Kentanserin对大鼠心肌缺血 再灌注损伤的影响

为探讨５ ＨＴ２受体与心肌缺血 再灌注损伤的关系,观察５ ＨＴ２受体阻断剂ｋｅｎｔａｎｓｅｒｉｎ对心肌缺血 再灌注大鼠室颤及左室内压＋ｄｐ／ｄｔｍａｘ及－ｄｐ／ｄｔｍａｘ的影响。结果表明,ｋｅｎｔａｎｓｅｒｉｎ可拮抗缺血性心功能障碍和再灌室颤。提示５ ＨＴ２受体参与了缺血性心功能障碍和再灌室性心律失常的发生。     

5-HT6受体及其拮抗剂研究进展

5-羟色胺能神经系统与认知功能和摄食行为密切相关。目前研究人员正在对多种化合物进行生物评价,以确定其是否具有5-HT₆受体拮抗作用。临床前研究结果表明,部分化合物对大鼠和人5-HT₆受体具有较强的选择性拮抗作用,并能增强大鼠的认知功能,包括记忆保存与巩固,以及空间学习能力。因此,5-HT₆受体拮抗剂在治疗神经精神疾病相关的认知损伤方面（如阿尔茨海默病、精神分裂症）较有前景。另外,这些化合物还有助于减少遗传型和饮食型肥胖者的食物摄入、脂肪吸收和体重增加。本文介绍了5-HT₆受体拮抗剂用于治疗阿尔茨海默病和精神分裂症相关的认知功能障碍,以及肥胖症的研究进展。     

缺血/再灌注及预处理对糖尿病大鼠心肌梗死范围的影响

冠状动脉粥样硬化是糖尿病患者常见并发症。然而有关糖尿病心肌缺血/再灌注损伤变化特点的报道不多且相互矛盾。有人指出糖尿病大鼠心肌缺血后心功能恢复较正常鼠慢^[1];有人报道糖尿病动物对缺血耐受性更高^[2～4];还有人认为糖尿病及正常动物对心肌缺血/再灌注损伤的反应无明显差别^[5].鉴于心肌结构改变影响心功能及心电,本工作通过观察心肌缺血/再灌注及缺血预处理(ischemia preconditioning,IP)对糖尿病大鼠心肌梗死范围的影响,了解糖尿病大鼠缺血/再灌注后心肌损害程度及心肌自身保护作用有否变化。     

血栓素B2的高效液相荧光测定及刺五加提取物的抗血小板作用

本文在Turk及Wintersteiger荧光衍生实验的基础上,建立了反相HPLC法测定血小板TXB₂含量的方法.血小板TXB₂用Sep-PakC₁₈提取,在冠醚和碳酸钾存在下,BrMmc与TXB₂的羧基反应生成BrMmc-TXB₂。然后经Zorbax-ODS柱(250mm×4.6mm,5μm)分离,测定荧光强度(E×345,Em405)。流动相为乙腈:水:磷酸(60:40:0.1V/V),流速1ml/min.BrMmc-TXB₂的分离在20min内完成。TXB₂的含量用外标法定量,检测限15ng。体外实验刺五加提取物(0.275～2.2mg/mlPRP)对AA、ADP诱导的家兔血小板聚集有明显的抑制作用,并能抑制AA诱导的血小板TXB₂的生成。静脉注射(120mg/kg)对AA、ADP诱导的聚集也有抑制作用。     

去甲肾上腺素对豚鼠缺血及再灌注性室颤的作用

目的 :探讨去甲肾上腺素 (NE)在缺血性室颤及缺血 /再灌注性室颤发生中的作用及机制。方法 :运用高效液相色谱 电化学法测定离体豚鼠缺血性室颤心脏 (n =2 4 )及缺血 /再灌注性室颤心脏 (n =2 6 )流出液中NE的含量 ,并与未发生室颤心脏 (n =2 9)相比较 ,用全细胞膜片钳记录技术检测NE对缺氧豚鼠心肌细胞 (n =8)钙通道电流 (ICa)的影响。结果 :发生缺血性室颤心脏及缺血 /再灌注性室颤心脏NE释放量明显高于未发生室颤心脏 (P <0 0 1) ;NE可明显增加缺血及缺血 /再灌注心肌细胞ICa(P <0 0 1,P <0 0 5 )。结论 :NE增加心肌细胞ICa为其致缺血及缺血 /再灌注性室颤的机制之一。     

前列腺素E1脂微球载体制剂对体外循环中患者血液系统的影响

目的探讨前列腺素E1脂微球载体制剂(Lipo-PGE₁)对体外循环(CPB)中患者血液系统的影响。方法将20例施行心脏瓣膜置换术患者随机分为观察组和对照组各10例,观察组于CPB开始至结束匀速3ng／(kg·min)泵入Lipo-PGE1,预充液中加入5ng／mL,对照组用等容量生理盐水。测定肝素化后(T₁)、CPB开始30min(T₂)及CPB结束即刻(T₃)、CPB结束1h(T₄)、CPB结束24h(T₅)5个时点血浆血栓素B₂(TXB₂)、6-酮-前列腺素F1α(6-Keto-PGF1α)、游离血红蛋白(F-HB)的浓度值。结果两组中TXB2、6-Keto-PGF1α及其比值、F-HB在CPB过程中均显著升高,CPB结束时达峰值,各时点与T1比较差异有统计学意义(P<0.05)。在相应时间点,观察组6-Keto-PGF1α明显高于对照组,TXB₂、TXB₂／6 Keto-PGF1α、F-HB明显低于对照组(P<0.05)。结论Lipo-PGE₁能纠正CPB中TXB₂与6-Keto-PGF1α比值的失衡,改善患者的凝血功能;降低血浆中F-HB的浓度,减轻由红细胞破坏引起的机体溶血,对患者的血液系统有一定的保护作用。     

心脑通络液对腹主动脉粥样硬化家兔TXB2、hs-CRP的影响

[目的] 通过心脑通络液对腹主动脉粥样硬化兔血浆血栓素B₂（TXB₂）及血清高敏C反应蛋白（hs-CRP）的影响,探讨心脑通络液对动脉粥样硬化的治疗作用。[方法] 选取雄性新西兰兔40只,随机分成5组,即空白组、模型组、血脂康组、心脑通络液高剂量组（简称高剂组）、心脑通络液低剂量组（简称低剂组）,每组8只。造模成功后,连续治疗3个月,观察兔血清TXB₂及hs-CRP的水平变化。[结果] 与空白组对比,模型组TXB₂及hs-CRP值显着升高（P<0.05）.血脂康组及高、低剂量组的TXB₂及hs-CRP值均减低,且高剂组TXB₂及hs-CRP值与血脂康组相比差异无统计学（P>0.05）.[结论] 心脑通络液对动脉粥样硬化家兔有治疗作用。     

缺血性室颤和再灌注室颤发生率的比较研究

为探讨缺血性室颤和再灌注室颤的发生率究竟谁高谁低，作者在麻醉后的在体猪心上共进行了１２７次不同程度、不同时间的缺血及缺血后再灌注实验。结果共发生室颤１３次，室颤发生率为１０．２％，其中缺血性室颤１１次，占８５％，再灌注室颤２次，占１５％。此结果表明，在本实验条件下，室颤主要由缺血引起，再灌注室颤只占１５％。本实验中，２例缺血性室颤在未充分恢复再灌前，直流电除颤失败，而在恢复再灌后，所有室颤皆经直流电除颤恢复窦性心律，提示充分恢复再灌对电击除颤治疗可能是有益的。     

烟酸对大鼠急性坏死性胰腺炎合并肺损伤的防治作用

采用牛磺胆酸钠诱发大鼠急性坏死性胰腺炎并发肺损伤模型,用放射免疫分析法动态测定大鼠血浆TXB₂、6-keto-PGF_1α质量浓度变化,并观察烟酸的防治作用.结果显示,急性坏死性胰腺炎组血浆TXB₂质量浓度升高,TXB₂/6-keto-PGF_1α显着升高,应用烟酸能明显降低TXB₂质量浓度,TXB₂/6-keto-PGF_1α比值显着降低,也降低了肺系数,改善肺组织病理形态变化.提示TXB₂、PGI₂平衡改变可能是急性坏死性胰腺炎并发肺损伤的病理机制之一,烟酸具有防治急性坏死性胰腺炎并发肺损伤的作用.     

定点突变对BPI23-Fcγ1重组抗菌蛋白表达和复性率的影响

为提高BPI₂₃-Fcγ1重组抗菌蛋白在原核表达系统中的表达和复性率,采用定点突变法改造pBV-BPI₆₀₀-Fcγ1₇₀₀重组表达载体,转化E.coliDH5α后,通过温控诱导表达.结果表明:①突变后BPI₂₃-Fcγ1重组抗菌蛋白表达量比突变前提高约10%;②表达时间提前约1h;③抗菌活性未受影响;④复性率未见显着提高.     

Effects of Amrinone on Cardiac Contraction and Relaxation in Isolated，Perfused Rat Heart

(马业新)(赵华月)ＥｆｆｅｃｔｓｏｆＡｍｒｉｎｏｎｅｏｎＣａｒｄｉａｃＣｏｎｔｒａｃｔｉｏｎａｎｄＲｅｌａｘａｔｉｏｎｉｎＩｓｏｌａｔｅｄ，ＰｅｒｆｕｓｅｄＲａｔＨｅａｒｔ￥ＭＡＹｅ－ｘｉｎ；ＺＨＡＯＨｕａ－ｙｕｅ（ＤｅｐａｒｔｍｅｎｔｏｆＩｎｔｅｒｎ...     

Effect of Yiqi Huoxue Recipe (益气活血方) on cardiac function and ultrastructure in regression of pressure overload-induced myocardial hypertrophy in rats

Objective:To investigate the effect of Yiqi Huoxue Recipe (YHR,益气活血方)on the cardiac function and ultrastructure during the regression of myocardial hypertrophy induced by pressure overload in rats.Methods:The model of myocardial hypertrophy was established by abdominal aortic banding.Eighty male Wistar rats were divided into six groups,the normal control groupⅠ(n=20),the normal control groupⅡ(n=12),the hypertension model groupⅠ(n=12),the hypertension model groupⅡ(n=12),the YHR group(n=12)and the Captopril group(n=12).The observation was carried out in the normal control groupⅠand the hypertension model groupⅠafter 4 weeks of modeling,and the other four groups were observed after 16 weeks of modeling(12 weeks of administration).The cardiac function was measured with a multichannel biological signal analysis system,and the myocardium ultrastructure was observed by a transmission electron microscope. Results:(1)Compared with the normal control groupⅠ,the systolic blood pressure and cardiac coefficient(left ventricular weight/body weight)in the modelⅠgroup was higher(P<0.05,P<0.01). (2)In the YHR group,cardiac coefficient and-dp/dt_(max)were lower,left ventricular systolic pressure and dp/dt_(min)were higher when compared with the model groupⅡand the Captopril group(P<0.05 or P<0.01).In the Captopril group,only cardiac coefficient was lower when compared with the mode groupⅡ(P<0.05).(3)Compared with the normal control groupⅡ, dp/dt_(max)was higher(P<0.01), -dp/dt_(max)and isovolumetric contraction time(ICT)was lower(P<0.05,P<0.01)in both the YHR group and the Captopril group.(4)Results of the myocardium ultrastructure showed edema under myocardium plasmalemma,enlarged sarcoplasmic reticulum and T tube,and significantly enlarged intercalated disc of the cardiac muscle in the model groups.In the Captopril group,the extension of sarcoplasmic reticulum and T tube as well as the pathological changes of intercalated disc were lighter,with slight edema under the myocardium plasmalemma.In the YHR group,the expansion of the sarcoplasmic reticulum was less than in the Captopril group,part of the pathological changes of intercalated discs was slightly more severe than that in the Captopril group,the dissolution of nuclear chromatin was not found,which was similar to that of the Captopril group,and no injury of the nucleus was found,either.Conclusion:YHR could reverse myocardial hypertrophy in rats with abdominal aortic banding and improve the systolic and diastolic function of the left ventricle.The ultrastructure of the myocardium such as arcoplasmic reticulum,intercalated disc,and cell nucleus in abdominal aortic banding rats could be partly reversed by the recipe.     

Wirkung des kardialen β-adrenergen Rezeptorsystems im linksventrikulären Remodeling bei herzinsuffizienten Patienten

To study the role of myocardium β-adrenoceptors pathway in ventricular remodeling of heart failure patients, β-adrenegic receptor density (B_max) and the content of cAMP were measured in the papillae of left ventricle and blood lymphocyte of 20 patients suffered from heart failure (CHF) (NYHZ classification II to III) B_max were investigated using³H-dihydroalpheolol as ligand. cAMP were assessed by competitive immunoassay. Left ventricle mass index (LVMI) were measured using echocardiogram. The results showed that the B_max and cAMP in failing myocardium significantly negatively correlated with LVMI (r=?0. 77,P < 0.01 andr=?0.46P < 0.05 respectively); the B_max of myocardium and blood lymphocyte in CHF patients with NYHA I (63 ± 12 fmol/mgpro and 514±115 fmol/10⁷ cell) significantly lowered than that of NYHA I. patients (94±20 fmol/mgpro and 702 ±138 fmol/10⁷ cell); and the B_max of myocardium and blood lymphocyte in patients with abnormal LVMI (62±12 fmol/mgpro and 516±122 fmol/10⁷ cell) decreased more significantly than that with normal LVMI patients; even in nromal LVMI patients (92±21 fmol/mgpro and 682±146 fmol/10⁷ cell), the B_max of blood lymphocyte was already decreased (P < 0.01), when comparing with controls. The intralymphocyte cAMP content sygnificantly decreased than that of controls (P < 0.05). These results indicated that B_max could reflect the severity of ventricle remodeling and the impairment of myocardium. The regulation of myocardium intracellular messenger transduction was earlier than the pathologic structural change of LV remodeling.     

内源性一氧化氮与缺血/再灌性室性心律失常的关系

为探讨内源性一氧化氮(NO)在缺血/再灌性室性心律失常发生中的作用,观察缺血/再灌注损伤早期的室性心律失常(VA),血中NO及心肌一氧化氮合成酶(NOS)活性.结果:①缺血/再灌组(I/R组)动物缺血及再灌注期各种心律失常均高于对照组(P<0.01),而血中NO含量皆低于对照组(P<0.05).VA等级与NO含量呈负相关(r=0.74514,P<0.05).提示:血中NO量的减少与缺血/再灌注性VA增加有密切关系.②I/R组与对照组心肌中NOS活性无显着差异.提示血中NO减少,可能不是生成减少而是消耗增多所致.     

黄芩甙对缺血再灌注大鼠心肌损伤的保护作用

采用大鼠心肌缺血再灌注模型观察黄芩甙对缺血再灌注后心律失常和心肌损伤的保护作用。实验大鼠分为假手术组、缺血再灌注组、黄芩甙I组、黄芩甙II组和维拉帕米组。观察对各组大鼠心电图、血清磷酸肌酸激酶(CPK)、谷胱甘肽过氧化物酶 (GSH PX)及心肌组织内超氧化物歧化酶 (SOD)、脂质过氧化物丙二醛 (MDA)的影响。结果表明 ,黄芩甙可显著减少再灌注性心律失常发生率 ,降低CPK活性和MDA含量 ,升高SOD和GSH PX活性。提示黄芩甙对再灌注心肌具有保护作用 ,其机制可能与其抗脂质过氧化反应有关     

壬基酚对大鼠5-羟色胺及其2A受体的影响

目的 观察壬基酚(NP)对大鼠血浆和尿液中5-羟色胺(5-hydroxy tryptamine,5-HT)及血小板中5-HT和5-HT2A受体含量的影响,探讨壬基酚对大鼠5-HT和5-HT2A受体影响的毒效应机制。方法 将24只SD雄性大鼠分为阴性对照组和NP低、中、高剂量组[30、90、270mg/(kg·d)],隔日灌胃染毒28d后检测大鼠血浆中5-HT、血小板中5-HT和5-HT2A受体含量,并检测灌胃后收集到的24h尿液中5-HT的含量。结果 染毒28d后,随NP暴露的剂量增加,各组大鼠血浆、血小板及尿液中5-HT含量升高,血小板中5-HT2A受体表达则下降。NP暴露中、高剂量组大鼠血浆及血小板中5-HT含量均高于对照组(P<0.01;P<0.01),NP暴露高剂量组大鼠血小板5-HT2A受体表达低于对照组(P<0.01)。第4~28天,NP暴露低、中、高剂量组大鼠的尿液5-HT含量均高于对照组(P<0.01)。结论 NP暴露剂量与大鼠血小板5-HT、5-HT2A受体及血浆和尿液中5-HT含量均呈剂量-效应关系,提示NP通过影响大鼠5-HT水平和5-HT2A受体表达而产生毒效应。     

Inhibition of 5-HT3 receptors-activated currents by cannabinoids in rat trigeminal ganglion neurons

This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The results showed that: (1) The majority of examined neurons (78.70%) were sensitive to 5-HT (3-300 μmol/L). 5-HT induced inward currents in a concentration-dependent manner and the currents were blocked by ICS 205-930 (1 μmol/L), a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01-1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners. The concentra-tion-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value. The EC50 values of two curves were very close (17.5±4.5) mmol/L vs. (15.2±4.5) mmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HT3 by (48.65±4.15)%; (3) Neither AM281, a selective CB1 receptor antagonist, nor AM630, a selective CB2 receptor antagonist re-versed the inhibition of I5-HT3 by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application, inhibitory effect was gradually increased and the maximal inhibition took place at 90 s, and the inhibition remained at the same level after 90 s. We are led to concluded that-WIN55,212-2 inhibited I5-HT3 significantly and neither CB1 receptor antagonist nor CB2 receptor an-tagonist could reverse the inhibition of I5-HT3 by WIN55,212-2. Moreover, WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor. WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner. The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2, but the mechanism by which WIN55,212-2 in-hibits I5-HT3 warrants further investigation.     

缺血/再灌注损伤对大鼠心肌内源性可溶性糖基化终末产物受体分泌的影响

目的观察在体大鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)及离体培养心肌细胞单纯缺氧(hypoxia,H)或缺氧/复氧(hypoxia/reoxygenation,H/R)损伤时,血浆或培养基中可溶性糖基化终末产物受体(soluble receptor for advanced glycationend-products,sRAGE)含量的变化,了解缺血/再灌注对内源性sRAGE的影响。方法采取结扎冠状动脉左前降支的方法复制在体大鼠心肌缺血/再灌注损伤模型,分别测定缺血前10 min(BI-10)、缺血45 min时(I-45)、再灌注60 min时(R-60)、再灌注120min时(R-120)和再灌注180 min时(R-180)的左室功能指标,包括心率(heart rate,HR)、左室收缩末压(left ventricular end systolicpressure,LVESP)、左室内压最大上升/下降速率(the maximum rate change of left ventricular pressure,±LVdp/dtmax);采用TTC染色法测定心肌梗死范围;采用酶联试剂盒测定血浆sRAGE浓度。培养乳鼠心肌细胞,复制缺氧/复氧损伤(H/R)模型,测定培养基sRAGE浓度和应用比色法测定乳酸脱氢酶(lactate dehydrogenase,LDH)活力。结果与假手术(sham)组相比较,I/R组I-45、R-60、R-120、R-180各时间点的HR、LVESP、±LVdp/dtmax均降低;在I/R组内,与BI-10相比,I-45、R-60、R-120、R-180各时点的sRAGE含量均降低。与control组相比,离体心肌细胞H(H/R)组的sRAGE含量差异无统计学意义。结论 I/R损伤血浆sRAGE含量降低,这可能与心肌缺血/再灌注损伤有关;而内源性sRAGE改变可能不是心肌细胞源性的。     

开心解郁汤对抑郁症大鼠模型行为、单胺类神经递质、大脑5 -羟色胺受体亚型表达的调节作用

Objective:To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction(开心解郁汤,KJD)by investigating the effects of KJD on behavior,monoamine neurotransmitter levels,and serotonin(5-HT)receptor subtype expression in the brain in a rat model of depression.Methods:The rat depression model was established using chronic unpredictable mild stress(CUMS).Forty-eight Sprague Dawley rats were randomly divided into control,depression model(CUMS),CUMS±KJD(7.7 g/kg~(-1)·d~(-1)of crude drug),and CUMS+fluoxetine(2.4 mg/kg~(-1)·d~(-1))groups(n=12 in each group),and the treatments lasted for 21 days.We regularly evaluated body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests.The content of the monoamine neurotransmitters 5-HT,norepinephrine(NE),and dopamine(DA)and the DA metabolite homovanillic acid in the cerebral cortex,and 5-HT_(1A)and 5-HT_(2A)receptor mRNA in the cerebral cortex and the hippocampus,were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.Results:Compared with the control group,CUMS rats showed a variety of depression-like behavioral changes,including a significant reduction in body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests(P0.05 or P0.01),and a significant decrease in 5-HT and NE levels and 5-HT_(2A)receptor mRNA expression.In contrast,they showed a significant increase in 5-HT_(1A)receptor mRNA expression in the cerebral cortex.In the hippocampus,5-HT_(1A)receptor mRNA expression was lower whereas 5-HT_(2A)receptor mRNA expression was higher than in the control group(P0.05 or P0.01).Treatment with KJD or fluoxetine partially attenuated these changes(P0.05 or P0.01).Conclusion:KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT_(1A)and 5-HT_(2A)receptor expression in rat cerebrum,and this may be one of mechanisms of antidepressant effects of KJD.