17-甲氧基-7-羟基-苯并呋喃查尔酮对大鼠凝血功能和血小板聚集的影响

目的:研究17-甲氧基-7-羟基-苯并呋喃查尔酮(YLSC)对体内外血小板聚集和凝血功能的影响.方法:将50只SD大鼠随机分为5组:对照组(含0.5％ DMSO的生理盐水),YLSC低、中、高剂量组(2.5,5,10 mg·kg-1),阳性药阿司匹林组(10 mg·kg-1).尾静脉注射相应药物1周后,腹主动脉采血,分别加入二磷酸腺苷(ADP)、胶原和花生四烯酸(AA)诱导血小板聚集,测定大鼠体内外血小板聚集率;同时观察YLSC对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响.结果:与对照组相比,YLSC能显著抑制ADP和胶原诱导的大鼠体内、外血小板最大聚集率(P＜0.05或P＜0.01),最大抑制率分别为38.4％,42.5％,对AA诱导的血小板聚集无明显抑制作用;YLSC能显著延长大鼠血浆TT,APTT(与对照组比较,P＜0.05或P＜0.01),对PT无显著影响.结论:YLSC具有对抗血小板聚集和抗凝血作用.     

芍药苷联合川芎嗪对肌动蛋白微丝诱导血小板活化及血小板凝溶胶蛋白水平的干预效应研究

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(2.5μmol/L)、中(5μmol/L)、高(10μmol/L)浓度F-actin组以及花生四烯酸(AA)、二磷酸腺苷(ADP)、凝血酶(thrombin)组,同时设中药F-actin(10μmol/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(10μmol/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,10μmol/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。     

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??OBJECTIVE To investigate the effect of potassiam 2-(1-hydroxypentyl)-benzoae(dl-PHPB) on platelet aggregation, the balance of PGI₂/TXA₂ and fibrinolytic system of rats. METHODS Rats were randomly divided into 5 groups: control group, low(1.3 mg??kg^-1), middle(3.9 mg??kg^-1) and high(12.9 mg??kg^-1) dose of dl-PHPB groups and ticlopidine group. Blood was taken from the abdominal aorta 30 min after dl-PHPB administrated intravenously, and the rate of platelet aggregation was detected by platelet aggregometer. The expression of CD62p on the surface of platelet was determined by flow cytometry. The contents of 6-Keto-PGF_1??, thromboxane B₂ (TXB₂), t-PA and PAI-1 in serum were measured by radio-immuno assay and ELISA kit, respectively. RESULTS dl-PHPB inhibited rat platelet aggregation induced by ADP in dose-dependent manner more potently compared with AA, collagen and thrombin. dl-PHPB also decreased the expression of CD62p. It increased the level of 6-keto-PGF_1??, the metabolite of prostaglandin I₂ (PGI₂) and reduced the content of PAI-1. But dl-PHPB had no effect on the contents of TXB_2, the metabolite of TXA₂ and t-PA.CONCLUSION dl-PHPB may significantly inhibit rat platelet aggregation induced by ADP, increase the ratio of PGI₂/TXA₂ and enhance the activity of fibrinolytic system.     

葡萄籽原花青素对血小板聚集与实验性血栓形成的影响

目的 观察葡萄籽原花青素对血小板聚集和实验性血栓形成的影响.方法 ①大鼠血栓形成实验按随机数字表法分为5组:生理盐水(对照)组、阿司匹林(ASP)组(60 mg/kg)及原花青素100 mg/kg、200 mg/kg、400 mg/kg组,每组各10只.②小鼠血栓形成实验按随机数字表法分为5组,生理盐水(对照)组、阿司匹林组(84mg/kg)及原花青素140mg/kg、280mg/kg、560mg/kg组,各10只.实验动物采用二磷酸腺苷(ADP)、胶原(COL)、花生四烯酸(AA)灌胃,诱导大鼠血小板聚集;采用大鼠动-静脉旁路丝线上血检形成和胶原蛋白-肾上腺素诱发小鼠体内血栓形成,两种方法均以阿司匹林为阳性对照.结果 ①原花肯素高、中、低剂量组均可抑制大鼠颈总动脉-颈外静脉血流旁路血栓的湿重:高、中剂量对血栓干重有明显作用,但不及阿司匹林.②原花青素高剂量组可对抗胶原蛋白-肾上腺素混合诱导剂引起的血栓形成,减少动物死亡数.⑨原花青素中、高剂量组均可抑制ADP、COL、AA诱导的大鼠血小板聚集及两种方法引起的实验性血栓形成.结论 原花青素具有抑制实验性血栓形成和抗血小板聚集作用.     

Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers

In this study, we evaluated the synergistic effect of ginger and nifedipine on anti-platelet aggregation in normal human volunteers and hypertensive patients. The results showed that the percentage of platelet aggregation induced by collagen, ADP and epinephrine in hypertensive patients was larger than that in normal volunteers. Either aspirin or ginger could potentiate the anti-platelet aggregation effect of nifedipine in normal volunteer and hypertensive patients. These results suggested that ginger and nifedipine possessed synergistic effect on anti-platelet aggregation. A combination of 1 g ginger with 10 mg nifedipine per day could be valuable for cardiovascular and cerebrovascular complication due to platelet aggregation.     

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??OBJECTIVE To determine the effects of saxagliptin and exenatide on humerus cancellous bone of diabetes-induced osteopenia rats by histomorphometry. METHODS Thirty-five Cases of female SD rats were randomly divided into normal group (N group, n=7), control group (C group, n=7), and the remaining rats were used to establish the type 2 diabetic model by combination of high-fat&sugar-diet feeding for 4 weeks and then low-dose streptozotocin injection(STZ, 30 mg??kg^-1) . After 10 d, the oral glucose tolerance test and the fasting blood glucose were measured, rats with high OGTT(2 h) above 11.1 mmol??L^-1 and high FBG above 16.7 mmol??L^-1 were divided into model group (M group, n=5), saxagliptin group (G group, n=5) and exenatide group (D group, n=6), and continuously treated for 30 d. The left humerus (proximal humeru metaphometry, PHM) were fixed with 4% paraformaldehyde for 48 h, uncalcified embedded in methyl methacrylate after dehydrated and cleared, and sections were taken for bone histomorphometry after Masson-Goldner Trichrome stained. RESULTS In PHM, there was no statistical significance between N and C group, the trabecular bone area ratio( BV/TV) and trabecular quantity were significantly decreased (P??0.01) in M group, while the trabecular separation degree was increased, comparing with those in C group (P??0.01), and the trabecular bone area ratio( BV/TV) and trabecular quantity in G and D group were higher (P??0.01) than those of model rats, while the trabecular separation degree was decreased, comparing with those in M group (P??0.01). Cell parameters showed no statistical significance between N and C group, the osteocllast number and percentage of osteocllast surface perimeter were significantly reduced(P??0.05, P??0.01) in M group, while the osteoclast number and percent osteocllast surface perimeter were significantly increased (P??0.01) as compared with those in C group, saxagliptin and exenatide were found to significantly induce osteocllast number (P??0.01) and percentage of osteoblast surface perimeter (G group P??0.05, D group P??0.01), while reduce osteoclast number (P??0.01) and percent osteoblast surface perimeter (P??0.05) compared with M group. In growth-plate, there was no statistical significance between N and C group, the thickness of growth-plate and the diameter of the mast cells were reduced in M groups (P??0.01), while the thickness of growth-plate (P??0.01) and the diameter of the mast cells (P??0.05) were increased in G and D group,compared with M group. CONCLUSION Therapeutic effects of saxagliptin and exenatide on diabetes -induced osteopenia rats was showed, and the mechanism may be related to the improved growth rate of growth-plate and the changed bone turnover status.     

脑心通对阿司匹林抗血小板治疗的干预作用

目的 探讨小剂量阿司匹林对心脑血管疾病患者血小板生化指标的影响及脑心通的干预作用。 方法 145例心脑血管疾病(糖尿病、高血压病、冠心病和脑梗死)患者服用阿司匹林1周后,检测用花生四烯酸(AA)和二磷酸腺苷(ADP)作诱导剂的血小板聚集率(PAG)、血浆P 选择素和血栓素B2(TXB2)浓度；然后随机分为阿司匹林组和脑心通组，均继续口服阿司匹林，脑心通组加用脑心通胶囊；治疗1个月后复查PAG、血浆P 选择素及TXB2浓度。 结果 第1次检测：血浆P-选择素、TXB2浓度与AA诱导的PAG均呈正相关(r=0.449, r=0.576，P<0.01)，与ADP诱导的PAG均呈正相关(r=0.525, r=0.501,P<0.01)；血浆P-选择素浓度与TXB2浓度呈正相关(r=0.610, P<0.01)；两组间比较3项指标差异无统计学意义(P>0.05)。第2次检测：两组AA和ADP诱导的PAG、血浆P-选择素和TXB2浓度均显著低于第1次检测值(P<0.01)；脑心通组上述指标均显著低于阿司匹林组(P<0.05)；两组不良反应发生率差异无统计学意义(P>0.05)。 结论 心脑血管疾病患者服用阿司匹林1周时抗血小板疗效尚不理想，加用脑心通能提高其抗血小板疗效，且不增加不良反应。     

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??OBJECTIVE To investigate the effect of acute exposure to 4 300 m altitude environments on the body pathophysiological, serum, TNF-?? and IL-1?? of Wistar rats and protective effect of methazolamide on Wistar rats. METHODS Twenty-eight Healthy adult Wistar rats were randomly divided into plain(altitude of 55 m) control group, high altitude(altitude of 4 300 m) model group, high altitude methazolamide group, and high altitude acetazolamide group. After being intragastric administration with 0.9% sodium chloride injection, methazolamide(2 times a day, 2.23 mg??kg^-1) and acetazolamide(2 times a day, 22.33 mg??kg^-1) for 5 consecutive days. The biochemical, blood gas, the pathological results of rats were analyzed. The TNF-?? and IL-1?? content were detected from the blood samples. RESULTS Blood and biochemical results showed the high altitude might cause dehydration in rats. Compared with the plain control group, each index of the high altitude model group changed significantly(P??0.01), compared with the high altitude group, the aspartate transaminase(AST), alanine aminotransferase(ALT), pH value, bicarbonate concentration(cHCO₃^-), buffer base(BB), base excess(BE) of methazolamide and acetazolamide group were significantly decreased(P??0.01), indicated that methazolamide and acetazolamide had protective effect on rat liver. The total protein(TP), urea solution(UREA), partial pressure of carbon dioxide(PaCO₂), sodium concentration(cNa⁺), chloride concentration(cCl^-) were significantly increased(P??0.01), indicated that the high altitude group had metabolic acidosis and respiratory alkalosis, and liver and lung tissue had pathological damaged. Compared with the acetazolamide group, the methazolamide group damaged less. Compared with plain control group, serum TNF-?? of high altitude groups significantly increased, IL-1?? of high altitude groups decreased significantly, which, serum TNF-??, IL-1?? levels of acetazolamide and methazolamide group were significantly higher than high altitude model group(P<0.01). CONCLUSION Methazolamide can improve acute high altitude physiological and biochemical status of rats, reduce inflammatory injury, with a good protective effect of hypoxia.     

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??OBJECTIVE To study the effects of Kadsura coccinea alcohol extract(KCAE) on rats with immunologic hepatic fibrosis and research the possible mechanisms in it. METHODS Totally 60 SD male rats were randomly divided into 6 groups: a normal control group,a model group, a compound Biejia-ruangan tablets group(0.7 g??kg^-1), KCAE high, middle and low dose groups(1.68, 0.84, 0.42 g??kg^-1) at ten in each groups. Except for the normal control group,other groups were duplicated intraperitoneal injection of porcine serum twice a week at dose of 0.5 mL??time^-1. The rats in treatment groups were intragastric administration respectively, meanwhile, the rats in normal control and model groups were treated with the same volume of distilled water, once a day for 15 weeks. The liver was weighed to calculate the liver index. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), total protein(TP), albumin(ALB) and total bilirubin(TB) were evaluated by the Mind-Ray automatic biochaemical analyzer. The expression level of procollagen ??(PC??), collagen type ??(??-C), laminin(LN), hyaluronic acid(HA), transforming growth factor-??1(TGF-??1), interkeukin-10(IL-10), interferon-??(IFN-??) and tumor necrosis factor-??(TNF-??) in serum were detected by ELISA. The degrees of fibrosis were evaluated by HE and Masson straining, and the expression levels of TGF-??₁ in liver tissue were assessed by Western blot. RESULTS Compared with model group, the liver index of KCAE high-dose group was decreased significantly(P??0.01). The expression levels of ALT, AST, TP, ALB, TB were within normal range, the differences were not statistically significant(P>0.05). KCAE could decrease the level of PC??, IV-C, LN, HA, TGF-??₁, TNF-?? and increase the level of IFN-?? in serum. KCAE could alleviate the hepatic fibrosis in rats(P??0.01) and inhibit the expression of TGF-??₁ in the liver tissues significantly(P??0.01). CONCLUSION KCAE has an anti-immunologic hepatic fibrosis effect in rats and the mechanisms possibly involve effectively regulating inflammatory cytokines, reducing extracellular matrix expression and inhibiting the expression of TGF-??₁.     

当归总苯酞活血化瘀作用的实验研究

目的 观察当归总苯酞在活血化瘀方面的功效.方法 大鼠ig给予当归总苯酞(生药1、2、4g/kg),观察当归总苯酞对大鼠实验性动脉血栓形成及血小板聚集功能的影响;采用高分子右旋糖酐制备高黏血症大鼠模型,观察当归总苯酞对大鼠血液黏度的影响;观察当归总苯酞对大鼠凝血相关指标的影响.结果 当归总苯酞(生药1、2、4 g/kg)能延长大鼠实验性动脉血栓的形成时间(P＜0.05、0.01);降低高分子右旋糖苷所致的高黏血症大鼠全血、血浆、血清黏度(P＜0.05);抑制花生四烯酸(AA)、腺苷二磷酸钠(ADP)、胶原(CG)诱导的血小板聚集功能(P＜0.05、0.01、0.001);明显延长大鼠凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT) (P＜0.05、0.01、0.001).结论 当归总苯酞具有显著的活血化瘀作用,表现为延长实验性动脉血栓的形成时间;改善高黏血症模型大鼠的全血及血浆黏度;抑制血小板聚集功能:影响凝血系统,延长大鼠TT、PT、APTT等指标.