镉对雌激素与雌激素受体结合能力影响的实验研究

镉 (Cd)是一种重要的环境和工业毒物 ,也是一种半减期很长的多器官、多系统毒物。镉对雌性哺乳动物的生殖系统具有明显的毒作用[1 3 ] 。研究发现 ,镉能诱导去除卵巢的大鼠子宫增生 ,推测镉诱导子宫增生是由于镉在大鼠体内模拟和发挥了雌激素样作用 ;镉也能刺激雌激素受体 (ER)     

Effect of ovarian steroids on the metabolism of noradrenaline in rabbit uterus

The metabolism of (-)-3H-noradrenaline was examined in uterine slices from ovariectomized rabbits which were either untreated or treated with 17 beta-oestradiol, alone or in combination with progesterone. 17 beta-oestradiol caused uterine enlargement which was not accompanied by a change in the formation per g of O-methylated metabolites (3H-NMN, 3H-VMA, 3H-MOPEG). Accumulation of unchanged 3H-noradrenaline and the formation of deaminated catechols (3H-DOMA and 3H-DOPEG) were decreased per g tissue, but increased per uterine horn. Progesterone produced further enlargement of the oestrogen-dominated uteri which was accompanied by (a) a decrease in deaminated catechol formation and (b) an increase in 3H-NMN formation per unit mass of tissue. In all uteri (control and hormone-treated), cocaine inhibited the formation of deaminated catechols, but not that of the O-methylated metabolites. It is suggested, therefore, that, per unit of uterine mass, the neuronal deamination of (-)-3H-noradrenaline is decreased by 17 beta-oestradiol and further decreased by progesterone, and that these changes reflect failure of the intraneuronal deaminating system in the whole uterus to increase in proportion to the increase in uterine mass. Since other agents which decreased the deamination of (-)-3H-noradrenaline (cocaine and nialamide) did not affect 3H-NMN formation in oestrogen-dominated uteri, it is suggested that stimulation of 3H-NMN formation represents a direct effect of progesterone on the extraneuronal O-methylation of noradrenaline.     

Calcium in relation to the actions of ouabain and adrenaline on the heart

Isolated pairs of rabbit auricles have been observed in media containing 6, 24 or 75 mM-potassium, with corresponding reductions in sodium concentration. In 24 mM-potassium, adrenaline restored beating and excitability, as did calcium chloride, but ouabain had no effect. In 75 mM-potassium, adrenaline had no effect; calcium chloride caused a contracture; ouabain had no direct effect, but auricles which had been beating in the presence of ouabain contracted promptly on transfer to 75 mM-potassium. Left auricles, which do not beat spontaneously, were less sensitive to calcium and to ouabain. The results showed a membrane stabilizing action of calcium and an action on muscular contraction, and suggested that cardiac glycosides acted by causing accumulation of calcium at the activator site in the tissue.     

Cactecholamines and the oedematous reaction to oestradiol in the rat uterus

The effect of catecholamines on the 4 h oedematous reaction to estradiol in the immature rat uterus was investigated. Isoprenaline was found to augment the reaction to suboptimal doses of estradiol (0.25--0.5 microgram/kg. This effect was reversed by d,l-propranolol. Adrenaline and noradrenaline were found to inhibit the reaction to oestradiol 2 microgram/kg. The effect of adrenaline was reversed by phenotalmine.     

女金制剂对子宫活动的影响

目的：研究女金丸和女金囊对离体大鼠子宫及家兔在体子宫活动的影响，方法：雌性大鼠离体子宫，分别采用在浴槽内加入不同剂量的女金丸及女金胶囊，雌性家兔在体子宫，采用十二指肠给药，分别给不同剂量的女金丸及女金胶囊，观察大鼠离体子宫及家兔在体子宫收缩的频率，幅度，活动力的变化。结果：女金丸和女金胶囊对离体大鼠子宫及家兔在体子宫具有舒张作用，并能对抗缩宫素的子宫收缩频率，幅度活动力，结论：女金丸，女金胶囊均能对抗缩宫素对大鼠及家兔子宫收缩作用。     

In vitro characterization of alpha-adrenergic receptor in rabbit detrusor muscle

In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2 alpha, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine greater than PGF2 alpha greater than histamine greater than methoxamine. Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN-A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2-pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10(-5) M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-)- and S(+)-YM-12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively antagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by alpha 1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by alpha 1-adrenergic receptor agonist is smaller than those stimulated by the other receptor agonists.     

The effect of adrenaline, noradrenaline and isoprenaline on the guinea-pig uterus

The actions of adrenaline, noradrenaline and isoprenaline were compared on the isolated guinea-pig uterus. In uteri from immature animals (200 to 350 g) adrenaline caused relaxation which changed to a biphasic effect and finally to a contraction in the course of an experiment (6 to 8 hr). Noradrenaline always caused contraction and isoprenaline relaxation. In uteri from oestrogen-treated animals adrenaline and noradrenaline caused contraction and isoprenaline caused relaxation. Isoprenaline potentiated the contraction produced by adrenaline and reversed the adrenaline relaxation to a contraction. The change of the pharmacological action of adrenaline was not related to the Na⁺ and K⁺ content of the uterus, which remained constant throughout an experiment involving repeated application of the amines. Nor could it be related to a change in the glycogenolytic effect of adrenaline estimated by determinations of total glycogen of the muscle which, however, may not reflect a momentary change in rate of breakdown.     

Dual effect of adrenaline on noradrenaline release in the pithed rabbit

We examined the effects of adrenaline on the noradrenaline release rate and plasma catecholamine levels in the pithed rabbit with electrically stimulated sympathetic outflow (3 Hz). Adrenaline (0.06 micrograms/kg/min) increased the rate of noradrenaline release into the plasma. This increase was prevented by propranolol (0.2 mg/kg + 0.1 mg/kg/h) and probably involves activation of presynaptic beta-adrenoceptors. A higher dose of adrenaline (1.0 micrograms/kg/min) significantly reduced the noradrenaline release rate. The reduction was "reversed" to a facilitatory effect by phenoxybenzamine (4 mg/kg). Propranolol alone slightly inhibited the noradrenaline release rate. After pretreatment with desipramine (1.0 mg/kg + 0.2 mg/kg/h), the inhibitory effect of propranolol on noradrenaline release was more pronounced and blood pressure was also lowered. However, in rabbits pretreated with captopril (1 mg/kg) in addition to desipramine, the sympathoinhibitory effect of propranolol was not observed. These results suggest that adrenaline can activate either presynaptic beta-adrenoceptors to increase noradrenaline release or, in higher doses, presynaptic alpha-adrenoceptors to inhibit noradrenaline release in vivo. The decrease in the noradrenaline release rate produced by propranolol alone may not be due to blockade of facilitatory presynaptic beta-adrenoceptors, but rather to depression of renin secretion. This would decrease angiotensin II formation and hence decrease the presynaptic release-enhancing effect of angiotensin II.     

Effect of progesterone on the metabolism of noradrenaline in rabbit uterine endometrium and myometrium

The metabolism of (-)-3H-noradrenaline was examined in the endometrium and the myometrium from rabbits which had received 17 beta-oestradiol, either alone (oestrogen-dominated) or with progesterone (progesterone-dominated). The progesterone treatment resulted in a 2.5-fold increase in 3H-NMN formation in the endometrium, with no change in 3H-DOPEG, 3H-DOMA or 3H-OMDA formation. In the myometrium, progesterone caused a 5-fold increase in 3H-NMN formation and a 2.5-fold increase in 3H-OMDA formation, but did not affect 3H-DOPEG or 3H-DOMA formation. In the progesterone-dominated endometrium, both 3H-NMN and 3H-OMDA formation were strongly inhibited by cocaine 30 mumol/l. When O-methylation was inhibited by a COMT inhibitor, cocaine prevented the resultant increases in deamination of noradrenaline to 3H-DOPEG and in the accumulation of 3H-noradrenaline by the tissue. The 3H-noradrenaline which accumulated in endometria, in which both MAO and COMT were inhibited, was firmly bound; desipramine 3 mumol/l and (+)-amphetamine 10 mumol/l were equieffective with cocaine 30 mumol/l in inhibiting the accumulation. Cocaine 30 mumol/l was without effect on 3H-NMN and 3H-OMDA formation in the progesterone-dominated myometrium, nor did it prevent the increase in 3H-DOPEG formation produced by COMT inhibition. Fluorescent histochemical analysis of the endometrium indicated that the epithelial cells of the endometrial glands were the site of cocaine-sensitive noradrenaline accumulation. It is concluded that progesterone stimulates O-methylation in the endometrium and myometrium in different ways.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats.

The present study was designed to investigate the possible modulator effect of melatonin on uterine estrogen and progesterone receptors in rats as well as the uterine response to oxytocin. Non-pregnant rats were pretreated with melatonin in a dose of 0.8 mg kg(-1) per day for 15 consecutive days. Control animals received the vehicle. The uterus was dissected out and uterine contraction in one horne was recorded in vitro for each animal as a response to oxytocin (0.5 x 10(-11) to 2 x 10(-11)M). The other uterine horne was subjected to estrogen and progesterone receptors detection by immunohistochemical and image analysis techniques. The results reveal a significant reduction (59%) in the number of uterine estrogen receptors with concomitant increase in the progesterone receptors (53%) in melatonin-pretreated rats as compared to the control ones. In addition, our data show an inhibitory effect of melatonin on the uterine contraction as a response to oxytocin (0.5 x 10(-11), 1 x 10(-11), and 2 x 10(-11)M) amounting to 48, 77, and 59.5% reduction, respectively, in the amplitude of contraction as well as 62, 19.9, and 47% reduction in the area under the curve (AUC) of uterine contractions, respectively. The data, so far obtained, may indicate a possible relationship of melatonin-induced modulation of the number of estrogen and progesterone receptors and its inhibitory effect on uterine contraction. These findings merit further investigations on the possible beneficial role of melatonin in a plethora of hormone-dependent uterine disorders.     

Effect of sex on the cardiovascular response to adrenaline in humans

Cardiovascular responsiveness to stress conditions differs between men and women. It is not known to what extent this observation is explained by differences in the release of stress hormones like adrenaline, or by differences in the response to adrenaline. Therefore, we quantified the hemodynamic response to infusion of adrenaline (0.04, 0.06, and 0.08 microg x kg(-1) x min(-1) for 20 minutes each) in 8 healthy men and 8 healthy premenopausal women. Arterial plasma adrenaline levels were measured before and after infusion. Heart rate and intra-arterial blood pressure were monitored throughout the experiment. Arterial plasma adrenaline levels increased similarly in both sexes. There was a larger increase in systolic blood pressure in women compared with men (17.6 +/- 2.8 versus 5.1 +/- 3.1 mm Hg, P < 0.01). In contrast, men showed a larger increase in heart rate compared with women (20.3 +/- 1.4 versus 11.2 +/- 2.8 bpm, P < 0.01). In conclusion, these data suggest that the cardiovascular response to adrenaline is predominantly alpha-adrenergic in premenopausal women, and predominantly beta-adrenergic in age-matched men.     

Effect of diltiazem on in vitro rabbit bladder function

The relationship between extracellular calcium and urinary bladder function was investigated by studying the effect of the specific calcium antagonist diltiazem on the functional ability of the in vitro whole rabbit urinary bladder to empty in response to pharmacological stimulation. The bladder was found to require an extracellular calcium concentration of 4.5 X 10(-4) M to elicit near complete cholinergic-mediated emptying. Diltiazem (1 X 10(-6) - 1 X 10(-4) M) inhibition of bladder function was competitively antagonized by increasing the extracellular calcium concentration (0.45 X 10(-4) - 3.6 X 10(-4) M). In the absence of diltiazem, alterations in the extracellular calcium concentration between 0.45 X 10(-4) and 3.6 X 10(-4) M had no significant effects on bladder response to bethanechol. KCl-mediated bladder emptying was significantly more sensitive to diltiazem inhibition than was bethanechol-stimulated emptying. Even at the intermediate diltiazem concentration of 1 X 10(-5) M, increasing the extracellular calcium concentration did not completely reverse the inhibitory effect of diltiazem on bladder response to KC1. These findings are consistent with the hypothesis that diltiazem at low concentrations may inhibit extracellular calcium influx while at higher concentrations translocation of intracellular stores of calcium may be inhibited as well. The study also suggests that diltiazem is capable of inhibiting urinary bladder function and deserves further consideration as a possible therapeutic agent in certain forms of urinary bladder dysfunction.     

米索前列醇应用于疤痕子宫剖宫产术中促进子宫收缩的效果观察

目的 观察米索前列醇应用与疤痕子宫剖宫产术中对子宫收缩的促进作用.方法 选取2010年5月至2011年10月期间在我院需行刮宫产的有疤痕子宫的84例产妇,随机分为观察组及对照组各42例,对照组在胎儿娩出后静脉滴注缩宫素20U,子宫体肌注20U,观察组在对照组用药基础上加用米索前列醇400(磺),直肠用药,观察两组术中及术后出血量、用药不良反应.结果 观察组术中及术后出血量分别为(228.73±30.94)ml、(110.32±45.71)ml,对照组分别为(294.88±50.42)ml、(160.29±60.84)ml,观察组术中及术后2h出血量均明显少于对照组,比较差异有显著性(P＜0.05);观察组药物不良反应发生率9.52％,对照组0,比较差异无显著性(P＞0.05).结论 米索前列醇直肠放药,对于疤痕子宫剖宫产的产妇促进子宫收缩作用较单一使用缩宫素效果好,并且用药安全、简单,值得临床推广.     

马来酸麦角新碱注射液对疤痕子宫孕产妇术后子宫复旧的影响

目的 探讨马来酸麦角新碱注射液在疤痕子宫孕产妇术后子宫复旧的有效性。方法 以60例具有剖宫产指征的疤痕子宫患者为研究对象。将患者随机分成观察组和对照组,产后分别给予马来酸麦角新碱和缩宫素治疗3 d。观察两组术后子宫大小变化、出血量、宫腔积液情况及恶露消失时间。结果 术后3、42 d观察组子宫大小三径之和分别为（29.9±2.0）cm、（15.8±±1.2）cm,显著低于对照组的（32.6±2.8）cm、（18.1±1.5）cm（P<0.05）;观察组术后24、48 h出血量、42 d宫腔积液发生率、产后恶露消失时间均显著少于对照组（P<0.05）。结论 马来酸麦角新碱可有效修复剖宫产后子宫,减少术后出血量、产后宫腔积液发生率及缩短恶露消失时间,提高子宫复旧效率。