玉米须水提物对自发性高血压大鼠血小板聚集功能的影响

目的研究玉米须水提物(AECS)对自发性高血压大鼠血小板聚集功能的影响和机制。方法自发性高血压大鼠随机分为模型组、AECS 5和15 g·kg~(-1)组,WKY大鼠作为正常对照组,各组灌胃给药,连续25 d。第25天取大鼠肝素抗凝血制备富血小板血浆,比浊法检测ADP和胶原诱导的血小板最大聚集率变化,并测定血浆总抗氧化能力、谷胱甘肽和血管紧张素Ⅱ水平。结果与WKY组比较,模型组大鼠ADP(3和10μmol·L~(-1))和胶原(4μg·mL~(-1))诱导的血小板最大聚集率增高,血浆总抗氧化能力和谷胱甘肽水平降低,血管紧张素Ⅱ水平增高;与模型组比较,AECS 5和15 g·kg~(-1)组大鼠在上述浓度ADP和胶原诱导的血小板最大聚集率降低,血浆总抗氧化能力和谷胱甘肽水平增高,血管紧张素Ⅱ水平下降。结论玉米须水提物可抑制自发性高血压大鼠的血小板聚集功能,机制与降低血管紧张素Ⅱ水平和抗氧化应激有关。     

知母有效成分体内外给药对血小板聚集的抑制作用

目的研究知母有效成分(化合物9714)对血小板聚集性的影响。方法采用比浊法测定血小板聚集功能。结果化合物9714代谢产物10-3、10-4、10-5、10-6mol·L-1体外呈浓度依赖性抑制二磷酸腺苷(ADP)、胶原诱导的家兔血小板聚集(P<0.05,P<0.01);化合物971410、20、40mg·kg-1体内(ig)明显抑制ADP、胶原诱导的大鼠血小板聚集,5～7d给药效果较好(P<0.05,P<0.01)。结论化合物9714代谢产物对血小板聚集具有明显的抑制作用。     

异亚丙基莽草酸抗血栓作用的实验研究

目的研究异亚丙基莽草酸(ISA)对大鼠动静脉环路血栓、大脑中动脉栓塞及血小板聚集的对抗作用及机制。方法用动静脉环路血栓及三氯化铁致大脑中动脉栓塞(MCAT)模型观察药物作用;并研究了ISA体内、外给药对血小板聚集的影响。结果ISA 25,50,100及200 mg·kg^-1 ig均可显著降低大鼠体外血栓重量;ISA 50,100,200 mg·kg^-1 ig可明显改善MCAT模型大鼠神经症状;ISA 100及200 mg·kg^-1 ig MCAT模型大鼠脑梗塞范围分别下降27.8%和31.6%;另外,ISA体内、外给药对ADP和胶原诱导的血小板聚集有明显的抑制作用。结论ISA可能通过抗血小板聚集作用抑制血栓的形成。     

人参,西洋参及三七总皂甙对大鼠血小板功能及血栓形成的抑制作用

体外试验表明人参总甙(SPG),西洋参总甙(SPQ)和三七总甙(SPNG)均能抑制胶原诱导的大鼠血小板聚集,其IC_(50)分别为0.583,1.012及0.815mg·ml~(-1),对胶原诱导引起的血小板5-HT释放,在0.5mg·ml~(-1)时,SPG,SPQ及SPNG的抑制率分别为20％,4％及16％,对血小板内cAMP含量,在35mg·kg~(-1)iv后,SPG,SPQ及SPNG均能使其显著增加.体内试验,对大鼠的实验性血栓,SPNG在80mg·kg~1 ig 1.5～2 h后有显著的抑制作用,但同样剂量的SPG无效Rg_1 20mg·kg~1 ig能显著抑制血栓形成,iv能显著抑制凝血酶所致DIC的血小板数目减少,FDP的增加,但对纤维蛋白原,凝血酶原时间的改变则无明显的拮抗作用。     

普罗托品对家兔血小板功能的影响

普罗托品(protopine,Pro)体外(1—1000μmol·L~(-1))和体内(10和20mg·kg~(-1))均抑制ADP,胶原,花生四烯酸(AA)和烙铁头蛇毒血小板聚集素(TMVA)诱导的兔血小板聚集及血小板5-HT释放。Pro不抑制AA诱导的免血小板TXA_2生成。也不升高血小板内cAMP水平,但升高cGMP水平。提示其抗血小板作用的机制与升高血小板内cGMP水平,抑制血小板释放活性物质有关。     

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。     

四氢小檗碱对血小板聚集和血栓形成的抑制作用(英文)

SD大鼠每天ip THB 30 mg·kg~(-1)共3 d或5 d后,使ADP诱导的血小板聚集程度降低;同剂量ip 1 d,3 d或5 d后,使AA诱导的血小板聚集程度降低,THB在体外抑制AA,ADP和胶原诱导的兔血小板聚集,IC_(50)分别为0.86,1.31和1.10 mmol·L~(-1) THB能抑制AA诱导的兔血小板生成血栓素B_2 THB 15—30 mg·kg~(-1)iv明显抑制大鼠静脉血栓的形成。     

三乙酰莽草酸对血小板聚集的抑制作用

目的：研究三乙酰莽草酸（TSA）对血小板聚集功能的抑制作用及其作用机理。方法：用比浊法测定血小板聚集功能,分光光度法测定MDA的含量,放免法测定TXB₂,6-酮-PGF_1α,cAMP和cGMP的含量。结果：TSA 12.5,25,50,100和200 mg.kg^-1 ig明显抑制ADP和胶原诱导的大鼠血小板聚集;TSA 12.5,50和200　mg.kg^-1 ig显著增加大鼠血小板内cAMP水平,但不影响cGMP水平。TSA 200 mg.kg^-1对AA诱导的血小板中MDA的生成,ADP诱导的血小板中TXB2和腹主动脉壁6-酮-PGF_1α的生成有轻度抑制作用。结论：TSA抑制血小板聚集作用部分与血小板内cAMP水平升高有关。     

2-萘-3-(3,4-二甲氧基)苯丙烯酸抗血小板聚集作用及其机理

研究发现,NMPA在体外可抑制花生四烯酸、胶原及凝血酶诱导的家兔血小板聚集,IC_(50)分别为189±9,105±11.0,49.8±16.6μM。小鼠ig NMPA(25mg/kg)后,以ADP诱导的血小板聚集明显受到抑制。大鼠ig NMPA后(52mg/kg一次或10mg/(kg·d)连续7d,出血时间延长、胶原诱导的血小板聚集率下降、丙二醛生成减少、但对动脉壁PGI_2样物质影响较小。说明MNPA的作用机理可能在于改变体内TXA_2/PGI_2比值,而达到抑制血小板聚集的效应。     

苦参碱体内外抗大鼠肝纤维化的作用(英文)

目的:研究体外苦参碱对HSC-T6大鼠储脂细胞和NIH3T3成纤维细胞增殖和胶原合成的影响,以及体内对四氯化碳诱导的大鼠肝纤维化的影响。方法:细胞增殖和胶原合成分别采用结晶紫染色法和[~3H]脯氨酸掺入法。肝纤维化评价以血清透明质酸和肝中羟脯氨酸含量为指标。结果:苦参碱(1～2mmol·L~(-1))显著减少血清刺激的HSC-T6细胞以及NIH3T3细胞增殖和胶原合成;苦参碱(0.25～2mmol·L~(-1))浓度依赖地抑制血小板源生长因子(PDGF)促HSC-T6细胞增殖以及抑制转化生长因子β_1(TGF-β_1)促胶原合成的作用。体内苦参碱(50,100mg·kg~(-1))均能显著降低血清透明质酸和肝脏羟脯氨酸水平。结论:苦参碱阻断PDG和TGF-β_1的作用,抑制储脂细胞增殖和胶原合成可能是其抗肝纤维化作用的机制之一。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.