足月妊娠PGE2及其受体表达与引产成功率的关系

目的研究足月妊娠子宫平滑肌与蜕膜组织中前列腺素E2（Prostaglandin E2,PGE2）的浓度、子宫平滑肌中PGE2受体-2（PGE2 recepor-2,PGER2）蛋白的表达与缩宫素引产成功率的关系。方法选择缩宫素引产成功与缩宫素引产失败的孕妇,于剖宫产术中取子宫平滑肌及子宫蜕膜组织。分别行ELISA法检测组织匀浆中PTGE2的浓度,Western blot检测子宫平滑肌中PTGER2蛋白的表达。结果缩宫素引产成功组比缩宫素引产失败组子宫平滑肌、子宫蜕膜组织中PTGE2浓度显著增高（P〈0．01）;缩宫索引产成功组比缩宫素引产失败组子宫平滑肌组织中PTGER2蛋白的表达也明显增高（P〈0．01）。结论子宫平滑肌与蜕膜组织中PTGE2浓度、子宫平滑肌组织中PTGER2蛋白的表达量与缩宫素引产成功率关系密切。     

离体子宫平滑肌测定方法的改进

目的:探索离体子宫平滑肌测定方法中,使用增氧泵通气取代混合氧为离体子宫平滑肌供氧的可行性。方法:采用RM-6240BD多道生理信号采集处理系统,观察营养液内通入混合氧、增氧泵通气及无通气对离体子宫平滑肌活动力的影响。结果:与营养液内通入混合氧相比,离体子宫平滑肌的活动力在混合氧组与增氧泵通气组间无统计学差异(P0.05),不通气组的频率和活动力均有统计学差异(P0.05或P0.01)。结论:可以使用增氧泵通气为离体子宫平滑肌供氧,既满足了供氧,同时也可促进营养液流动,使离体子宫与营养液充分接触。     

血立停胶囊对早孕大鼠RU486药流后子宫收缩的实验研究

目的:研究血立停胶囊对早孕大鼠Ru486药物流产后对子宫平滑肌收缩频率、收缩幅度及活动力变化的影响,旨在探讨血立停胶囊治疗药物流产后出血的作用机制。方法:选择妊娠Wistar大鼠,随机分为6组,即对照组,米非司酮组,大剂量血立停组,小剂量血立停组,催产素组,止血敏组。于妊娠第7天,开始相应处理,妊娠第14天分别监测以下指标后处死:在体子宫平滑肌收缩力,收缩幅度、收缩频率。结果:大剂量血立停可明显增强大鼠在体子宫平滑肌活动力、提高子宫平滑肌收缩频率、收缩幅度,与对照组比较差异有显著性(p<0.05)。结论:血立停胶囊可增强大鼠子宫平滑肌兴奋性,从而起到对药物流产后阴道出血的治疗作用。     

BCTC和辣椒辣素对卵清蛋白致敏大鼠气管平滑肌张力的影响

目的：评价BCTC和辣椒辣素对气道高反应性大鼠气管平滑肌张力的影响。方法：健康成年SD大鼠32只,每只大鼠第1天和第8天腹腔加皮下注射卵清蛋白致敏,第15天连续雾化吸入卵清蛋白（OVA）三天,激发建立哮喘模型。分离气管平滑肌,随机分为四组,0组（Ovalbumin）卵清蛋白组,OC组（Ovalbumin＋capsaicin）卵清蛋白＋辣椒辣素组,0B组（Ovalbumin＋BCTC）,DSMO组（DSMO＋Ovalbumin）溶剂组。分别在4组溶液的刺激下测定离体气管平滑肌张力的变化。结果：离体气管平滑肌的张力OC组较0组为高;O组气管平滑肌张力比0B组高。结论：辣椒辣素增加致敏离体气管平滑肌张力,BCTC能够降低致敏大鼠气管平滑肌张力,对致敏离体平滑肌有松弛作用。     

元胡止痛胶囊的含药血清对痛经模型动物的影响

目的采用血清药理学实验方法 ,观察元胡止痛胶囊的含药血清对痛经模型动物的影响。方法缩宫素诱发大鼠痛经模型和前列腺素E诱发小鼠痛经模型法,对大鼠离体子宫收缩活动的影响。结果元胡止痛胶囊的含药血清能减少缩宫素所致大鼠扭体反应次数和前列腺素E1所致小鼠扭体反应次数,并能拮抗缩宫素对大鼠离体子宫的收缩作用。结论元胡止痛胶囊的含药血清对痛经模型动物有镇痛作用,并对大鼠离体子宫收缩有解痉作用。     

黄芩苷对家兔离体子宫平滑肌的作用

目的:观察黄芩苷对家兔离体子宫平滑肌收缩的作用及其与Ca2+的关系.方法:制作常规离体家兔子宫平滑肌肌条,考察黄芩苷对子宫肌条反应的影响.结果:(1)黄芩苷(5-10mmol-L-1)剂量依赖抑制子宫平滑肌收缩;(2)黄芩苷对催产素及高K去极化液中Ca2+所致的离体子宫平滑肌收缩均呈剂量依赖性抑制;使CaC12累积量-效曲线非平行性右移,最大效应下降,呈非竞争性抑制;(3)且对子宫平滑肌依细胞内、外Ca2+两种收缩成分均呈抑制作用.结论:黄芩苷对家兔离体子宫平滑肌条的抑制作用,可能与其拮抗Ca2+有关.     

氧氟沙星对小鼠生殖毒性和致畸性的研究

目的研究氧氟沙星对昆明系小鼠胚胎和胎鼠发育的影响,确定其是否存在生殖毒性和致畸性。方法①雄鼠分别灌服各剂量氧氟沙星,连续10d,末次给药24h后与母鼠合笼,在妊娠第三天取胚胎,记录各剂量组胚胎发育率。②孕鼠妊娠零天给药,分别经口灌服高、中、低剂量[36、72和360mg(kg.bw)]氧氟沙星溶液,连续给药3d,在妊娠第三天收集胚胎,记录胚胎发育率。③孕鼠妊娠零天给药,分别经口灌服各剂量氧氟沙星溶液,连续给药10d,在妊娠第16天取出胎鼠,记录胎鼠体重、胎盘重、活胎数、胎鼠外观畸形和内脏畸形等指标。结果给药组与对照组相比,雄鼠服用高剂量组360mg(kg.bw)氧氟沙星对着床前胚胎发育影响显著(P<0.05),而中等剂量和低剂量组对着床前胚胎发育的影响不显著(P>0.05)。雌鼠服用不同剂量氧氟沙星对着床前胚胎发育影响不显著(P>0.05)。氧氟沙星对受孕鼠的活胎数和吸收胎数均无明显影响,给药组的活鼠体重、胎盘重均未见明显差异(P>0.05);药物组和对照组均未出现外观畸形和内脏畸形,也不存在剂量和效应关系。结论孕鼠服用不同剂氧氟沙星对昆明系小鼠胚胎和胎鼠发育无明显的影响,表明氧氟沙星对雌性鼠不具有明显的生殖毒性和致畸性;但雄鼠服用高剂量氧氟沙星对着床前胚胎发育影响显著。     

姜黄素对小鼠离体十二指肠平滑肌舒缩活动的影响

目的:本研究采用小鼠离体十二指肠平滑肌观察姜黄素对胃肠道蠕动的影响,探讨其作用机制。方法:取小鼠离体十二指肠平滑肌条,放入37℃Krebs液浴槽中,通入95%氧气和5%二氧化碳混合气体,分组进行下列实验:对照组和分别加入10-40 M姜黄素组,测量记录十二指肠平滑肌的自主收缩变化;另取一组平滑肌条,分对照组、乙酰胆碱组、乙酰胆碱+姜黄素组、阿托品组、阿托品+姜黄素组,采用张力换能器连接多通道生理信号采集处理系统,测量比较十二指肠平滑肌舒缩的变化。结果:小鼠十二指肠平滑肌加入姜黄素孵育后,其自主收缩幅度有明显下降(P0.01),而且降低的幅度与姜黄素剂量相关;给与乙酰胆碱引起十二指肠收缩后,再加姜黄素孵育,十二指肠平滑肌的收缩幅度明显的下降(P0.01);给予阿托品引起小鼠平滑肌舒张后,再给予姜黄素孵育,平滑肌收缩幅度进一步降低。结论:姜黄素对小鼠离体十二指肠平滑肌具有直接舒张作用。     

不同声强超声对孕鼠子宫收缩及胎鼠神经损伤的影响及机制

目的:探讨不同声强超声对孕鼠子宫收缩及胎鼠神经损伤的影响及机制。方法:将32只孕鼠随机分为A(0)组、B(2)组、C(4)组、D(8)组,每组各8只,分别接受声强为0 W cm~(-2)、2 W cm~(-2)、4 W cm~(-2)和8 W cm~(-2)的超声辐照20 min。记录孕鼠子宫收缩及子宫平滑肌ATP酶的活力,检测胎鼠大脑皮层与海马神经元凋亡及胆碱能神经系统相关酶的活力。结果:超声增加孕鼠子宫收缩频率、收缩幅度、收缩张力和子宫活动度(P均0.05),降低孕鼠子宫平滑肌中钠钾ATP酶、钙ATP酶和钙镁ATP酶的活性(P均0.05)。超声降低胎鼠大脑皮层和海马中Bcl~(-2)水平(P0.05),增加Bax和Caspase-3水平(P均0.05)。以及促进乙酰胆碱酯酶活力,降低乙酰胆碱和乙酰胆碱转移酶水平(P均0.05)。且4 W cm~(-2)和8 W cm~(-2)的超声比2 W cm~(-2)超声对这些指标的作用更强。结论:4 W cm~(-2)和8 W cm~(-2)超声可能通过降低ATP酶的活性促进孕鼠子宫平滑肌收缩,并可引起胎鼠大脑皮层和海马神经元损伤,机制可能与胆碱能神经元系统失衡有关,2 W cm~(-2)声强的超声对胎鼠神经元损伤甚小。     

大黄素对大鼠离体空肠平滑肌收缩的影响

目的：观察大黄素（emodin）对大鼠离体空肠平滑肌收缩功能的影响,并探讨其作用机制。方法：大鼠离体空肠标本随机分为7组（n=6）：对照组,大黄素剂量组（1,5,10,20μmol／L）,普萘洛尔（PRO）加大黄素组,格列苯脲（GLI）加大黄素组,NG-基-L厂精氨酸甲酯（1．NAME）加大黄素组,无钙K-H液对照组及无钙K-H液大黄素组。采用颈椎离断法处死大鼠并分离其空肠,将肠段标本与张力换能器相连并置于氧饱和的K-H液中。采用BL-420E＋生物信号采集处理系统记录大鼠空肠平滑肌的收缩张力（TE）,幅度（AM）和频率（FR）的影响。结果：①大黄素能使大鼠离体空肠平滑肌的收缩张力和幅度明显下降,且呈剂量依赖性（P〈0．05,P〈0．01）;对频率无明显影响。②普萘洛尔（P〈0．05）、格列苯脲（P〈0．01）可部分阻断大黄素对空肠平滑肌的抑制作用。③L．NAME对大黄素所引起的空肠平滑肌的抑制作用无影响。④氯化钙所引起的空肠平滑肌收缩可被大黄素所抑制（P〈0．01）。结论：大黄素能明显减弱大鼠离体空肠平滑肌的收缩张力和收缩幅度,对收缩频率无影响。这种作用可能是通过兴奋肾上腺素8受体、兴奋ATP敏感钾通道、阻断细胞膜上钙离子通道实现。     

Morinda lucida reduces contractility of isolated uterine smooth muscle of pregnant and non-pregnant mice.

The present work investigated the effect of Morinda lucida (M. lucida) extract on isolated uterine smooth muscle of pregnant and non-pregnant mice. Pregnant and non-pregnant mice were pretreated with oral stilboesterol (0.1 mg/kg body weight) and killed by cervical dislocation. Thin strips of the uterus were cut and mounted in a 20ml organ bath containing De Jalon solution bubbled with 95%O2-5% CO2 gas mixture. The strips were connected to a force transducer coupled to a Grass 7D Polygraph for the recording of isometric tension. Effects of graded concentrations of oxytocin (OXY; 10-5-10-2 mol/L), acetylcholine (ACh; 10-9-10-5 mol/L) and M. lucida extract (0.015-1.5 mg/ml) were recorded. Fresh uterine strips were then incubated with M. lucida extract for 5mins and cumulative response to OXY was repeated. Another set of fresh strips was incubated in L-NAME for 15mins and the cumulative responses to M.lucida extract were repeated. OXY resulted in increased contractile responses in both pregnant and non-pregnant uterine muscles. M. lucida resulted in relaxation of the uterine smooth muscle in both pregnant and non-pregnant mice at all doses. However, at 1.5mg/ml, M. lucida completely blocked spontaneous uterine contractions. Following incubation with L-NAME, M. lucida extract led to a slightly greater relaxation of the uterine strips. In conclusion, M. lucida reduced contractility of uterine smooth muscle in both pregnant and non-pregnant mice as well as blocking contractile responses to OXY and Ach in uterine smooth muscle of pregnant and non-pregnant mice. There was no significant alteration of M. lucida activity by L-NAME suggesting that the action of the compound on uterine muscle is not associated with impaired nitric oxide synthase.     

Neutral metalloendopeptidase associated with the smooth muscle cells of pregnant rat uterus

The pregnant rat uterus contains a membrane-bound metalloendopeptidase that is biochemically and immunologically similar to kidney enkephalinase (E.C.3.4.24.11). The uterus enzyme readily cleaved specific neutral endopeptidase substrates and oxytocin as well as the synthetic elastase substrate, Suc(Ala)3-pNA, yet did not digest native elastin. Using specific inhibitors, the uterus endopeptidase was identified as a metallopeptidase and not a serine protease, having an absolute requirement for zinc and perhaps calcium for maximal activity. The uterus endopeptidase cross-reacted with polyclonal antiserum to kidney microvillar endopeptidase and a monoclonal antibody to common acute lymphocytic leukemia antigen. Immunohistochemical localization of the enzyme in a 17 day pregnant uterus indicated that the enzyme was localized on the smooth muscle bundles of the myometrium and the endometrial epithelium. Total enzyme activity was 25 times higher in the late-term pregnant uterus (17th day of pregnancy) than in the nonpregnant uterus. Enzyme levels dropped rapidly prior to parturition and within 4 days after delivery the enzyme activity had returned to control levels. Inhibition of NEP in uterine strips with phosphoramidon resulted in a marked potentiation of oxytocin-induced contractions. Our results suggest that the uterine endopeptidase may have an important role in regulating uterine smooth muscle cell contraction during the later stages of pregnancy through its action on oxytocin and perhaps other biologically active peptides.     

Changes in kinetic properties of oxytocin receptors in longitudinal muscle membranes of rat uterus during gestation

Receptors of oxytocin were found to occur in the membrane fraction obtained from longitudinal muscle of pregnant rat uterus. The affinity of the membrane receptor for oxytocin increased through an increase in the association rate and a decrease in the dissociation rate during gestation. The membrane oxytocin receptor concentrations rose almost three-fold from Day 15 to Day 21. A transition of oxytocin receptors from a single class of independent sites to site–site interacted multiple binding sites, which most likely exhibit positive cooperativity during the last seven days of gestation, was observed. These results suggest that changes in the dynamics of uterine oxytocin receptors also play an important role in the onset of labor.     

Sensitivity of the Bothrops jararaca snake uterus to oxytocin and acetylcholine

The influence of hormones on the uterine smooth muscle sensitivity has been demonstrated in mammals; however in nonmammalian species much remains to be clarified. This study investigated the sensitivity of the snake (Bothrops jararaca) uterus to oxytocin and acetylcholine. The snakes were divided into three experimental groups: snakes with uterine segments weighing ≤20.00 mg (A), snakes with uterine segments weighing between 20.01 and 35.00 mg (B) and snakes with uterine segments weighing ≥35.01 mg (C). The histomorphometric analysis of the uterus showed an increase in the smooth muscle layer thickness in groups B and C, when compared with group A, suggesting different hormonal conditions of the animals. Cumulative concentration-effect curves to oxytocin and acetylcholine were obtained in uteri of the three experimental groups and the pD₂ values determined. The sensitivity of the snake uterus to oxytocin increased in groups B and C (concentration-effect curves shifted to the left and pD₂ values increased) when compared with group A. The concentration-effect curves to acetylcholine were biphasic and shifted to the left, suggesting two binding sites (low and high affinity binding sites) in snake uteri of groups B and C. These results suggest that sex steroids may modulate the sensitivity of the snake uterus to oxytocin and acetylcholine.     

Inhibitory effect of GnRH on isolated rat uterine muscle contractility

The effect of GnRH upon uterine contractions of both non-pregnant and pregnant rats was examined in vitro. In the non-pregnant rat uterus, GnRH inhibited in a concentration-and-time dependent manner the contractions induced by acetylcholine and oxytocin, but not those caused by bradykinin and angiotensin II. GnRH also inhibited the rhythmic contractions induced by oxytocin in uterine strips from late pregnant rats. These findings show that GnRH has a direct inhibitory effect on the rat uterine contractions, suggesting that GnRH-like substances may exert modulatory influences upon rat uterine contractility.     

Physiological studies on nonpregnant and pregnant uterus in experimentally diabetic rats]

Spontaneous intraluminal pressure waves of diabetic nonpregnant uterus and contractile responses to oxytocin and prostaglandin F2 alpha (PGF 2 alpha) of both diabetic nonpregnant and diabetic pregnant uterus were investigated in vitro. Diabetes was induced by streptozotocin (STZ), 60 mg/kg for nonpregnant and 50 mg/kg for pregnant rats. Frequency of spontaneous intraluminal pressure waves of nonpregnant uterus was reduced in diabetic rats when compared with normal, but amplitude was slightly larger in diabetic than in normal uterus. Pressure-volume curves revealed that the compliance of nonpregnant diabetic uterus was remarkably reduced. Normal tubal side-circular muscle was significantly more sensitive to oxytocin and PGF 2 alpha than cervical one in contractile responses. This tendency was lost in diabetic nonpregnant uterus. Contractile responses of both tubal and cervical circular muscles to oxytocin were lower in nonpregnant diabetic than in normal rats, but those of longitudinal muscles were higher in diabetic nonpregnant than in normal rats. Cervical circular muscle of pregnant diabetic rats was more sensitive to both agents than those of normal. However, contractile responses of diabetic longitudinal muscle to both agents were higher than those of normal as in the case of nonpregnant uterus. The mechanism of diabetic changes of the nonpregnant and pregnant uterus was discussed.     

Adaptation of uterine artery thick- and thin-filament regulatory pathways to pregnancy

Little is known about the adaptation of uterine artery smooth muscle contractile mechanisms to pregnancy. The present study tested the hypothesis that pregnancy differentially regulates thick- and thin-filament regulatory pathways in uterine arteries. Isometric tension, intracellular free Ca(2+) concentration, and phosphorylation of 20-kDa myosin light chain (MLC(20)) were measured simultaneously in uterine arteries isolated from nonpregnant and near-term (140 days gestation) pregnant sheep. Phenylephrine-mediated intracellular free Ca(2+) concentration, MLC(20) phosphorylation, and contraction tension were significantly increased in uterine arteries of pregnant compared with nonpregnant animals. In contrast, phenylephrine-mediated Ca(2+) sensitivity of MLC(20) phosphorylation was decreased in the uterine arteries of pregnant sheep. Simultaneous measurement of phenylephrine-stimulated tension and MLC(20) phosphorylation in the same tissue indicated a decrease in MLC(20) phosphorylation-independent contractions in the uterine arteries of pregnant sheep. In addition, activation of PKC produced significantly lower sustained contractions in uterine arteries of pregnant compared with nonpregnant animals in the absence of changes in MLC(20) phosphorylation levels in either vessels. In uterine arteries of nonpregnant sheep, the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase inhibitor PD-098059 significantly increased phenylephrine-mediated, MLC(20) phosphorylation-independent contractions. The results suggest that in uterine arteries, pregnancy upregulates alpha(1)-adrenoceptor-mediated Ca(2+) mobilization and MLC(20) phosphorylation. In contrast, pregnancy downregulates the Ca(2+) sensitivity of myofilaments, which is mediated by both thick- and thin-filament pathways.