Introduction:Atherosclerosis (AS) is driven by lipid accumulation, inflammation, and oxidative stress, leading to endothelial dysfunction and plaque formation. Emerging evidence indicates that iron overload and ferroptosis exacerbate these processes via enhanced lipid peroxidation and vascular injury. However, current Western medical strategies predominantly target lipid-lowering and inflammation, often overlooking iron dysregulation and ferroptotic pathways. Methods:We used ApoE-/- mice as an AS model and administered Tetramethylpyrazine (TMP), Paeoniflorin (PF), or their combination (TMP+PF). Serum lipids, oxidative stress biomarkers, iron metabolism indices, and ferroptosis-related markers were measured. Results:Both TMP and PF significantly reduced serum lipid levels and oxidative stress, normalized iron metabolism parameters, and suppressed ferroptosis-associated markers, indicating a protective effect against ferroptotic damage. Discussion:These findings suggest that TMP and PF mitigate AS by coordinately regulating oxidative stress, iron homeostasis, and ferroptosis. Their multi-targeted action may offer a complementary approach to conventional therapies, addressing the previously neglected mechanisms of iron-driven vascular pathology.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma. Methods: In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis. Results: In vivo experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that pazopanib suppressed transforming growth factor-beta 1 (TGF-beta 1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-beta 1/Smad and non-Smad signaling pathways during fibroblast activation. Conclusions: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-beta 1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-beta 1/Smad signal route and the TGF-beta 1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.

Anti-Müllerian hormone (AMH), is a TGF-β family autocrine hormone and cognate ligand for the type II AMH receptor (AMHR2). AMH signaling through AMHR2 plays an important role in fetal sexual development by inducing Müllerian duct regression in males. AMHR2 is aberrantly expressed in various human malignancies, including colon, testis, gastric, and ovarian cancers. Functionally, AMH has complex effects on cell cycle regulation; at physiological concentrations it promotes survival and chemoresistance of cell lines, whereas at supraphysiological concentrations it inhibits tumor cell viability. Like other TGF-β family members, binding of its target receptor effects changes in gene expression through activation of intracellular SMAD, NF-κB, and Akt signaling. We developed a fully human anti-AMHR2 monoclonal antibody, 7E1, from RenMab™ mice, which contain the full human immunoglobulin variable domain. 7E1 was found to contain a distinct binding epitope associated with efficient inhibition of AMH binding and signaling. 7E1 also displayed a better ADCC effect than the reference AMHR2 antibody. The in vivo half-life of 7E1 in AMHR2- and FcRn-humanized mice exceeded the reference antibody as well and is in a desirable range from a development perspective. To evaluate the safety and efficacy of 7E1 in vivo, we established syngeneic murine tumor models in AMHR2-humanized mice. We found that 7E1 monotherapy significantly inhibited tumor growth in a dose-dependent manner. Moreover, 7E1 was well tolerated in mice, and no adverse effects were observed even at extremely high doses (e.g. 100 mg/kg). Taken together, these data demonstrate that 7E1 is a novel anti-human AMHR2 blocking antibody with desirable pharmacokinetic and pharmacodynamic properties. 7E1 may potentially find broad application for a range of cancer indications in which AMH signaling is implicated. Citation Format: Yongfei Yang, Huilin Li, Hao Li, Yue Yan, Jianhui Li, Qingcong Lin, Huijun Yin, Xiangshan Zhou, Miao Zhang, Kunbao Wu, Leqiao Sun, Shan Zhong. 7E1, a novel blocking antibody targeting human anti-Müllerian-hormone-receptor II (AMHRII), elicits potent anti-tumor activity in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6343.

Abstract Anti-Müllerian hormone (AMH), is a TGF-β family autocrine hormone and cognate ligand for the type II AMH receptor (AMHR2). AMH signaling through AMHR2 plays an important role in fetal sexual development by inducing Müllerian duct regression in males. AMHR2 is aberrantly expressed in various human malignancies, including colon, testis, gastric, and ovarian cancers. Functionally, AMH has complex effects on cell cycle regulation; at physiological concentrations it promotes survival and chemoresistance of cell lines, whereas at supraphysiological concentrations it inhibits tumor cell viability. Like other TGF-β family members, binding of its target receptor effects changes in gene expression through activation of intracellular SMAD, NF-κB, and Akt signaling. We developed a fully human anti-AMHR2 monoclonal antibody, 7E1, from RenMab™ mice, which contain the full human immunoglobulin variable domain. 7E1 was found to contain a distinct binding epitope associated with efficient inhibition of AMH binding and signaling. 7E1 also displayed a better ADCC effect than the reference AMHR2 antibody. The in vivo half-life of 7E1 in AMHR2- and FcRn-humanized mice exceeded the reference antibody as well and is in a desirable range from a development perspective. To evaluate the safety and efficacy of 7E1 in vivo, we established syngeneic murine tumor models in AMHR2-humanized mice. We found that 7E1 monotherapy significantly inhibited tumor growth in a dose-dependent manner. Moreover, 7E1 was well tolerated in mice, and no adverse effects were observed even at extremely high doses (e.g. 100 mg/kg). Taken together, these data demonstrate that 7E1 is a novel anti-human AMHR2 blocking antibody with desirable pharmacokinetic and pharmacodynamic properties. 7E1 may potentially find broad application for a range of cancer indications in which AMH signaling is implicated. Citation Format: Yongfei Yang, Huilin Li, Hao Li, Yue Yan, Jianhui Li, Qingcong Lin, Huijun Yin, Xiangshan Zhou, Miao Zhang, Kunbao Wu, Leqiao Sun, Shan Zhong. 7E1, a novel blocking antibody targeting human anti-Müllerian-hormone-receptor II (AMHRII), elicits potent anti-tumor activity in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6343.

Background:Combination of Panax quinquefolium L and Salvia miltiorrhiza Bunge. (PS) has been widely used in the clinical treatment of ischemic heart disease. The purpose of this study was to explore the therapeutic effect and mechanism of PS on angiogenesis in rats after acute myocardial infarction (AMI).Methods:A rat model of AMI was established by ligating the left anterior descending (LAD) artery. The grouping and administration scheme were as follows: sham group, model group, PS low-dose (PS-L) group, PS high-dose (PS-H) group, PX-478 group and angiotensin converting enzyme inhibitor (ACEI) group. After 28 days of treatment, echocardiography, myocardial infarct size, some angiogenesis markers and the miR-155-5p/HIF-1α/VEGF axis were measured.Results:PS improved cardiac structure and function, reduced infarct size, and alleviated myocardial fibrosis and inflammatory cell infiltration in AMI rats. Mechanistically, PS enhanced the expression of HGF and bFGF in serum, increased the levels of MVD and CD31 in myocardial tissues, and inhibited the activation of the miR-155-5p/HIF-1α/VEGF pathway, which ultimately promoted angiogenesis. In addition, the regulatory effect of PS on angiogenesis was partly abolished by PX-478.Conclusion:PS increased the expression of MVD and CD31 in the myocardium and stimulated angiogenesis. The above effects of PS may be associated with the inhibition of the miR-155-5p/HIF-1α/VEGF axis.

Background: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. Methods: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. Results: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15–1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17–1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05–3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60–1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23–1.56), and in lowering down the TCM syndrome scores (SMD = –0.78, 95% CI –0.91 to –0.64), Minnesota Living with Heart Failure questionnaire (SMD = –1.01, 95% CI –1.56 to –0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28–0.89), B-type natriuretic peptide (SMD = –0.89, 95% CI –1.52 to –0.25), NT-proBNP (SMD = –2.07, 95% CI –3.34 to –0.08), and C-reactive protein (SMD = –2.04, 95% CI –4.12 to –0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E′ between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were “low” and “very low” according to the GRADE assessment. Conclusion: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

目的 基于中国中医科学院西苑医院经皮冠状动脉介入(PCI)术后病人的住院及门诊处方,挖掘中医药在真实世界中治疗PCI术后病人的用药规律.方法 采集2016年—2019年在中国中医科学院西苑医院行PCI术病人的术后处方,并使用频次统计、复杂网络分析、关联规则分析、聚类分析及因子分析对处方进行分析.结果 共纳入4536首研究方剂,涉及534味中药,这些中药多为补虚药、活血化瘀药、清热药;以甘、苦、温为主,入脾经及肝经.拓扑学分析得到生黄芪、丹参、当归、川芎、茯苓、陈皮6味核心药物.二项、三项关联中高关联度药物组合分别为3组、22组,系统聚类分析归为9大类,因子分析获得13个公因子.结论 现代中医药治疗PCI术后病人的整体原则以益气活血、化痰理气为主.

Background: Percutaneous coronary intervention (PCI), the most common method in treating coronary artery disease (CAD), has a variety of side effects. Yiqi Huoxue therapy (YQHX) can effectively alleviate the symptoms of patients and reduce the side effects. However, a reliable and systematic assessment of the methodologies is not available. Methods: Seven electronic databases were searched to identify randomized controlled trials of YQHX method for CAD after PCI. The quality assessment of the trials included was performed by employing the Cochrane Risk of Bias tool. Results: One thousand eight hundred sixty-eight patients from 23 randomized controlled trials were included in this review. The aggregated results showed that the experimental group got better effect in increasing ORR, TCMSRR, ECG, HDL-C, and in lowering the level of CRP, TC, and MACE in comparison with the control group. Conclusion: YQHX method is a valid complementary and alternative therapy in the management of CAD after PCI, and is an effective and safe therapy for CAD.

目的 探讨西洋参、丹参配伍对三氯化铁(FeCl3)诱导的大鼠颈动脉血栓形成的干预作用.方法 50只SD雄性大鼠随机分为假手术组(Sham组)、模型组(Model组)、阿司匹林组(ASA组),西洋参、丹参配伍水煎剂低剂量组(PSDL组)、高剂量组(PSDH组),每组10只,灌胃给药14 d后,应用含20μl 30％FeCl3的滤纸贴敷大鼠颈动脉诱导制备血栓形成模型;采用比浊法检测二磷酸腺苷(ADP)诱导的血小板聚集率,采用酶联免疫(ELISA)法检测血浆血栓素B2(TXB2)、6-酮前列环素F1α(6-K-PGF1α)和血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)水平,计算TXB2/6-K-PGF1α比值.结果 与Sham组比较,Model组大鼠血小板最大聚集率显著增高(P<0.05);与Model组比较,ASA组、PSDL组和PSDH组大鼠血小板最大聚集率均有不同程度降低,PSDL和PSDH组与Model组比较差异有统计学意义(P<0.05).ASA组、SPDL组和SPDH组血小板聚集抑制率分别为12.87％,15.92％和17.03％.与Sham组比较,Model组大鼠血浆中TXB2、TXB2/6-K-PGF1α比值、血浆GPⅡb/Ⅲa显著升高(P<0.01,P<0.05).与Model组比较,ASA组、PSDL组和PSDH组血浆TXB2、GPⅡb/Ⅲa水平均显著降低(P<0.05,P<0.01),TXB2/6-K-PGF1α虽有不同程度降低,但ASA组与Model组比较差异有统计学意义(P<0.01),PSDL组和PSDH组与Model组比较差异无统计学意义(P>0.05).结论 西洋参、丹参配伍具有通过抑制血小板活化聚集发挥防治大鼠颈动脉血栓形成的作用.

目的 基于数据挖掘分析心血管疾病气虚血瘀证方剂组方用药的配伍规律.方法 检索中国知网、维普资讯中文科技期刊数据库、中国生物医学文献数据库、万方医学数据库收录的治疗心血管疾病气虚血瘀证方剂,采用频次分析、系统聚类、关联规则分析、主成分分析等数据挖掘方法对方剂组方进行用药规律分析.结果 共纳入304首中药复方,涉及153味中药,出现频数最高的单味中药为黄芪(280次),其次为丹参(250次);聚类数量为3类时较好,常用药物包括红花、桃仁、当归、赤芍、黄芪、丹参、川芎、瓜蒌、薤白等,演化得到核心组合7个;关联分析显示,黄芪配伍丹参、红花配伍桃仁、黄芪配伍当归是常用的药对;主成分分析提取到30个主成分.结论 常见的心血管疾病气虚血瘀证方剂药类以活血化瘀、补气、理气、止血为主.

目的 基于网络药理学方法分析西洋参-丹参药对治疗冠心病的分子机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)检索西洋参、丹参的活性成分及其靶点,并在Uniport数据库标准化蛋白质靶点信息;通过Gencards、OMIM、TTD、DRUGBANK数据库获取冠心病相关靶点基因,筛选药物和疾病共同靶点,利用CytoScape3.7.0软件构建"成分-靶点"网络,筛选关键活性成分;通过STRING平台进行蛋白质相互作用分析,构建共同靶点PPI网络,筛选关键靶点基因;采用DAVID数据库对共同靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,通过CytoScape3.7.0软件构建"成分-靶点-通路"网络.结果 共筛选得到西洋参-丹参63个活性成分和153个潜在靶点,与1420个冠心病靶点相映射,得到72个共同靶点,富集分析得到GO分析结果578个、信号通路116条;西洋参-丹参的关键活性成分木犀草素、丹参酮ⅡA、β-谷甾醇、4-亚甲丹参新酮、丹参新醌D、二氢丹参内酯、2-异丙基-8-甲基菲-3,4-二酮、罂粟碱、鼠尾草酚酮和隐丹参酮主要通过调控信号传导与转录激活因子3(STAT3)、蛋白激酶1(AKT1)、肿瘤抑制蛋白53(TP53)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶14(MAPK14)、白细胞介素6(IL6)、血管内皮生长因子A(VEGFA)、人原癌基因c-Fos(FOS)、白细胞介素1β(IL1B)等相关靶点蛋白,干预机体的细胞增殖凋亡、炎症反应、信号转导、缺氧反应、基因表达、药物反应、对雌二醇的反应、蛋白质磷酸化等生物学过程,并可能通过HIF-1信号通路、PI3K/Akt信号通路、TNF信号通路、FoxO信号通路、MAPK信号通路、雌激素信号通路、T细胞受体信号通路等对冠心病的发生发展产生影响.结论 初步揭示了西洋参-丹参治疗冠心病多成分、多靶点、多通路的作用机制,为进一步临床开发利用提供理论基础和研究方向.

[目的]系统评价速效救心丸治疗急性冠状动脉综合征(ACS)的疗效和安全性.[方法]计算机检索MED-LINE、EMbase、Cochrane Library、中国知网数据库(CNKI)、维普数据库(VIP)和万方数据库(WanFang Data)等,纳入速效救心丸联合常规西药(治疗组)与单纯常规西药(对照组)对比治疗ACS的随机对照试验(RCT),检索时限均为从2009年1月1日—2019年7月15日.由两位评价者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析.[结果]最终纳入11个RCT,共1296例ACS患者.Meta分析结果显示:治疗组的临床终点事件发生率[RR=0.43,95％CI(0.29,0.64),P<0.0001]显著低于对照组,临床总有效率[RR=1.19,95％CI(1.12,1.26),P<0.00001]和心电图疗效[RR=1.29,95％CI(1.14,1.46),P<0.0001]均显著高于对照组,且差异有统计学意义;在C反应蛋白(CRP)[SMD=-0.55,95％CI(-1.09,-0.01),P=0.05]和不良反应发生率[RR=1.68,95％CI(0.09,30.38),P=0.73]方面,两组差异无统计学意义.[结论]当前证据显示,速效救心丸联合常规西药治疗能有效缓解ACS患者的临床症状、改善心电图疗效和降低临床终点事件的发生率,且安全性较好.受纳入研究质量和数量所限,上述结论仍需更多高质量的RCT加以验证.

目的 系统评价速效救心丸对比硝酸甘油治疗心绞痛急性发作的疗效和安全性.方法 计算机检索PubMed、EMbase、Web of SCI、the Cochrane Library、中国知网(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据资源系统(WanFang Data)、中国生物医学文献服务系统(SinoMed)等数据库,纳入速效救心丸对比硝酸甘油治疗心绞痛急性发作的随机对照试验(RCT),检索时限均为建库至2019年10月30日.由两位评价者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析.结果 纳入6项RCT,共651例心绞痛急性发作病人.Meta分析结果显示,试验组不良反应发生率低于对照组[RR=0.37,95％CI(0.20,0.69),P=0.002];两组心绞痛改善率[RR=1.00,95％CI(0.94,1.06),P=0.97]和心电图改善率[RR=0.94,95％CI(0.84,1.05),P=0.26]差异均无统计学意义.结论 当前证据表明,舌下含服速效救心丸或硝酸甘油片在心绞痛急性发作的治疗方面疗效均较好,但速效救心丸不良反应更少,安全性好.

目的 应用网络药理学分析丹参-黄芪-川芎配伍治疗冠心病心绞痛的作用机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)检索丹参、黄芪、川芎的靶点及活性成分,利用PharmgKb、TTD、DrugBank数据库获取与冠心病心绞痛相关的靶点基因,疾病/药物中的"成分靶点网络"采用Cytoscape 3.7.0软件构建,对关键活性组分进行筛选,并基于DAVID数据库分析共同靶点的京都基因与基因组百科全书(KEGG)富集通路.结果 筛选得出丹参-黄芪-川芎的活性组分共34个,直接作用靶点有13个,发现丹参-黄芪-川芎中的丹参新酮、槲皮素、丹参酮ⅡA、4-亚甲丹参新酮等重要活性成分,主要作用于ADRB1、ADRA2A、ADRA2B、ADRA2C等相关靶点蛋白的调节,通过对环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)信号通路、扩张型心肌病、神经活性配体-受体相互作用等信号通路的调控,发挥治疗冠心病心绞痛的作用.结论 初步揭示了丹参-黄芪-川芎改善冠心病心绞痛的作用机制,为后续基础研究以及更好地开发利用治疗冠心病心绞痛的相关中药成药提供理论依据和方向.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by the proliferation of myofibroblasts and deposition of extracellular matrix that results in irreversible distortion of the lung structure and the formation of focal fibrosis. The molecular mechanism of IPF is not fully understood, and there is no satisfactory treatment. However, most studies suggest that abnormal activation of transforming growth factor-β1 (TGF-β1) can promote fibroblast activation and epithelial to mesenchymal transition (EMT) to induce pulmonary fibrosis. Deglycosylated azithromycin (Deg-AZM) is a compound we previously obtained by removing glycosyls from azithromycin; it was demonstrated to exert little or no antibacterial effects. Here, we discovered a new function of Deg-AZM in pulmonary fibrosis. In vivo experiments showed that Deg-AZM could significantly reduce bleomycin-induced pulmonary fibrosis and restore respiratory function. Further study revealed the anti-inflammatory and antioxidant effects of Deg-AZM in vivo. In vitro experiments showed that Deg-AZM inhibited TGF-β1 signaling, weakened the activation and differentiation of lung fibroblasts, and inhibited TGF-β1-induced EMT in alveolar epithelial cells. In conclusion, our findings show that Deg-AZM exerts antifibrotic effects by inhibiting TGF-β1-induced myofibroblast activation and EMT.

目的 系统评价益气活血法治疗气虚血瘀型心房颤动的有效性和安全性.方法 计算机检索PubMed、EMbase、the Cochrane Library、Web of SCI、中国知网(CNKI)、万方数据资源系统(WanFang Data)、维普中文科技期刊全文数据库(VIP)、中国生物医学文献服务系统(SinoMed)等数据库,纳入益气活血中药合常规西药对比常规西药治疗心房颤动的临床随机对照试验(RCT)研究.由两位评价者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,应用RevMan 5.3软件进行Meta分析.结果 纳入17项RCT,共计1358例病人,Meta分析结果显示试验组在改善临床总有效率[RR=1.29,95％CI(1.20,1.39),P<0.05]、心电图疗效[RR=1.15,95％CI(1.02,1.28),P<0.05]、中医证候疗效[RR=1.27,95％CI(1.02,1.58),P<0.05]、中医证候积分[SMD=-1.80,95％CI(-2.82,0.77),P<0.05]、不良反应发生率[RR=0.40,95％CI(0.22,0.71),P<0.05]、血浆凝血酶原时间[SMD=2.99,95％CI(1.45,4.53),P<0.05]、活化部分凝血活酶时间[SMD=1.30,95％CI(0.67,1.94),P<0.05]及血浆纤维蛋白原[SMD=-2.70,95％CI(-4.21,-1.19),P<0.05]方面均优于对照组.结论 现有证据表明,在常规治疗基础上加上益气活血方药联合治疗心房颤动疗效更好,不良反应更少.

Ethnopharmacological relevance: Epimedium brevicornu Maxim as a Chinese herb, is recommended for the treatment of menopausal women with hypertension for 50 years. Icariin, as the main hydrophilic ingredient of Epimedium brevicornu Maxim, has been proven to be a plant sex hormone and lower blood pressure down. Here, we hypothesized that Icariin can regulate T cells differentiation which leads to the blood pressure decrease in castrated SHR rats. Aim of the study: The present study aimed to investigate the effects of the exogenous estrogen, androgen and Icariin on T-cell modulation in hypertension. Materials and methods: Two weeks after castration, both male and female SHR rats were given estradiol, testosterone, and Icariin intervention respectively. Body weight, blood pressure, and heart rate were tested weekly. After six weeks, proportion of T helper cells (Th), cytotoxic T cells (Tc), and regulatory T cells (Tregs) in both peripheral blood mononuclear cells (PBMCs) and splenocytes were tested by flowcytometry. Serum levels of estrogen, testosterone, AngII, TNF-alpha, IL-17 were tested by Elisa. Aortic arches were isolated for HE and Masson staining. The expressions of ER beta and AR in aorta were tested by Western-blot. Results: In both male and female SHR rats, we found that Icariin and estradiol lower blood pressure, but testosterone elevates blood pressure. Similar as testosterone, Icariin can attenuate Tc and Th proportions and elevate Tregs proportion in both peripheral blood and splenocyte in male SHR, which can be blunt by flutamide. Besides, Icariin performs similar function as estradiol that attenuates Tc proportions and elevates Tregs proportion in both peripheral blood and splenocytes in female SHR, which leads to the lower blood pressure and can be partly blunt by fulvestrant. Testosterone increases AngII and TNF-alpha levels in serum, leading to the higher blood pressure in both male and female SHR rats. Conclusion: These results verified that Icariin, as a plant sex hormone, can regulate T cells differentiation related to blood pressure decrease in SHR rats.

目的 研究肌动蛋白微丝(F-actin)体外刺激对血小板活化及血小板凝溶胶蛋白(gelsolin)浓度的影响,同时观察活血化瘀中药赤芍-川芎有效成分配伍的体外干预效应.方法 以人水洗血小板作为研究对象,分为低(2.5 μmol/L)、中(5μmol/L)、高(10 μmol/L)浓度F-actin组以及花生四烯酸(AA)、二磷酸腺苷(ADP)、凝血酶(th rombin)组,同时设中药F-actin(10 μmol/L)组和中药AA组使用芍药苷和川芎嗪联合干预,阿司匹林F-actin(10 μmol/L)组和阿司匹林AA组使用阿司匹林作为干预药物,另设对照组.采用流式细胞术检测血小板活化标志物CD62p的表达,使用血小板聚集仪测定最大血小板聚集率(PAR),采用ELISA法测定血小板gelsolin浓度.结果 与对照组比较,不同浓度F-actin及AA、ADP、thrombin均可引起PAR和CD62p表达升高(P＜0.01),且F-actin呈浓度依赖性.与AA组比较,低、中浓度F-actin组PAR与CD62p表达下降(P＜0.01),高浓度F-actin、ADP、thrombin组则无明显差异(P＞0.05).与对照组比较,中、高浓度F-actin组及AA组可诱导血小板gelsolin浓度增高(P＜0.05,P＜0.01).与AA组比较,低、中浓度F-actin以及ADP、thrombin组gelsolin浓度下降(P＜0.05).与高浓度F-actin组或AA组比较,川芎嗪和芍药苷与阿司匹林均可抑制F-actin和AA诱导的PAR和CD62p表达升高(P＜0.05).与高浓度F-actin组或AA组比较,川芎嗪和芍药苷可降低F-actin或AA诱导的gelsolin升高(P＜0.05),但阿司匹林无此效应(P＞0.05).结论 F-actin体外能够激活血小板导致其聚集、活化,10 μmol/L浓度能够诱导血小板大量分泌gelsolin,其效应与AA相似.血小板gelsolin可能是芍药苷和川芎嗪体外抗血小板聚集、活化的一个有效干预靶点.

Objective To observe the inhibition of thrombus formation by the effective part of Yiqi Huoxue compound and its mechanism using rat carotid thrombosis model. Methods The effective fractions of Salvia miltiorrhiza and American ginseng were extracted and purified, and then the ratio of raw drug amount was 3:1 to make Yiqihuoxue compound. Fifty SD male rats were randomly divided into sham operation group (S), model group (M), aspirin group (A), Yiqi Huoxue compound high (H) and low (L) dose groups. After 7 days of prophylaxis, sham operation group was given normal saline and the other groups were given thrombosis induced by FeCl3 on topical carotid artery. The rats were intragastrically administrated for 21 days and were detected by enzyme-linked immunosorbent assay (ELISA). The contents of TXB2, 6-K-PGF1α, AT-Ⅲ, PC, PLG, Endothelin-1 (ET-1) were measured. Result (1) Compared with S group, The platelet aggregation rate, TXB2 content, TXB2/6-K-PGF1α ratio, and ET-1 content were increased (P<0.05). The contents of 6-K-PGF1α, PC, AT-III, and PLG were decreased in group M (P<0.05). The difference was statistically significant. (2) Compared with group M, the contents of 6-K-PGF1α, PC, AT-III and PLG were increased (P<0.05). TXB2 content and TXB2/6-K-PGF1α ratio were significantly decreased in H and L groups (P<0.01). The ratio of TXB2, PLG and TXB2/6-K-PGF1α were significantly decreased (P<0.01), and the content of 6-K-PGF1α was significantly increased in group A (P<0.01). The difference was statistically significant. (3) Compared with group M, although the content of ET-1 in group H and L decreased, it did not show statistical difference. Conclusion Salvia miltiorrhiza and American ginseng are combined in a ratio of 3:1 for Yiqi Huoxue compound, which has an inhibitory effect on carotid artery thrombosis and may promote the elimination of thrombus. Its mechanism may be through the reduction of plasma TXB2, and the growth of 6-K-PGF1α. Its mechanism may be through the growth of PC, AT-Ⅲ, thus enhancing the activity of anticoagulant system. It is associated with increased PLG content and activity of the fibrinolytic system.

综述近年血小板活化相关信号通路的研究文献,回顾以血小板膜受体偶联蛋白系统为中心的血小板活化上游激动剂、下游活化标志物等信号通路分子,阐述多靶点、多通路导致血小板活化在血栓形成中的作用.