Effects of a Korean herbal formulation, Silsosangami, consisting of seven medicinal herbs, and its seven herbs on endotoxin-induced experimental thrombosis in rats

A traditional Korean medicine, Silsosangami (SSG), consisting of seven different herbs of Typhae Pollen, Pteropi Faeces, Paeoniae Radicis rubra, Cnidii Rhizoma, Persicae Semen, Carthami Flos and Curcumae Tuber, has been reported to have a hypolipidemic effect in human subjects. In the present study, the inhibitory effects of SSG on a thrombosis in rats, induced by endotoxin treatment were examined. The anti-thrombic properties of SSG were also investigated with respect to blood parameters. The extracts of SSG and five of the seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited both endotoxin-induced disseminated intravascular coagulation (DIC) and thrombosis in rats. The extract also inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and the endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In conclusion, the artificially induced, protective effects of SSG on ischemic infarction might be related to their inhibitory effects on DIC, platelet coagulation and thrombotic action.     

天麻糖蛋白的抗凝与抗栓作用

目的：观察天麻糖蛋白(PGE2-1)的抗血凝与抗血栓作用。方法：玻片法、减尾法检测小鼠凝血时间(CT)和出血时间(BT)；减尾测5 min后的出血量吸光度(A₅₄₀)；小鼠体内测定血浆复钙时间(RT)；ADP诱导血小板聚集(PAG)；试剂盒测定血浆凝血酶原时间(PT)、凝血酶时间(TT)、部分凝血活酶时间(APTT)；体外血栓仪测定大鼠体外形成血栓的长度、湿重、干重；实验性动静脉旁路血栓模型测定血栓的湿重及PGE2-1对其的抑制率。结果：60,120 mg·kg^-1的PGE2-1能显著延长小鼠的凝血时间、出血时间,增大出血量(A540)(P<0.05或P<0.01)。30,60,120 mg·kg^-1的PGE2-1能延长小鼠血浆复钙时间,降低血小板聚集率(P<0.05或P<0.01)。10,20,40 mg·mL^-1的PGE2-1能使TT和APTT显著延长(P<0.05或P<0.01),但对PT的影响无统计学意义。30,60,120 mg·kg^-1的PGE2-1能使小鼠消除血栓症状、恢复自主活动时间明显缩短(P<0.05或P<0.01)；使大鼠体外形成的血栓长度显著减短、湿重和干中显著减小(P<0.05或P<0.01)；极显著减小大鼠实验性动脉血栓的湿重(P<0.01),各药物组抑制率分别为32.5%,49.0%和61.5%。结论：PGE2-1具有显著的抗凝、抗栓作用,可能为天麻提取物在抗栓方面的主要成分。     

A snake venom metalloproteinase, kistomin, cleaves platelet glycoprotein VI and impairs platelet functions

Summary.  Background and objectives:  Injuries to the vessel wall and subsequent exposure of the matrix of the subendothelial layer resulted in thrombus formation. Platelet glycoprotein (GP) Ib and VI play a crucial role in matrix-induced activation and aggregation of platelets. Methods and results:  In the present study, we reported that the GPIb-cleaving snake venom metalloproteinase (SVMP), kistomin, inhibited collagen-induced platelet aggregation. Moreover, kistomin inhibited platelet aggregation induced by convulxin (CVX, a GPVI agonist) and a GPVI-specific antibody in a concentration and time-dependent manner. Kistomin treatment decreased platelet GPVI but not integrin α2β1 and αIIbβ3, accompanied with the formation of GPVI cleavage fragments, as determined by flow cytometric and Western blot analyses. In addition, intact platelet GPVI and recombinant GPVI were digested by kistomin to release 25- and 35-kDa fragments, suggesting that kistomin cleaved GPVI near the mucin-like region. We designed four synthetic peptides ranging from Leu¹⁸⁰ to Asn²⁴⁹ as the substrates for kistomin and found that kistomin cleaved these synthetic peptides at FSE²⁰⁵/A²⁰⁶TA and NKV²¹⁸/F²¹⁹TT, as analyzed by MALDI-TOF-MS. In addition, GPVI-specific antibody-induced tyrosine kinase phosphorylation in platelets was reduced after kistomin pretreatment, and platelet adhesion to collagen but not to fibrinogen was attenuated by kistomin. Conclusions:  We provided here the first evidence that a P-I snake venom metalloproteinase, kistomin, inhibits the interaction between collagen and platelet GPVI through its proteolytic activity on GPVI, thus providing an alternative strategy for developing new anti-thrombotic agents.     

122个中草药复方体外抗栓溶栓作用的研究

通过１２２个中草药复方的体外抗栓和溶栓实验，结果提示：抗栓率明显高子阿斯匹林（ＡＳＡ）抗栓率（６１．５３％）的复方有７个（Ｐ＜０．０５—０．０１），类似于ＡＳＡ的５７个（Ｐ＞０．０５）；溶栓率非常明显，高于尿激酶１（ＵＫ１）溶栓率（９１．２８％）的复方有４个（〈０．０１），类似于ＵＫｌ的４８个（Ｐ〉０．０５），类似于ＵＫ２溶栓率（９９．８３％）的复方４０个，表明从中草药复方中开发副作用小，又有抗栓、溶桂作用的天然药物大有潜力。本研究也发现，在抗栓和溶栓方面，部分中草药复方优子单方（Ｐ〈０．０５），值得进一步探讨。     

博洛克治疗急性脑梗塞223例疗效观察

采用随机抽样双盲法应用博洛克治疗223例急性脑梗塞患者,总有效率为93.72%,显效率70.40%,治疗组纤维蛋白原、优球蛋白溶解时间、全血粘度、血浆粘度、血小板聚集功能均有下降,未发现任何毒副作用.     

阿魏酸钠的心脑血管药理作用研究进展

阿魏酸钠是传统活血化瘀中药当归和川芎提取物中主要活性成分阿魏酸的钠盐,来源非常丰富,具有多种药理活性,且不良反应少、安全性高,于1990年首次被批准用于临床,是我国完全自主研发的心脑血管药物。阿魏酸钠在心脑血管疾病方面具有广泛的效用,在治疗呼吸系统疾病、糖尿病及其并发症,保护肝脏、肾脏等方面也较为有效。对近30年来阿魏酸钠在心血管疾病方面的药理作用及研究现状进行综述,重点阐述其在抗血栓、抑制血小板聚集、血管保护及抗氧化等方面的作用,以期为阿魏酸钠的临床应用提供理论依据。     

香椿子正丁醇提取物的抗血栓作用及其作用机制

目的：研究香椿子正丁醇提取物的抗血栓作用及其机制。方法：制作大鼠静脉血栓模型测定静脉血栓的湿质量、干质量及血栓抑制率检测香椿子正丁醇提取物对体内静脉血栓形成的抑制作用；用流式细胞仪的方法检测香椿子正丁醇提取物对凝血酶引起的血小板细胞内钙离子浓度上升的抑制作用和对血小板膜GPⅡh／Ⅲa受体表达的拮抗作用，了解香椿子正丁醇提取物抗血栓作用的机制。结果：预先给予香椿子正丁醇提取物5、10、20ms／ks，能显著降低大鼠静脉血栓的湿质量和干质量；在体外实验中，药物0．12、0．24、0．48ms／na可剂量依赖性地抑制凝血酶诱导的血小板内游离钙离子浓度的升高，尤其0．24mg／ml和0．48ms／ml组的作用更为明显；在3．84ms／ml剂量时，能降低血小板膜GPⅡb／Ⅲa受体的表达。     

丰城鸡血藤总黄酮抗血小板聚集及抗血栓作用研究

目的 研究丰城鸡血藤总黄酮对实验性大鼠血小板聚集和血栓形成的影响。方法 以二磷酸腺苷(adenosine diphosphate,ADP)、胶原和凝血酶作诱导剂诱导大鼠血小板聚集,丰城鸡血藤总黄酮按25,50,100 mg·kg^-1的剂量灌胃给药,测定大鼠血小板聚集率,计算聚集抑制率;用血栓法测定大鼠血栓形成重量。结果 丰城鸡血藤总黄酮各剂量均能抑制ADP、胶原和凝血酶诱导的大鼠血小板聚集,并能减少血栓形成的重量。结论 丰城鸡血藤总黄酮具有明显的抗血小板聚集及抗血栓形成的作用。     

P6A和RGD杂交肽的构象研究

用Ｂｉｏｓｙｍ公司的Ｄｉｓｃｏｖｅｒ程序计算了Ｐ６Ａ－ＲＧＤＳ，Ｐ６Ａ－ＲＧＤＶ，Ｐ６Ａ－ＲＧＤＦ，ＱＰ６Ａ－ＲＧＤＳ，ＱＰ６Ａ－ＲＧＤＶ和ＱＰ６Ａ－ＲＧＤＦ６种九肽在真空中、水中和正辛醇中的优势构象对应的能量。发现优势构象的总能量水平能反映这些九肽与ＧＰⅡｂ／Ⅲａ受体结合的情况，从而为以ＧＰⅡｂ／ⅢＰａ受体为靶点的含ＲＧＤ多肽药物设计提供帮助。     

Synergistic antiplatelet and antithrombotic effects of a prostacyclin analogue (iloprost) combined with a thromboxane antagonist (sulotroban) in guinea pigs and rats

The stable PGI₂-analogue iloprost and the TXA₂-receptor antagonist sulotroban were investigated for possible cooperative effects on platelet function and experimental thrombus formation in guinea pigs and rats.

Iloprost and sulotroban inhibit intravascular platelet aggregation in guinea pigs and rats induced by the stable endoperoxide U 46.619 and collagen, with iloprost beeing the more potent and (for collagen) more efficacious drug. Combinations of both compounds show synergistic or additive effects on in vivo platelet function. Thrombus formation in rats induced by vascular damage is strongly reduced by combining doses of iloprost and sulotroban (BM 13.177) which given alone are ineffective.

These results suggest a cooperative enhancement of antiplatelet and antithrombotic effects for combinations of iloprost and sulotroban. In view of disadvantages of currently used platelet inhibitors this cooperativity may offer a new approach in anti-platelet therapy.