冠心病心绞痛患者血清CRP、尿酸、血脂、胆红素的临床意义及丹参酮ⅡA磺酸钠治疗效果的评价

目的观察冠心病心绞痛患者血清C反应蛋白(CRP)、尿酸(UA)、血脂、胆红素水平的变化,评价丹参酮ⅡA磺酸钠的临床疗效。方法选取79例心绞痛患者作为心绞痛组,另将同期经冠脉造影排除冠心病的患者55例作为对照组,比较2组患者血清CRP、UA、血脂、胆红素水平。将心绞痛患者随机分为2组,分别采用常规方法(常规治疗组)及加用丹参酮ⅡA磺酸钠(丹参酮组)治疗,比较2组患者临床疗效。结果与对照组比较,心绞痛组患者CRP、UA、低密度脂蛋白、总胆红素水平显著增高,高密度脂蛋白水平显著降低。丹参酮组患者显效率明显高于常规治疗组,治疗后丹参酮组患者UA、总胆固醇、甘油三酯水平均显著低于常规治疗组。结论血清CRP、UA、血脂、胆红素可能在心绞痛发病过程中起到重要作用,丹参酮ⅡA磺酸钠是治疗心绞痛有效药物。     

丹参酮ⅡA对急性胰腺炎相关性肺损伤的干预作用

[目的]研究丹参酮ⅡA对急性胰腺炎相关性肺损伤（APALI）的干预作用,并探讨其作用机制。[方法]SD大鼠随机分为3组：假手术（对照）组、APALI组及丹参酮ⅡA干预组,应用5%牛磺胆酸钠逆行胰胆管注射建立大鼠APALI动物模型,观察各组肺组织中肺脏湿干重比、髓过氧化物酶（MPO）的活性、肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）水平、细胞间黏附分子（CAM）的表达,同时比较各组肺组织损伤积分。[结果]与假手术对照组比较,APALI组肺组织肺脏湿干重比,MPO活性,TNF-αI、L-1β水平,ICAM的表达及肺组织病理损伤积分均显著增高（均P〈0.05）;丹参酮ⅡA干预组与APALI组相比,肺组织肺脏湿干重比,MPO活性,TNF-αI、L-1β水平,ICAM的表达及肺组织病理损伤积分均显著降低（均P〈0.05）;[结论]丹参酮ⅡA可以下调炎性因子的表达而减轻APALI的炎症反应。     

HPLC法同时测定乙肝益气解郁颗粒中的11种成分

目的建立HPLC法同时测定乙肝益气解郁颗粒中柴胡皂苷a、柚皮苷、芍药苷、毛蕊异黄酮苷、丹参酮IIA、桂皮醛、五味子醇甲、紫丁香苷、盐酸小檗碱、大黄酚和橙皮苷的含量,并采用主成分分析(PCA)法对其质量进行综合评价。方法采用HPLC法,色谱柱为Caprisil C18-AQ(250 mm×4.6 mm,5.0μm);流动相为0.1%磷酸水溶液-乙腈,梯度洗脱,体积流量0.8mL/min;柱温45℃。最后将定量结果与PCA法相结合对不同批次药物进行科学的质量评价分析。结果乙肝益气解郁颗粒中柴胡皂苷a、柚皮苷、芍药苷、毛蕊异黄酮苷、丹参酮IIA、桂皮醛、五味子醇甲、紫丁香苷、盐酸小檗碱、大黄酚和橙皮苷11种成分分别在1.6～80.0、14～700、10～500、1.6～80.0、1.6～80.0、2.4～120.0、1.2～60.0、1.2～60.0、8.0～400.0、2.0～100.0、2.0～100.0μg/m L线性关系良好;平均加样回收率分别为98.3%、99.2%、98.8%、99.3%、101.9%、97.5%、99.8%、101.7%、101.1%、102.5%、100.9%,RSD均2.0%;16批样品中11种有效成分的质量分数分别为0.233～0.322、3.007～3.142、2.201～2.273、0.320～0.355、0.317～0.399、0.451～0.523、0.265～0.297、0.209～0.226、1.848～1.873、0.380～0.425、0.615～0.647mg/g。结论实验建立的方法简便准确、重复性好,可用于乙肝益气解郁颗粒的质量控制,为乙肝益气解郁颗粒后续质量提高提供参考。     

丹参酮ⅡA抑制PI3K/AKT/NF-κB通路对炎性软骨细胞的保护作用

目的 研究丹参酮ⅡA对IL-1β诱导炎性软骨细胞的保护作用及PI3K/AKT/NF-κB通路的影响。方法 取SD大鼠10只,分离培养软骨细胞,分为正常组、丹参酮ⅡA（6.25,12.5,25,50 μmol·L^-1）剂量组,培养24 h后CCK8法检测软骨细胞增殖情况。另取软骨细胞分为正常组、IL-1β（10 ng·mL^-1）组和IL-1β+丹参酮ⅡA（6.25,12.5,25,50 μmol·L^-1）组共6组,IL-1β与丹参酮ⅡA共培养24 h。CCK8检测细胞增殖情况,ELISA法检测软骨细胞TNF-α、IL-6、PGE2、NO的含量水平。qRT-PCR和Western blotting检测软骨细胞iNOS、COX-2、collagen-Ⅱ、aggrecan、MMP-13、ADAMTS-5的mRNA和蛋白表达水平及PI3K/AKT/NF-κB通路蛋白表达水平。结果 对于正常软骨细胞,给予（12.5,25,50 μmol·L^-1）丹参酮ⅡA干预24 h可增加细胞增殖;对于IL-1β诱导的炎性软骨细胞,与IL-1β组相比,丹参酮ⅡA（25,50 μmol·L^-1）可增加细胞增殖（P<0.01）。IL-1β+丹参酮ⅡA（12.5 μmol·L^-1）组IL-6、PGE2、NO含量,COX-2、ADAMTS-5的mRNA表达及ADAMTS-5蛋白表达水平显著下降（P<0.05或P<0.01）,aggrecan蛋白表达水平上升（P<0.05）;IL-1β+丹参酮ⅡA（25,50 μmol·L^-1）组TNF-α、IL-6、PGE2、NO含量,iNOS、COX-2、MMP-13、ADAMTS-5的mRNA及蛋白表达,p-PI3K、p-AKT及p-P65蛋白表达水平显著下降（P<0.05或P<0.01）,collagen-II、aggrecan蛋白表达水平显著上升（P<0.05或P<0.01）。结论 丹参酮ⅡA可有效保护IL-1β诱导的炎性软骨细胞,可通过促进软骨细胞增殖,抑制炎症反应,抑制PI3K/AKT/NF-κB通路,发挥保护作用。     

Tanshinone IIA Induces Autophagic Cell Death via Activation of AMPK and ERK and Inhibition of mTOR and p70 S6K in KBM‐5 Leukemia Cells

Although tanshinone IIA (Tan IIA) from Salviae miltiorrhizae was known to induce apoptosis in various cancers, its underlying mechanism of autophagic cell death was not reported yet. Thus, in the present study, the molecular mechanism of autophagic cell death by Tan IIA was investigated in KBM‐5 leukemia cells. Tan IIA significantly increased the expression of microtubule‐associated protein light chain 3 (LC3) II as a hallmark of autophagy in western blotting and immunofluorescence staining. Tan IIA augmented the phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK) and attenuated the phosphorylation of mammalian target of rapamycin (mTOR) and p70 S6K in a dose‐dependent manner. Conversely, autophagy inhibitor 3‐methyladenine partly reversed the cytotoxicity and the phosphorylation of AMPK, mTOR and p70 S6K induced by Tan IIA in KBM‐5 leukemia cells. In addition, Tan IIA dramatically activated the extracellular signal regulated kinase (ERK) signaling pathway including Raf, ERK and p90 RSK in a dose‐dependent and time‐dependent manner. Consistently, ERK inhibitor PD184352 suppressed LC3‐II activation induced by Tan IIA, whereas PD184352 and PD98059 did not affect poly (ADP‐ribose) polymerase cleavage and sub‐G1 accumulation induced by Tan IIA in KBM‐5 leukemia cells. Furthermore, Tan IIA could induce autophagy via LC3‐II activation in various cancer cells such as prostate (PC‐3), multiple myeloma (U266), lung (NCI‐H460), and breast (MDA‐MB‐231) cells. Overall, these findings suggest that Tan IIA induces autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and p70 S6K in KBM‐5 cells as a potent natural compound for leukemia treatment. Copyright © 2013 John Wiley & Sons, Ltd.     

Sodium Tanshinone IIA Sulfonate Protects Mice From ConA-Induced Hepatitis via Inhibiting NF-κB and IFN-γ/STAT1 Pathways

INTRODUCTION: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury. RESULTS: C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappaB and IFN-gamma/STAT1. CONCLUSION: In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-kappaB and IFN-gamma/STAT1 signaling pathways.     

Effects of tanshinone II A on the myocardial hypertrophy signal transduction system protein kinase B in rats

Objective： To study the effect of tanshinone ⅡA on the cell signal transduction system protein kinase B （Akt） in rats with hypertrophy of the myocardium induced by partial constriction of the thoracic aorta. Methods： Rat models of myocardial hypertrophy were established by the thoracic aorta partial constriction method. Forty-eight rats were randomly divided into the sham-operative group, the model group, the valsartan treatment group, and the low-, medium-, and high-dose tanshinone treatment groups. The heart mass index （HMI）, left ventricular mass index （LVMI）, ejection fraction （EF）, left ventricular posterior wall （LVPW）, and interventricular septal thickness （IVS） were detected by high-frequency ultrasonography. The myocardial fiber diameter （MFD） was detected by HE staining, and the contents of p-Akt and p-Gsk3β in the myocardium were detected by Western blot. Results： Compared with the sham-operative group, the levels of HMI, LVMI, LVPW, IVS, and MFD were increased respectively in the other groups （P〈0.05）; the contents of p-Akt and p-Gsk3β were also increased in the other groups. Compared with the model group, the levels of HMI, LVMI, LVPW, IVS, and MFD were decreased respectively in all treatment groups （P〈0.05）; the contents of p-Akt and p-Gsk3β were decreased in all treatment groups as well. There was no significant difference, however, among the low-, medium-, and high-dose tanshinone treatment groups and the valsartan treatment group （P〉0.05）. Conclusion： Tanshinone HE A can prevent myocardial hypertrophy by its action on the protein kinase B （Akt） signaling pathway.     

叶酸修饰载丹参酮ⅡA纳米结构脂质载体的制备及其理化表征

[目的]制备载丹参酮ⅡA纳米结构脂质载体,将含有叶酸的PEG链配体修饰于制剂表面获得叶酸修饰载丹参酮ⅡA纳米结构脂质载体(FA-TanⅡA-NLC),使其具有肿瘤靶向作用,并对制剂进行理化表征。[方法]采用乳化蒸发-低温固化法制备制剂,以粒径、电位和包封率等为指标对制剂进行初步评价,采用透射电子显微镜(TEM)、差示扫描量热法(DSC)和X射线衍射法(XRD)对制剂进行进一步的表征。[结果]制备的叶酸修饰载丹参酮ⅡA纳米结构脂质载体(FA-TanⅡA-NLC)粒径为(19.14±0.43)nm,PDI为0.424±0.01,电位为(-11.67±0.25)mV,DSC以及XRD结果均表明丹参酮ⅡA以无定型形式被包载于纳米结构脂质载体中。[结论]本研究制得的FA-TanⅡA-NLC粒径分布均一,体系稳定,包封率高。