血管紧张素Ⅱ对不同年龄大鼠心脏α_1肾上腺素受体介导正性变力效应的影响

目的研究在不同年龄组大鼠,激动血管紧张素Ⅱ受体(ATR)对α1肾上腺素受体(α1-AR)介导的心肌正性变力效应的影响是否不同。方法测定Wistar大鼠离体左心房收缩效应。结果在3.5月龄大鼠离体左心房,血管紧张素Ⅱ(AngⅡ)0.001~30μmol.L-1未能诱导出正性变力效应。在3.5,12,18和24月龄组大鼠,苯肾上腺素(PE)引起左心房浓度依赖性正性变力效应。与3.5月龄大鼠相比,12月龄大鼠的PE累积浓度-收缩效应曲线无明显变化,18和24月龄大鼠的最大收缩反应(Rmax)及pD2值均明显下降。AngⅡ100nmol.L-1预处理30min对3.5和12月龄大鼠左心房的PE累积浓度-收缩效应曲线没有明显影响,但使18和24月龄大鼠的PE累积浓度-收缩效应曲线左移,Rmax及pD2增大。结论AngⅡ不能诱导大鼠心肌正性变力效应。但随着年龄增长,心肌α1-AR反应性降低时,激动ATR可增强α1-AR介导的正性变力效应。     

卡维地洛对老年心力衰竭患者心功能及神经内分泌的影响

目的探讨老年心力衰竭患者应用卡维地洛治疗后对心功能及神经内分泌的影响。方法老年心力衰竭患者84例,分为卡维地洛治疗组和常规治疗组,每组各42例。两组患者心脏基础疾病、入院时纽约心脏协会(NYHA)分级和常规心力衰竭治疗用药无显著差异。卡维地洛治疗组在常规抗心衰治疗基础上接受卡维地洛递增剂量治疗。比较治疗前、卡维地洛达到维持量时和维持量治疗6个月后两组患者心功能指标、血浆脑钠素(BNP)和肾上腺髓质素(ADM)浓度。结果两组患者在治疗过程中心率、血压及左心室内径均逐渐下降,左心室射血分数逐渐增加,血浆BNP和ADM浓度也显著下降。在达维持量时两组之间上述指标变化程度大致相同,而在维持量治疗6个月后卡维地洛治疗组与常规治疗组比较,心率(70次/min∶84次/min,P<0.01)、舒张压(73.2mmHg∶79.1mmHg,P<0.05)、左室舒张末期内径(53.8mm∶60.1mm,P<0.05)和收缩末期内径(38.5mm∶45.8mm,P<0.01)、BNP浓度(178.6pg/ml∶289.3pg/ml,P<0.01)和ADM浓度(24.92pg/ml∶31.28pg/ml,P<0.05)的平均值显著下降,左心室射血分数显著增加(45.2%∶40.1%,P<0.01)。结论老年心力衰竭患者在常规抗心衰治疗的基础上给予卡维地洛治疗在改善心功能状态的同时,可进一步减慢心率、缩小左心室容积、拮抗神经内分泌,对左心室收缩功能的恢复及改善预后具有重要的意义。     

肥胖男性β3肾上腺素能受体基因多态性研究

目的研究单纯性肥胖男性β3肾上腺素能受体（β3-adrenergic receptor，β3-AR）Trp64Arg多态性的分布情况及对肥胖类型的影响。方法利用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）方法检测单纯性肥胖患者及正常对照β3-AR基因Trp64Arg突变。进一步比较不同类型肥胖中突变的发生率。结果β3-AR基因Trp64Arg突变频率在正常对照组、周围性肥胖组及中心性肥胖患者中分别为16．67％、21．05％、34．78％，Arg等住基因在3组中的频率依次为8．33％、10．53％、19．57％。中心性肥胖患者Trp64Arg突变及Arg等住基因频率较正常对照及周围性肥胖者明显增加，但无统计学差异。结论β3-AR基因Trp64Arg突变可能与男性单纯肥胖者腹内脂肪积聚有关，对此需进一步扩大样本后加以研究。     

Modulation of spontaneous myometrial activity in chronically instrumented ovariectomized sheep

The uterine electromyogram (EMG) and intrauterine pressure curves (IUP) were investigated as indicators of myometrial activity in chronically instrumented, ovariectomized ewes. Spontaneous electrical activity was characterized by rhythmic patterns of trains of bursts accompanied by IUP waves. Administration of adrenergic (propranolol or phentolamine) or cholinergic (atropine) blocking agents had no effect on spontaneous uterine activity. Both oxytocin and PGF2 alpha appeared to stimulate spontaneous myometrial activity. 17beta-Estradiol temporarily depressed uterine activity in a dose-dependent fashion. The period of relaxation was followed by a pronounced increase in activity. Progesterone treatment resulted in long-term suppression of myometrial activity. Oxytocin and PGF2alpha increased EMG and IUP activity during estradiol suppression but not after progesterone treatment. These results indicate that the myometrium is active in chronically instrumented, ovariectomized ewes. The autonomic nervous system or its receptors do not play a role in the maintenance of spontaneous myometrial activity, estradiol and progesterone suppress myometrical activity but by different mechanisms.     

Neuroprotective effects of brimonidine against transient ischemia-induced retinal ganglion cell death: a dose response in vivo study

The purpose of this study was to investigate the dose-response effects of topically administered brimonidine (BMD) on retinal ganglion cell (RGC) survival, short and long periods of time after transient retinal ischemia. In adult Sprague-Dawley rats, RGCs were retrogradely labeled with the fluorescent tracer fluorogold (FG) applied to both superior colliculi. Seven days later, the left ophthalmic vessels were ligated for 90 min. One hr prior to retinal ischemia, two 5 microl drops of saline alone or saline containing 0.0001, 0.001, 0.01 or 0.1% BMD were instilled on the left eye. Rats were processed 7, 14 or 21 days later and densities of surviving RGCs were estimated by counting FG-labeled RGCs in 12 standard regions of each retina. The following have been found. (1) Seven days after 90 min of transient ischemia there is loss of approximately 46% of the RGC population. (2) topical pre-treatment with BMD prevents ischemia-induced RGC death in a dose-dependent manner. Administration of 0.0001% BMD resulted in the loss of approximately 37% of the RGC population and had no significant neuroprotective effects. Administration of higher concentrations of BMD (0.001 or 0.01%) resulted in the survival of 76 or 90%, respectively, of the RGC population, and 0.1% BMD fully prevented RGC death in the first 7 days after ischemia. (3) Between 7 and 21 days after ischemia there was an additional slow cell loss of approximately 25% of the RGC population. Pre-treatment with 0.1% BMD also reduced significantly this slow cell death. These results indicate that the neuroprotective effects of BMD, when administered topically, are dose-dependent and that the 0.1% concentration achieves optimal neuroprotective effects against the early loss of RGCs. Furthermore, this concentration is also effective to diminish the protracted loss of RGCs that occurs with time after transient ischemia.     

Tetrandrine and related bis—benzylisoquinoline alkaloids from medicinal herbs：cardiovascular effects and mechanisms of action

Tetrandrine(TET),a bis-benzylisoquinoline alkaloid purified and identified an active ingredient in a Chinese medicinal herb,Radix Stephanae tetrandrae,has been used traditionally for the treatment of congestive circulatory disorder and inflammatory diseases.TET,together with a few of its structural analogues,has long been demonstrated to have antihypertensive action in clinical as well as animal studies.Presumably,the primary anti-hypertensive action of TET is due to its vasodilatory properties.TET prevents or inhibits vascular contraction induced by membrane depolarization with KCl or α-adrenoceptor activation with phenylephrine (PE).TET(30μmol/L) also inhibits the release of endothelium-derived nitric oxide(NO) as well as NO production by inducible NO synthase.TET apparently inhibits multiple Ca^2 entry pathways as demonstrated in cell types lacking the L-type Ca^2 channels.In cardiac muscle cells,TET inhibits both L-and T-type Ca^2 channels.In addition to its actions on cardiovascular tissues,TET may also exert its anti-hypertensive action via a Ca^2 -dependent manner on other tissues intimately involved in the modulation of blood pressure control,such as adrenal grands.In adrenal glomerulosa cells,KCl-or angiotensin II-induced aldosterone synthesis is highly dependent on extracellular Ca^2 .Steroidogenesis and Ca^2 -influx in bovine adrenal glomerulosa cells have been shown to be potently inhibited by TET.In bovine adrenal chromaffin cells,TET inhibits Ca^2 currents via L-and N-type channels as well as other unidentified channels with IC50 of 10μmol/L.Other than the Ca^2 antagonistic effects.TET also interacts with the α-adrenergic receptors and muscarinic receptors based on functional as well as radioligand binding studies.Apart from its functional effects,TET and related compounds also exert effects on tissue structures,such as remodelling of hypertrophied heart and inhibition of angiogenesis,probably by causing apoptotic responses.TET is also known for its anti-inflammatory and anti-fibrogenic actions,which make TET and related compound potentially useful in the treatment of lung silicosis,liver cirrhosis,and rheumatoid arthritis.     

The effects of yohimbine plus L-arginine glutamate on sexual arousal in postmenopausal women with sexual arousal disorder

This study examined the effects of the nitric oxide-precursor L-arginine combined with the ₂-blocker yohimbine on subjective and physiological sexual arousal in postmenopausal women with Female Sexual Arousal Disorder. Twenty-four women participated in three treatment sessions in which self-report and physiological (vaginal photoplethysmograph) sexual responses to erotic stimuli were measured following treatment with either L-arginine glutamate (6 g) plus yohimbine HCl (6 mg), yohimbine alone (6 mg), or placebo, using a randomized, double-blind, three-way cross-over design. Sexual responses were measured at approximately 30, 60, and 90 min postdrug administration. The combined oral administration of L-arginine glutamate and yohimbine substantially increased vaginal pulse amplitude responses to the erotic film at 60 min postdrug administration compared with placebo. Subjective reports of sexual arousal were significantly increased with exposure to the erotic stimuli but did not differ significantly between treatment groups.     

福莫特罗治疗支气管哮喘的多中心临床研究

目的:比较2种长效肾上腺素β2受体激动药福莫特罗治疗支气管哮喘的疗效和安全性。方法:采用多中心、随机、双盲、双模拟、平行对照试验方法,临床研究共分为2部分。(1)连续2 wk用药观察:试验组59例和对照组64例,分别口服福莫特罗试验药或对照药及模拟药40μg,bid,疗程14 d。观察病人症状、体征、肺功能(FEV1和PEF)的变化。(2)即刻疗效观察:试验组和对照组各24例,分别口服单一剂量的福莫特罗试验药或对照药40μg及模拟药。观察病人服药后FEV1和PEF改善达15％的时间和改善≥15％的疗效持续时间。结果: (1)治疗2 wk后,试验组哮鸣音的改善优于对照组(P< 0．05),咳嗽、痰量、喘息、呼吸困难及FEV1和PEF的2组间比较,无显著差异(P>0．05)。试验组临床有效率为95％,对照组为92％。试验组FEV1及PEF有效率分别为66％,75％,对照组FEV1及PEF有效率分别为55％,72％。2组间比较无显著差异(P>0．05)。(2)服用单一剂量药物后,试验组FEV1和PEF改善达15％的起始时间分别为(2．0±s 2．1)h, (2．6±2．8)h,对照组分别为(2．3±2．7)h,(3±4)h。试验组FEV1和PEF改善≥15％的疗效持续时间分别为(6±4)h, (6±4)h,对照组分别为(6±4)h,(5±4)h。2组间比较均无显著差异(P>0．05)。(3)2组治疗耐受性均较好,不良反应发生率均为30％。结论:2种福莫特罗治疗支气管哮喘均具有较好的临床疗效、肺功能疗效及安全性,且两者疗效和安全性相似。     

受体阻断治疗女性膀胱过度活动症的疗效观察

目的探讨采用受体阻断治疗女性膀胱过度活动症的效果。方法不使用抗菌药物,分别选用M胆碱受体阻滞剂、α-受体阻滞剂、钙离子阻滞剂及盐酸黄酮哌酯,或加用三环类抗抑郁药阿米替林治疗113例女性膀胱过度活动症患者,观察治疗的效果。结果113例患者中治愈78例(69%),好转27例(24%),无效8例(7%)。结论针对女性膀胱过度活动症患者采用受体阻断治疗效果较好。     

新生儿肺血管神经支配的组织化学和免疫组织化学研究

采用免疫组化、诱发荧光和胆碱酯酶组化方法，对新生儿肺血管的神经支配进行了系统观察，自肺门处较大的肺动脉、支气管动脉直至直径３５μｍ的微动脉壁均可见有神经分布。肾上腺素能神经布于动脉的外膜及中膜；胆碱能神经、血管活性肠肽（ＶＩＰ）能神经见于动脉外膜与中膜交界处。３种神经仅见于静脉的外膜层。直径＜１ｍｍ的小静脉未见任何神经分布。在相同部位的血管壁上，肾上腺素能神经的密度高于胆碱能及ＶＩＰ能神经。在较大的肺血管周围可见粗细不等的神经束、神经丛及ＡＣｈＥ阳性小神经节。在肺内支气管树粘膜下层的小血管和腺体周围亦可见小的神经丛及单个的ＡＣｈＥ阳性神经元。但未发现有肾上腺素能和ＶＩＰ能神经节或神经细胞。