中药对豚鼠胆囊肌条运动影响的实验研究

目的：观察乌梅、芫花、巴豆对豚鼠胆囊肌条运动的影响。方法：用8个灌流肌槽同时记录实验动物胆囊肌条的自发收缩活动。结果：①低浓度的乌梅对胆囊肌条的收缩活动具有抑制作用(P&;lt;0．01，t=3．918)，而高浓度的乌梅对胆囊肌条张力的影响则呈现先降低后增高的双向性反应(P&;lt;0．05，t=2．297)。普萘洛尔、吲哚美辛、雷尼替丁、六烃季胺、L-NNA均末阻断乌梅对肌条的作用(P&;gt;0．05)。②芫花和巴豆均可增高离体胆囊肌条的张力(P&;lt;0．01，t=16;t=11．79)、加快收缩频率(P&;lt;0．01，t=5．47；t=4．00)、减小收缩波平均振幅(P&;lt;0．01，t=12．37；t=10．5)。③酚妥拉明、苯海拉明、吲哚美辛可部分阻断芫花和巴豆对胆囊肌条的作用。另外，六烃季胺可部分阻断巴豆的作用。结论：①乌梅对豚鼠胆囊肌条的作用可能是直接作用于平滑肌。②芫花和巴豆对胆囊肌条的作用与肾上腺能α受体、组胺H1受体、前列腺素合成酶有关。而巴豆还与胆碱能N受体有关。     

雌性激素对骺生长板闭合过程的影响

目的:了解雌性激素对骺生长板闭合过程的影响。方法:实验于2003-07/2004-03在重庆医科大学动物实验中心完成。选用性发育前(12周龄)的新西兰雌兔40只,切除双侧卵巢后随机分为雌二醇组和对照组各20只,4周后(16周龄)雌二醇组肌肉注射雌二醇(140 μg/kg,1次/周),对照组肌肉注射等体积不含雌二醇的灭菌棉籽油。从16周龄开始2组中各抽取5只动物,每两周1次进行跟踪股骨X射线拍片,直至29周龄,测定股骨生长率。血清雌二醇测定采用ELISA法。两组分别于20,23,26周龄时各处死5只,取股骨远端、胫骨近端和胫骨远端骺生长板作组织病理学分析及组织计量学测定,了解雌性激素对骺生长板生理性闭合时间、骺生长板组织形态结构和软骨细胞增殖率的影响。结果:雌兔40只全部进入结果分析。①血清雌二醇水平:干预前2组比较差异不显著,肌肉注射雌二醇后各时期雌二醇组均高于对照组(P<0.05)。②股骨生长率:两组均随年龄增长逐渐降低,至性成熟后(28周龄)股骨生长基本趋于停止。雌二醇组性发育早期(18周龄)快于对照组[(2.5±0.20),(2.2±0.05)mm/周,P<0.05],但20周龄后增长逐渐减慢,低于对照组。③骺生长板闭合时间:两组动物在20周时胫骨远端生长板均已发生闭合,雌二醇组胫骨近端和股骨远端生长板在23～26周龄闭合,而对照组闭合的时间延长或实验结束时仍未发生闭合。④骺生长板组织形态结构:雌二醇组雌兔骺生长板厚度和细胞柱密度显著低于对照组(P<0.05),对照组骺生长板出现“病理性”增厚。⑤生长板软骨细胞增殖率:雌二醇组股骨远端和胫骨近端生长板软骨细胞增殖率在20和23周龄均高于对照组(P<0.05),26周龄时,雌二醇组大部分雌兔骺生长板已经闭合,对照组仍可检出。结论:雌性激素早期可促进骺生长板软骨细胞增殖,提高长骨生长率,作用中、后期引起骺生长板组织结构发生衰退性改变促进骺生长板生理性闭合过程。     

避孕药与孕激素对绝经过渡期功能失调性子宫出血止血效果的比较

目的：探讨避孕药及大剂量孕激素治疗绝经过渡期功能性子宫出血（功血）的止血效果和适宜的起始剂量。方法：对我院在2000年1月至2004年12月诊断绝经过渡期功血82例患者的临床资料进行回顾性分析。结果：本组82例中口服避孕药（妈富隆）组44例，口服孕激素[安宫黄体酮（MPA）]组38例。快速控制出血率和快速止血率、控制出血时间和完全止血时间两组比较差异有显著性。起始剂量妈富隆≤3片组与〉3片组控制出血时间和完全止血时间无明显差异；MPA组≤20mg组和〉20mg组亦无明显差异。结论：用口服避孕药治疗绝经过渡期功血在控制出血方面效果比MPA好，增加上述各药的剂量，并不增强其止血效果。     

雌孕激素及其受体对卵巢癌的影响

卵巢癌已成为妇科肿瘤死亡的一个重要因素。研究表明雌孕激素及其受体可能与卵巢癌的发生有关，雌激素在卵巢表面上皮细胞（OSE）向肿瘤的转化中起作用，它可能是通过刺激OSE的有丝分裂和抗凋亡作用实现的；孕激素可能不是抗卵巢癌的保护性因子；而雌孕激素受体在卵巢癌组织存在异常表达。因此，研究雌孕激素及其受体与卵巢癌的关系对辅助诊断和治疗卵巢癌有重要的作用。     

绝经后女性冠心病患者雌性激素测定的临床意义

[目的]探讨绝经后女性雌性激素的变化及其与冠心病的关系.[方法]采用微粒子化学发光免疫分析技术测定48例绝经后女性冠心痛患者和40例正常对照组血清雌二醇(E2)、孕酮(P)、催乳素(PRL)、促卵泡激素(FSH)、促黄体激素(LH),并进行显著性检验.[结果]绝经后女性冠心病患者组较对照组的E2明显降低,差异具有显著性(P<0.01).其余差异均无显著性(P>0.05).[结论]绝经后女性冠心痛患者E2水平明显减低,它与动脉粥样硬化之间存在一定的相关性.     

头孢曲松钠对豚鼠胆囊收缩功能影响的实验研究

目的研究头孢曲松钠对豚鼠胆囊收缩功能的影响,以更好地指导临床用药。方法将60只豚鼠随机分为四组,A组(空腹对照组)、B组(饱餐对照组)、C组(空腹实验组)和D组(饱餐实验组)。对实验组C组、D组肌肉注射头孢曲松钠,建立头孢曲松钠相关性胆囊模型。造模成功后,对四组豚鼠的胆囊体积、胆汁量、胆汁及血清中胆汁酸、丙氨酸氨基转移酶(ALT)及胆囊收缩素(CCK)含量及胆囊组织中胆囊收缩素A受体(CCK-AR)基因的表达等进行测定。结果 C组和饱餐实验组的胆囊体积均显著高于A组和B组,表明头孢曲松钠可显著增高豚鼠的胆囊体积(P0.05);实验组豚鼠的胆汁量均显著高于对照组(P0.05),表明实验组豚鼠胆囊内出现胆汁淤积。胆汁中实验组豚鼠的胆汁酸水平均显著低于对照组;而血清中实验组豚鼠的胆汁酸水平均显著高于对照组(P0.05),表明实验组胆汁中胆汁酸的浓度出现下降,而血清中胆汁酸的含量则呈上升趋势。实验组豚鼠的ALT含量显著高于对照组豚鼠,表明头孢曲松钠可致豚鼠ALT水平升高。血清及胆囊组织中实验组的CCK水平均显著低于对照组;实验组胆囊组织中CCK-AR mRNA的相对表达量均显著低于对照组(P0.05)。结论头孢曲松钠可降低血清及胆囊组织中CCK的含量,并抑制CCK受体基因的表达,从而减弱胆囊的收缩功能,导致胆囊内出现胆汁淤积,促进结石的形成。为减少此类不良反应的发生,临床上应尽量避免长期、大剂量的使用头孢曲松钠。     

雌激素对血管内皮功能的影响

流行病学资料表明,绝经前女性心血管疾病的发生率及病死率低于男性,但绝经后快速上升,甚至超过男性,绝经后妇女应用激素替代疗法能使冠心病的发生率和死亡率降低约50%[1].上述事实提示雌激素具有心血管保护作用.早期的研究发现雌激素替代治疗(HRT)能够改善血脂代谢紊乱,但雌激素对血脂代谢的影响仅能解释它的抗动脉粥样硬化作用的25%～50%[2].于是,人们的注意力开始转移到雌激素对血管壁,尤其是对血管内皮细胞的作用. 　　……     

雌激素对血管内皮功能的影响

流行病学资料表明 ,绝经前女性心血管疾病的发生率及病死率低于男性 ,但绝经后快速上升 ,甚至超过男性 ,绝经后妇女应用激素替代疗法能使冠心病的发生率和死亡率降低约 5 0 %[1] 。上述事实提示雌激素具有心血管保护作用。早期的研究发现雌激素替代治疗 (ＨＲＴ)能够改善血脂代谢紊乱 ,但雌激素对血脂代谢的影响仅能解释它的抗动脉粥样硬化作用的2 5 %～ 5 0 %[2 ] 。于是 ,人们的注意力开始转移到雌激素对血管壁 ,尤其是对血管内皮细胞的作用。内皮组织覆盖在整个血管管腔的表面 ,不仅是循环血液和血管平滑肌之间的天然屏障 ,还具有活跃的…     

中药对豚鼠胆囊肌条运动影响的实验研究

目的观察乌梅、芫花、巴豆对豚鼠胆囊肌条运动的影响. 方法用 8个灌流肌槽同时记录实验动物胆囊肌条的自发收缩活动. 结果①低浓度的乌梅对胆囊肌条的收缩活动具有抑制作用( P< 0.01,t=3.918),而高浓度的乌梅对胆囊肌条张力的影响则呈现先降低后增高的双向性反应 (P< 0.05,t=2.297).普萘洛尔、吲哚美辛、雷尼替丁、六烃季胺、 L-NNA均末阻断乌梅对肌条的作用 (P >0.05).②芫花和巴豆均可增高离体胆囊肌条的张力 (P< 0.01,t=16; t=11.79)、加快收缩频率 (P< 0.01,t=5.47; t=4.00)、减小收缩波平均振幅 (P< 0.01,t=12.37; t=10.5).③酚妥拉明、苯海拉明、吲哚美辛可部分阻断芫花和巴豆对胆囊肌条的作用.另外,六烃季胺可部分阻断巴豆的作用. 结论①乌梅对豚鼠胆囊肌条的作用可能是直接作用于平滑肌.②芫花和巴豆对胆囊肌条的作用与肾上腺能α受体、组胺 H1受体、前列腺素合成酶有关.而巴豆还与胆碱能 N受体有关.     

雌激素对血管内皮功能的影响

流行病学资料表明,绝经前女性心血管疾病的发生率及病死率低于男性,但绝经后快速上升,甚至超过男性,绝经后妇女应用激素替代疗法能使冠心病的发生率和死亡率降低约50%[1].上述事实提示雌激素具有心血管保护作用.早期的研究发现雌激素替代治疗(HRT)能够改善血脂代谢紊乱,但雌激素对血脂代谢的影响仅能解释它的抗动脉粥样硬化作用的25%～50%[2].于是,人们的注意力开始转移到雌激素对血管壁,尤其是对血管内皮细胞的作用.     

Characterisation of left ventricular relaxation in the isolated guinea pig heart

The time constant of left ventricular pressure fall, τ, has frequently been used as a measure of myocardial relaxation in the blood-perfused, ejecting heart. The aim of the present study was to characterise τ in relation to β-adrenergic activation, coronary perfusion pressure and flow as well as cardiac oxygen supply and demand in the isolated, isovolumically beating heart. Therefore, τ was analysed from digitised left ventricular pressure data in a total of 23 guinea pig hearts perfused with saline at constant pressure (60 cmH₂O). The coronary venous adenosine concentration ([ADO]) served as an index of myocardial oxygenation. Isoprenaline (0.4–3.2 nmol l⁻¹) decreased and propranolol (3–9 μmol l⁻¹) increased τ dose-dependently (linear regression τ vs lg ([isoprenaline]),r=0.74; τ vs. lg([propranolol]),r=0.66, bothP<0.05). During graded reductions in cardiac oxygen supply from 96.1±12.6(SEM) to 44.4±4.4 μl min⁻¹ g⁻¹, τ was prolonged from 61.5±12.7 to 109.9±22.6 ms while left ventricular developed pressure (LVDP) decreased from 90.7±7.2 to 40.7±5.1 mmHg. In parallel, [ADO] increased from 23.7±9.1 to 58.0±19.1 pmol ml⁻¹ (P<0.05). Increasing oxygen supply to 165.4±32.4 μl min⁻¹ g⁻¹ augmented LVDP to 102.7±7.3 mmHg but did not change τ or [ADO]. There was a dual response of τ to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, τ remained constant. However, when the oxygen supply was less than 100 μl min⁻¹g⁻¹, left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition, a close relationship was observed between [ADO] as an indicator of myocardial oxygenation and τ (Spearman correlation,r=0.99,P<0.005). We conclude that the time constant of left ventricular pressure fall, τ, sensitively reflects myocardial relaxation in the isolated, isovolumically beating guinea pig heart. Moreover, in this model left ventricular relaxation is not influenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather, relaxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.     

聚焦超声对慢性湿疹模型豚鼠皮肤淋巴细胞和角质形成细胞凋亡的影响

目的探讨聚焦超声诱导慢性湿疹模型豚鼠皮肤淋巴细胞和角质形成细胞凋亡的作用及其机制。方法健康豚鼠40只,每只背部剃毛2处,应用2,4-二硝基氯苯为抗原,小剂量多次刺激豚鼠皮肤制备慢性湿疹模型。将模型随机分为1W组和2W组,自身空白对照。辐照后在24、48h采用TUNEL法和免疫组化法观察2W组、1W组和对照组细胞凋亡及Bcl-2和Bax蛋白表达情况。结果辐照组的皮肤淋巴细胞和角质形成细胞凋亡率和Bax蛋白表达高于对照组,2W组高于1W组,48h高于24h。辐照组Bcl-2蛋白表达低于对照组。Bcl-2蛋白表达与凋亡细胞率呈负相关,Bax与凋亡细胞率呈正相关。结论聚焦超声辐照豚鼠慢性湿疹模型可明显提高Bax的表达,抑制Bcl-2的表达,进而促进慢性湿疹动物模型皮肤淋巴细胞和角质形成细胞的凋亡。     

豚鼠结肠肌间神经丛促皮质激素释放激素神经元的表达及其生理特性

目的：研究促皮质激素释放激素(corticotrophin releasing hormone，CRF)在豚鼠结肠肌间神经丛的表达和生理功能。方法：RT-PCR、免疫荧光组织化学染色检测CRF在结肠肠肌层神经丛的表达；细胞内电生理记录结合生物素示踪法研究CRF在肠道的生理功能。结果：豚鼠的肠肌间神经丛有CRF mRNA的表达；豚鼠结肠肠肌间神经丛中有表达CRF的神经元，其形态均为DogielⅠ型神经元。CRF对豚鼠结肠肌间神经丛有很强的兴奋作用，可诱发慢的兴奋性去极化反应，而且CRF所兴奋的神经元均为表达CRFI受体的神经元。结论：CRF是肠道神经系统的兴奋性神经递质。     

Comparison of the therapeutic efficacy of oral doses of fluconazole and itraconazole in a guinea pig model of dermatophytosis

The therapeutic efficacy of orally administered fluconazole (FLCZ) and itraconazole (ITCZ) in a guinea pig model of dermatophytosis was compared, using the infection intensity of local skin tissue as an index. After Trichophyton mentagrophytes infections had been established in the test animals, the antifungal agents were administered once per day for 14 days. FLCZ had a dose-dependent therapeutic effect and significantly ameliorated infections at doses of 10 and 20 mg/kg per day (both P < 0.01) compared with the untreated control group. The pathogen could not be cultured from previously infected skin tissue from 11% of the animals treated with FLCZ at 10 mg/kg per day, and from 20% of the animals treated with FLCZ at 20 mg/kg per day. The therapeutic efficacy of FLCZ was approximately equal to that of ITCZ administered at the same doses. These results suggest that FLCZ may be a useful treatment for dermatophytosis. Received: August 9, 1999 / Accepted: November 26, 1999     

Cocaine pharmacokinetics in the pregnant guinea pig

The pharmacokinetics of cocaine (COC) were studied during late gestation in guinea pigs. Clearance (Cl) was not dose-dependent and the average +/- S.D. was 59 +/- 16 ml/min/kg over the i.v. dose range of 2 to 12 mg/kg. Volume of distribution at steady state (Vdss), mean resident time (MRT) and elimination half-life (T1/2) were dose-dependent over this dose range with changes occurring between the 2 and the 4 mg/kg dose of COC. Vdss was 2.1 and 3.9 l/kg. MRT time was 42 and 57 min, and elimination T1/2 was 34 and 49 min at the 2 and 4 mg/kg dose, respectively. Cl and Vdss values after 2 to 20 mg/kg of COC s.c. were similar to those after i.v. administration, whereas MRT was significantly greater as a result of delayed absorption. Absorption of COC s.c. was nearly complete (84%) and had a T1/2 of 51 min. Benzoylecgonine (BE) and benzoylnorecgonine (NOR) were major and persistent metabolites of COC. Norcocaine was present after COC doses of 4 mg/kg or higher but could only be detected during the first 2 hr.     

Effect of endothelin-1 on guinea pig gallbladder smooth muscle in vitro.

The purpose of this study was to investigate the pharmacological activity of endothelin-1 (ET-1) on guinea pig gallbladder smooth muscle. Guinea pig gallbladder muscle strips were mounted in 10-ml siliconized organ baths containing Krebs' solution. After 1 hr of equilibration, ET-1 was added cumulatively. ET-1 induced slow-developing and long-duration contractile responses. The EC50 was approximately 10 nM. ET-1 was 5 times less potent than cholecystokinin (EC50, 2 nM), but 20 and 40 times more potent than carbachol (EC50, 200 nM) and histamine (EC50, 400 nM), respectively. The concentration-response curve to ET-1 was not affected by tetrodotoxin (0.1 microM) or by the muscarinic antagonist, atropine (10 microM). The neuronal N-type calcium channel blocker, omega-conotoxin (0.1 microM), had no significant effect on the ET-1 concentration-response curve. In contrast, the contractile effect to ET-1 was reduced markedly by removal of extracellular calcium or by the voltage-dependent calcium channel blockers nicardipine and diltiazem. Substitution of strontium (an inhibitor of intracellular calcium release) for Ca++ significantly reduced the response to ET-1. The cyclooxygenase inhibitor indomethacin had no significant effect on the contractile activity of ET-1. These finding suggest that ET-1 is a potent contractile stimulant of guinea pig gallbladder and that it acts directly on the smooth muscle. The activity depends on extracellular Ca++, suggesting involvement of Ca++ influx via the voltage-dependent Ca++ channel and on intracellular calcium.     

Analysis of preformed xenoreactive antibodies in the discordant guinea pig to rat model using a guinea pig fibroblast-like cell line

In the discordant guinea pig (gp) to rat model of xenotransplantation, circulating xenoreactive natural antibodies (XNA) recognizing gp antigens are usually determined by an ELISA using membrane extracts of gp platelets. We analysed the lung-derived, fibroblast-like cell line JH 4 to detect XNA by ELISA or immunoblot, which was compared to primary gp cells, i.e. platelets, liver- and spleen cells. All membrane extracts proved to be useful to detect rat XNA directed against gp antigens by ELISA. In general, IgM responses of Lewis or C6 deficient PVG rats (PVG/C6-) were higher as compared to IgG responses. However, we observed great inter-individual variabilities. The strongest IgM response of Lewis rat sera was observed when the JH 4 cell line or gp liver cells were used as antigen. JH 4 cells also showed the strongest xenoreactivity with sera from PVG/C6- rats. These data demonstrate that JH 4 cells prove useful as antigen source for XNA ELISA. In immunoblot, individual sera of the two different rat strains showed the same antigen patterns using a gp membrane extract of one particular cell type. However, the different gp cell types showed a distinct pattern of antigen expression. Whereas the JH 4 cells, platelets and spleen cells express xenoreactive proteins of the same size, a unique pattern of proteins was detected in liver cells.     

条件化噪声对强噪声所致豚鼠听力损伤的防护作用

目的　观察低强度实际工作环境噪声对相应的高强度噪声所致听力损伤是否有防护作用。方法　取杂色,耳廓反射正常,鼓膜完整的豚鼠30只,分为三组:条件化噪声组(CG),高强度噪声暴露组(HG),条件化噪声加高强度噪声暴露组(CHG)。所用低强度噪声(条件化噪声)为80dBSPL,高强度噪声为115dBSPL。每组动物实验前后进行听性脑干反应(ABR)测试,记录其反应阈。结果　给予条件化噪声暴露后,豚鼠的ABR反应阈与实验前相比无变化,而高强度噪声暴露和先条件化噪声再高强度噪声暴露后豚鼠的ABR反应阈均增高,但前者比后者的反应阈明显增高(P<0.001)。结论　低强度实际工作环境噪声对相应的高强度噪声所致豚鼠听力损伤具有一定防护作用。     

Effect of pulsed electromagnetic field stimulation on knee cartilage, subchondral and epyphiseal trabecular bone of aged Dunkin Hartley guinea pigs

It has been demonstrated that pulsed electromagnetic field (PEMF) stimulation has a chondroprotective effect on osteoarthritis (OA) progression in the knee joints of the 12-month-old guinea pigs. The aim of the present study was to discover whether the therapeutic efficacy of PEMFs was maintained in older animals also in more severe OA lesions.PEMFs were administered daily (6 h/day for 6 months) to 15-month-old guinea pigs. The knee joints (medial and lateral tibial plateaus, medial and lateral femoral condyles) were evaluated by means of a histological/histochemical Mankin modified by Carlsson grading score and histomorphometric measurements of cartilage thickness (CT), fibrillation index (FI), subchondral bone thickness (SBT) and epiphyseal bone microarchitecture (bone volume: BV/TV; trabecular thickness: Tb.Th; trabecular number: Tb.N; trabecular separation: Tb.SP). Periarticular knee bone was also evaluated with dual X-ray absorptiometry (DXA).PEMF stimulation significantly changed the progression of OA lesions in all examined knee areas. In the most affected area of the knee joint (medial tibial plateau), significant lower histochemical score (p < 0.0005), FI (p < 0.005), SBT (p < 0.05), BV/TV (p < 0.0005), Tb.Th (p < 0.05) and Tb.N (p < 0.05) were observed while CT (p < 0.05) and Tb.Sp (p < 0.0005) were significantly higher than in SHAM-treated animals. DXA confirmed the significantly higher bone density in SHAM-treated animals. Even in the presence of severe OA lesions PEMFs maintained a significant efficacy in reducing lesion progression.