2-fold dilution method. Structure of biofilm of S. epidermidis was examined by Confocal Laser Scanning Microscope (CLSM). The cellular reactive oxygen species (ROS) was determined using a DCFH-DA assay. The key factors related to the regulation of ROS were accessed using respective kits.ResultsTASA and MT were more beneficial to impair biofilm of S. epidermidis than ciprofloxacin (CIP) (P < 0.05). TASA and MT were not easily developed resistance to biofilm-producing S. epidermidis. The mBIC of CIP decreased by 2–6-fold following the treatment of sub-biofilm inhibitory concentration (sub-BIC) TASA and MT, whereas the mBIC of CIP increased by 2-fold following a treatment of sub-BIC CIP from the first to sixth generations. TASA and MT can improve the production of ROS in biofilm-producing S. epidermidis. The ROS content was decreased 23%−33% following the treatment of sub-mBIC CIP, whereas ROS content increased 7%−24% following treatment with TASA + CIP and MT + CIP combination from the first to sixth generations. Nitric oxide (NO) as a ROS, which was consistent with the previously confirmed relationship between ROS and drug resistance. Related regulatory factors-superoxide dismutase (SOD) and glutathione peroxidase (GSH) could synergistically maintain the redox balance in vivo.ConclusionTASA and MT enhanced reactive oxygen species to restore the susceptibility of S. epidermidis to ciprofloxacin.     

针灸防治心肌缺血再灌注损伤的线粒体通路研究进展

目的：探讨针灸防治心肌缺血再灌注损伤的线粒体细胞信号转导机制,为后续研究提供思路。方法:通过对近年来国内外有关线粒体心脏损伤的研究入手,分析针灸防治心肌缺血再灌注损伤的线粒体通路的研究进展。结果：研究多以大鼠为观察对象,主要从针刺改善线粒体功能,减少线粒体活性氧类（ROS）产生过量引起氧化应激,防止细胞内Ca2+超载和阻止线粒体通透性转换孔（mPTP）的开放等角度切入研究。结论：微小RNA(microRNA,miRNA)是基因网络、蛋白网络、代谢网络等的上游网络的调控环节。鉴于针灸作用的整体性特点,将miRNA引入针灸作用机制研究领域,可在基因或其他水平层面更好地揭示针灸作用机制。     

Anti inflammatory effect of natural honey on bovine thrombin‐induced oxidative burst in phagocytes

Thrombin, hyperglycemia and reactive oxygen species (ROS) have been discovered to play a pivotal role in the pathogenesis of cardiovascular disease (CVD). The aim of the study was to evaluate the direct effect of bovine thrombin (BTh) on ROS production by human neutrophils and rodent macrophages and to investigate the effect of honey on BTh‐induced ROS production from phagocytes. Professional phagocytes, i.e. neutrophils and macrophages, were stimulated by BTh and ROS production was measured in luminol/lucigenin enhanced chemiluminescence (CL) assays. In another experiment the effects of honey treatment on BTh‐induced ROS production by phagocytes was tested using a CL assay. The results indicate that BTh directly activates phagocytes. A significant generation of ROS was noted with the luminol/lucigenin enhanced chemiluminescence (CL) system. Honey treatment of phagocytes activated by bovine thrombin showed effective suppression of oxidative respiratory burst monitored by the CL assay. In conclusion, it can be assumed that this direct action of BTh on phagocytes causing ROS production might exaggerate the inflammatory response at the site of atheromatous plaques. The suppressive activity of honey towards thrombin‐induced ROS production by phagocytes could be beneficial in the interruption of the pathological progress of CVD and may play a cardioprotective role. Copyright © 2009 John Wiley & Sons, Ltd.