丙泊酚对老年患者外周血淋巴细胞β1肾上腺素能受体脱敏的影响

目的观察丙泊酚单次静脉给药对老年患者外周血淋巴细胞β1肾上腺素能受体脱敏的影响,探讨丙泊酚循环抑制机制。方法选择拟全麻下行择期手术治疗的老年患者30例,随机分为3组（n=10）。低剂量组（L组）：丙泊酚1．0mg／kg,高剂量组（H组）：丙泊酚2．0mg／kg,对照组（c组）：生理盐水。全麻诱导前,静脉单次注药。给药前后3min,记录SBP、DBP和HR变化,同时抽取外周静脉抗凝血各15mL,Boyum法分离淋巴细胞,免疫印迹法分别检测总蛋白、胞膜和胞浆蛋白中的β1肾上腺素能受体表达,放免法检测异丙肾上腺素刺激的淋巴细胞内cAMP含量。结果与c组比较,L组和H组给药后均可引起SBP、DBP、淋巴细胞内cAMP含量及胞膜B1肾上腺素能受体蛋白水平降低（P〈0．05或P〈0．01）,胞浆B1肾上腺素能受体蛋白水平增加（P〈0．05或P〈0．01）;与L组比较,H组的指标变化明显（P〈0．05）。组间两两比较,淋巴细胞总蛋白中β1肾上腺素能受体水平变化均无显著差别（P〉0．05）。结论丙泊酚单次静脉给药可引起老年患者外周血淋巴细胞B1肾上腺素能受体脱敏,且呈剂量依赖性,与促进β1肾上腺素能受体由胞膜内化进入胞浆有关;β1肾上腺素能受体脱敏可能是丙泊酚的循环抑制机制之一。     

Axonal regeneration of cat retinal ganglion cells is promoted by nipradilol, an anti-glaucoma drug

Neurons in the CNS can regenerate their axons in an environment of the peripheral nervous system, but this ability is limited. Here we show that an anti-glaucoma drug, nipradilol, at low concentration led to a four-fold increase in the number of cat retinal ganglion cells regenerating their axons into a transplanted peripheral nerve 4 and 6 weeks after axotomy. Nipradilol also increased the number of three main regenerating retinal ganglion cell types (alpha, beta, not alpha/beta), and enhanced the rate of axonal regeneration of these retinal ganglion cells. Nipradilol is a donor of nitric oxide and an antagonist of alpha-1, beta-1 and -2 adrenoreceptors, and we therefore examined whether one of these pharmacological effects might be more important in promoting axon regeneration. A nitric oxide donor increased the number of regenerating retinal ganglion cells, but not the rate of axonal regeneration. Denitro-nipradilol (nitric oxide-deprived nipradilol) or a nitric oxide scavenger injected before nipradilol increased the number of regenerating retinal ganglion cells but did not promote regeneration rate. Blockade of individual alpha- and beta-adrenoreceptors did not increase the number of regenerating retinal ganglion cells or the rate of regeneration. From these results, it is suggested that nitric oxide plays a crucial role in mediating the effects of nipradilol on axon regeneration and neuroprotection, and the metabolite of nipradilol supports the effects.     

β_3-肾上腺素能受体基因突变与肥胖儿童膳食干预效果

为分析 β3 肾上腺素能受体 (β3 adr)基因突变与单纯性肥胖儿童对膳食干预应答差异的关系 ,将 47名单纯性肥胖儿童随机分为膳食干预组 (36名 )和对照组 (11名 ) ,膳食干预期 3个月 ,干预前后分别进行膳食调查和体格测量。所有研究对象均采用PCR RFLP方法检测 β3 肾上腺素能受体 (β3 adr)基因中编码多肽链第 6 4位的色氨酸密码子被精氨酸密码子 (Trp6 4Arg)取代的突变。结果显示 ,这 47名肥胖儿童膳食结构中脂肪供能过高 ,占 40 7% ;膳食干预后 ,在膳食干预组中无 β3 adr基因Trp6 4Arg突变者的体重、体质指数(BMI)增长幅度低于非膳食干预组 (P <0 0 5 ) ,而有突变者的体重、BMI增长幅度与非膳食干预组相比 ,则不存在统计学差异。结论认为 β3 adr基因Trp6 4Arg突变可能是单纯性肥胖儿童膳食干预效果较差的原因之一。     

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。     

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.     

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。