Tanshinone IIA ameliorates chronic arthritis in mice by modulating neutrophil activities

Rheumatoid arthritis (RA) is a chronic immune inflammatory disease mediated by the influx of immune cells into the synovial joint space. As Tanshinone IIA (TIIA) has potent anti‐oxidant and anti‐inflammatory activities, we used the adjuvant‐induced arthritis (AA) murine model of RA to investigate the impact of TIIA on RA and immune cell activation. The anti‐arthritic activity of TIIA was investigated in an adjuvant‐induced arthritis model of RA in mice. Myeloperoxidase and neutrophil elastase expression levels were assessed in ankle joints by immunohistochemistry analysis. Immune cell infiltration was evaluated in air pouch experiments. Proinflammatory cytokines expression levels were determined by quantitative real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assays. Neutrophil extracellular traps (NETs) were assessed by immunostaining and confocal microscopy. Treatment with TIIA alleviated cartilage erosion and neutrophil infiltration in the ankle joints of AA mice and reduced proinflammatory cytokine expression levels in sera. TIIA suppressed interleukin‐6 and tumour necrosis factor‐α expression and release in neutrophils and promoted neutrophil apoptosis. TIIA also inhibited the NET formation of neutrophils. Our findings demonstrated that TIIA can ameliorate RA effectively by targeting neutrophils, indicating that TIIA may act as a potential therapeutic for RA.     

丹参酮IIA通过调控自噬抑制乏氧诱导的肝内胆管细胞癌侵袭能力的研究

目的:探讨在乏氧状态下,丹参酮ⅡA对肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)自噬的调控,以及对侵袭能力的影响及其机制。方法:通过1%O_2培养建立肝内胆管细胞癌ICC-9810细胞乏氧状态,应用丹参酮ⅡA干预细胞后,通过划痕试验检测ICC-9810细胞迁移能力,趋化试验及侵袭试验检测细胞的趋化与侵袭能力;转染p GFP-LC3质粒后,应用荧光显微镜观察LC3融合蛋白及自噬小体在ICC-9810细胞中的表达情况,蛋白质印迹法检测ICC-9810细胞中的HIF-1α、自噬相关蛋白LC3Ⅱ/I和Beclin1表达差异。结果:在乏氧环境下,ICC-9810细胞运动能力增强(1.75±0.3)倍,趋化能力增加79.6%,侵袭力增强1.36倍,细胞自噬水平明显升高,丹参酮ⅡA干预后ICC-9810细胞自噬水平下调,HIF-1α、LC3Ⅱ/I和Beclin1蛋白表达水平分别降低3.9倍,2.4倍和1.1倍,侵袭能力下降4.7倍。结论:丹参酮ⅡA可以通过下调自噬,抑制肝内胆管癌细胞在乏氧条件下异常增高的侵袭力。     

丹参酮ⅡA对大鼠肾间质纤维化的抑制作用

目的：探讨丹参酮ⅡA对大鼠肾间质纤维化的作用及机制。方法：30只雄性SD大鼠随机分为假手术组、模型组和丹参酮ⅡA组。结扎大鼠单侧输尿管建立肾间质纤维化动物模型。丹参酮ⅡA经腹腔注射，剂量为1．5mg／（kg·d）。术后第10天取梗阻侧肾组织作HE、Masson染色，观察肾间质病理改变。免疫组化法检测肾组织转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）及Ⅰ型胶原的蛋白表达与定位。逆转录-聚合酶链反应（RT-PCR）检测三者的mRNA水平。结果：模型组术后第10天梗阻侧出现明显的肾间质纤维化，肾组织TGF-β1、α—SMA和Ⅰ型胶原的蛋白及mRNA表达显著增加（P〈0．01）。丹参酮ⅡA组肾间质纤维化程度减轻，肾组织TGF-β1、α—sMA及Ⅰ型胶原表达下调（P〈0．05）。结论：丹参酮ⅡA对大鼠肾间质纤维化有明显的抑制作用，其机制可能与下调TGF-β1表达，抑制成纤维细胞增殖和表型转化，减少胶原沉积有关。     

丹参酮对肥厚心肌L-型钙电流的影响

目的心肌肥厚是导致心力衰竭、心律失常和猝死的高危因素。丹参酮已被证实能够有效地拮抗心肌肥厚的发生,但是对于其能否改变肥厚心肌上存在的电生理异常尚不清楚。方法本实验拟通过膜片钳和胞内钙测定技术,观察比较丹参酮和卡托普利对“一肾一夹”手术导致的肥厚心肌细胞膜上动作电位时间、L型钙通道电流和胞内钙离子浓度的影响,来阐明丹参酮预防心脏肥厚发生心律失常可能的电生理基础。结果丹参酮可以显著的缩短肥厚心肌细胞中存在的动作电位时间延长(P<0.001)、降低膜电容和ICa,L峰值幅度(P<0.001),但不影响ICa,L密度,并能够显著减少胞内钙离子浓度。结论丹参酮能够在抗心肌肥厚的同时通过减少钙内流、缩短动作电位时间,起到预防心律失常的作用。     

Tanshinone IIA Ameliorates Trinitrobenzene Sulfonic Acid (TNBS)-Induced Murine Colitis

Inflammatory bowel diseases are characterized by proinflammatory cytokines, oxidative stress, and tissue damage. Recently, tanshinone had been shown to act as an antioxidant, and to have anti-inflammatory bioactivity. The study was carried out to investigate the effect of tanshinone IIA on the inflammatory response of experimental colitis. Murine colitis was induced by trinitrobenzene sulfonic acid (TNBS). Ten or 20 mg tanshinone IIA was administrated to mice 4 h before the induction of colitis, and repeated daily until the mice were sacrificed. Colonic inflammation was examined by histological analysis, myeloperoxidase (MPO) activity, and the production of proinflammatory cytokines in colonic tissue. Activation of nuclear factor-kappa B was identified by western blot and immunohistochemistry, and oxidative stress was shown by glutathione (GSH) level in tissue. The mice with colitis treated by tanshinone IIA showed less tissue damage, lower MPO activity, less production of TNF-α and IL-1β, a higher level of GSH in colonic tissue, and downregulated activation of nuclear factor-kappa B in lamina propria mononuclear cells, compared with those of the untreated colitis group. Our data indicates that tanshinone IIA inhibits inflammatory response of colitis by downregulating the production of proinflammatory cytokines, and attenuating oxidative stress, which suggests that tanshinone IIA may be a new potential management for inflammatory bowel diseases.     

丹参酮ⅡA磺酸钠对冠心病患者血液流变学的影响

目的 探讨丹参酮ⅡA磺酸钠注射液对冠心病患者血液流变学的影响.方法 将60例冠心病人随机分为两组,均常规以调酯、抗血小板聚集、控制血压和/或血糖等药物常规治疗,观察组（41例）在常规药物治疗基础上加用丹参酮ⅡA磺酸钠注射液治疗,每次50 mg静脉滴注,每天1次,14d为1个疗程,观察两组的血液指标.结果 观察组病人经治疗后血黏度明显降低,两组比较差异有显著性（P＜0.05）.结论 静脉滴注丹参酮ⅡA磺酸钠注射液可使冠心病人血液流变学指标好转.     

中药丹参有效成分——丹参酮ⅡA的新的全合成方法

中药丹参为活血化瘀药。近几十年来植化工作者从丹参中分离出许多有效成分,其中丹参酮ⅡA有较好的抗菌活性和心血管系统活性,已被制成磺酸钠盐而用于临床(丹参精注射液),对心绞痛治疗总有效率达85%。过去也曾有人进行过丹参酮ⅡA的全合成。Baillie等以7-甲氧基-1-四氢萘酮为原料经十二步反应,Kakisawa等以2,3,4-三甲氧基苯甲酰     

丹参酮有关化合物的合成

药理试验表明丹参酮IIA及隐丹参酮等有耐缺氧作用。丹参酮IIA等的耐缺氧作用,可能与其邻醌结构有关。我们合成了一些改变醌式结构的丹参酮类似物,经试验,它们的耐缺氧作用减弱。丹参酮IIA由于磺酸基的引入而成水溶性化合物,临床试验对冠心病有效。但存在一些缺点,为了寻找更好的水溶性的丹参酮类化合物,合成了若干丹参酮Ⅰ和IIA的Mannich碱,药理试验表明有较好的抑菌作用。有关心血管方面的药理将另文报道。     

Brdu和PCNA标记观察丹参酮对癌细胞增殖的影响

为了解丹参酮的抗癌作用并探索其机理，用丹参酮处理人肝癌细胞株和白血病细胞株，Ｂｒｄｕ掺入标记和ＰＣＮＡ免疫组化染色检测癌细胞增殖动力学指标。结果：丹参酮处理人肝癌细胞和白血病细胞株后，Ｂｒｄｕ标记率分别为８．９５％，１９．０１％，均显著低于对照组（２８．０％，２５．５７％，Ｐ＜０．０１）；ＰＣＮＡ阳性率分别为５７．０％，３０．３２％，均显著低于对照组（７４．３％，４７．０５％，Ｐ＜０．０１）。结果表明，Ｂｒｄｕ标记和ＰＣＮＡ检测在研究肿瘤细胞增殖及影响因素等方面有重要应用价值，丹参酮抑制癌细胞增殖与抑制癌细胞ＤＮＡ合成、ＰＣＮＡ表达及ＤＮＡ多聚酶δ活性等有关。