舒胆通颗粒对实验动物胆汁分泌及胆囊平滑肌的影响

目的观察舒胆通（SDT）颗粒对大鼠胆汁分泌及胆囊平滑肌的影响。方法采用在体胆汁引流法,观察单次给予SDT对大鼠胆汁分泌以及总胆红素（TB）的影响;采用离体试验法观察SDT对豚鼠胆囊平滑肌条的直接作用及其对阿托品、酚妥拉明、苯海拉明、雷尼替丁的拮抗作用。结果SDT 5,10,20 g.kg^-1剂量能使大鼠给药后30－90 min时段胆汁分泌增加,但胆汁中TB水平无明显改变;终浓度为2.5×10^-4,5×10^-4,1×10^-3 mg.mL^-1的SDT能使离体豚鼠胆囊肌条张力增高、收缩频率加快、收缩幅度增加,并呈现明显的量效关系,其兴奋作用可被阿托品完全阻断,也可被酚妥拉明部分阻断,但不能被苯海拉明、雷尼替丁所阻断。结论SDT能增强胆囊平滑肌的兴奋性,促进胆汁分泌;其利胆作用可能主要经由胆碱能M受体介导,部分经由肾上腺素能α受体介导、而与组胺H1受体、前列腺素受体等途径无关。     

舒胆通颗粒对实验动物胆汁分泌及胆囊平滑肌的影响

目的 观察舒胆通(SDT)颗粒对大鼠胆汁分泌及胆囊平滑肌的影响。方法 采用在体胆汁引流法,观察单次给予SDT对大鼠胆汁分泌以及总胆红素(TB)的影响;采用离体试验法观察SDT对豚鼠胆囊平滑肌条的直接作用及其对阿托品、酚妥拉明、苯海拉明、雷尼替丁的拮抗作用。结果 SDT 5,10,20 g·kg^-1剂量能使大鼠给药后30~90 min时段胆汁分泌增加,但胆汁中TB水平无明显改变;终浓度为2.5×10^-4,5×10^-4,1×10^-3 mg·mL^-1的SDT能使离体豚鼠胆囊肌条张力增高、收缩频率加快、收缩幅度增加,并呈现明显的量效关系,其兴奋作用可被阿托品完全阻断,也可被酚妥拉明部分阻断,但不能被苯海拉明、雷尼替丁所阻断。结论 SDT能增强胆囊平滑肌的兴奋性,促进胆汁分泌;其利胆作用可能主要经由胆碱能M受体介导,部分经由肾上腺素能α受体介导、而与组胺H1受体、前列腺素受体等途径无关。     

黄体酮对豚鼠结肠平滑肌及细胞膜钙依赖的钾通道电流的影响

目的　观察黄体酮 (Progesterone)对豚鼠结肠平滑肌肌条和细胞的作用 ,借此探讨肠易激综合征 (IBS)的病理生理机制。方法　急性分离豚鼠结肠平滑肌肌条和单个平滑肌细胞。采用TD 112S型等张传感器测量肌条收缩与舒张的幅值、频率 ,并用Axopatch 1 D膜片钳放大器测全细胞模式下的单个平滑肌细胞大电导的钙离子依赖钾通道电流(BKCa)。结果　 6 4 8μmol·L-1黄体酮可抑制结肠带肌条的收缩 (0 1792± 0 0 873) g(n =6 ,P <0 0 5 ) ,而低浓度黄体酮仅抑制结肠环行平滑肌肌条的收缩 (16 2pmol·L-10 2 36 0g± 0 15 78g ,n =6 ,P <0 0 5 ;1 6 2nmol·l-10 4 332 g±0 2 111g ,n =6 ,P <0 0 1;3 2 4nmol·l-1部分肌条完全抑制P <0 0 1) ,其效应呈剂量依赖的趋势。细胞实验中 12 96μmol·L-1的黄体酮可抑制BKCa的幅值约 6 0 %± 17% (n =10 ,P <0 0 1) ,而灌流液含 5 μmol·L-1尼卡地平 (nicardip ine)时抑制BKCa的作用不明显。结论　高浓度黄体酮对纵行和环行平滑肌均有抑制作用 ,而低浓度主要抑制环行平滑肌的收缩 ,作用机制与减少细胞外钙离子内流及抑制BKCa有关 ,这种作用可部分解释在临床上IBS妇女患病更普遍的现象 ,对女性IBS患者的激素治疗有一定的提示作用     

干酪菌发酵产物对豚鼠离体回肠平滑肌收缩功能的影响

目的 观察干酪菌发酵产物对豚鼠离体回肠平滑肌收缩功能的影响。方法采用豚鼠离体回肠平滑肌标本,观察加入干酪菌发酵产物前后肌紧张的变化以及加入几种受体阻断剂对其药效的影响。结果 干酪菌发酵产物能提高豚鼠离体回肠平滑肌肌紧张,且呈剂量-效应依赖关系,组织胺H1受体阻断剂苯海拉明能阻断其兴奋作用。结论 干酪菌发酵产物能提高豚鼠离体回肠平滑肌肌紧张,其作用途径与组织胺H1受体有关。     

大黄素对豚鼠胆囊平滑肌L型钙电流的调节

目的研究大黄素对豚鼠胆囊肌条收缩及L型钙电流的调节。方法取成年豚鼠,分离胆囊肌条,使用张力传感器记录胆囊肌条的收缩活动。采用酶消化法急性分离豚鼠胆囊平滑肌细胞,使用全细胞膜片钳技术记录L型钙电流。结果预先加入硝苯地平,大黄素对胆囊肌条的收缩效应明显减弱。大黄素增加胆囊平滑肌细胞L型钙电流,呈浓度依赖性。与正常对照组相比,10μmol·L-1大黄素明显增强+10mV时L型钙电流幅度的(45.2±2.26)%(P<0.05)。预先加入PKC抑制剂十字孢碱,大黄素对钙电流的调节基本被抑制。结论大黄素可通过PKC途径增强胆囊平滑肌L型钙电流,从而促进胆囊平滑肌收缩。     

雷尼替丁和西咪替丁对大鼠结肠平滑肌条收缩活动的影响(英文)

通过大鼠离体结肠平滑肌条实验 ,观察雷尼替丁 ( 0 .0 2 ,0 .2 ,2和 10mmol·L- 1)和西咪替丁 ( 0 .0 .8和 4mmol·L- 1)对结肠收缩活动的影响 .结果表明 :雷尼替丁和西咪替丁增加结肠头端环行肌和结肠尾端纵行肌的平均收缩幅度以及结肠尾端环行肌的运动指数 ,减小结肠头端纵行肌的平均收缩幅度 ,并均有一定的剂量效应关系 ;雷尼替丁增加结肠头端纵行肌的静息张力和结肠尾端纵行肌的收缩频率 ,西咪替丁则降低结肠肌条的收缩频率 .阿托品( 0 .0 1μmol·L- 1)部分阻断雷尼替丁 ( 0 .2mmol·L- 1)对结肠肌条的兴奋作用 ,但不影响西咪替丁 ( 0 .8mmol·L- 1)的作用 ;六甲溴铵 ( 10 μmol·L- 1)不影响雷尼替丁和西咪替丁对结肠肌条的作用 .提示 ,雷尼替丁和西咪替丁对结肠肌条主要表现兴奋作用 ,雷尼替丁对结肠的作用与M受体有关     

黄体酮对离体豚鼠呼吸道平滑肌的作用

黄体酮能明显抑制由乙酰胆碱、组织胺和5—羟色胺所致的离体豚鼠气管、肺条平滑肌的收缩反应,对由5—羟色胺诱发的气管平滑肌依内钙释放引起的！相收缩有非常显著的抑制作用,并能抑制致敏豚鼠气管平滑肌schultZ—Dale反应.关键词黄体酮,维拉帕米,慢反应物质,呼吸道平滑肌     

芒果苷利胆作用及对胆囊平滑肌痉挛的影响

目的：探讨芒果苷利胆作用及对胆囊平滑肌痉挛的影响.方法：利用胆管引流法测定芒果苷对大鼠胆汁的流量及成分的影响;通过对豚鼠胆囊肌条的收缩试验观察芒果苷对乙酰胆碱所致胆囊平滑肌痉挛的影响.结果：芒果苷4.74×10-5 mol·kg-1剂量组可显著提高大鼠的胆汁流量,显著提高胆汁中胆红素浓度（P ＜0.01）;2.37×10-5 mol·L-1剂量组可显著抑制由乙酰 胆碱引起的豚鼠胆囊痉挛（P＜0.01）.结论：芒果苷具有利胆作用,可缓解乙酰胆碱引起胆囊痉挛.     

雌二醇对离体和在体气管平滑肌收缩活动的抑制作用

目的:研究雌二醇对离体和在体气管平滑肌收缩的作用.方法:(1)将家兔离体气管平滑肌条置于装有Krebs液的肌槽中温育,并通入95％O_2和5％CO_2的混合气体.二导记录仪记录肌条的等长张力.(2)测量肌注雌二醇(1mg/kg)前后乙酰胆碱和组胺引发豚鼠哮喘的潜伏期.结果:(1)雌二醇(100μmol/L)对乙酰胆碱和氯化钾诱发的收缩有明显的舒张作用(舒张百分比分别为39％±5％和45％±19％).其作用可被蚓哚美辛和亚甲蓝部分阻断(26％±8％和28％±13％),但不能被L-NNA、心得安和去除上皮所影响(舒张百分比分别为38％±10％,40％±15％,37％±8％).雌二醇能使乙酰胆碱及氯化钙的量效曲线明显右移(pD_2~′值分别为3.98和4.75).另外,雌二醇可明显抑制乙酰胆碱引起的第Ⅰ时相性收缩,对氯化钙引起的第Ⅱ时相性的收缩无明显影响.(2)肌注雌二醇(1mg/kg)可使豚鼠的引喘潜伏期明显延长.结论:(1)雌二醇对兔离体气管平滑肌的作用是非上皮依赖性的,与抑制电压依赖性钙通道和细胞内钙从内质网的释放有关,还部分与cGMP介导的松弛途径及刺激气道平滑肌释放前列腺素类物质有关,但与β-肾上腺素能受体介导的舒张无关.(2)雌二醇可明显舒张豚鼠在体气管平滑肌.     

大黄素对豚鼠结肠收缩性的影响及其机制的研究

目的研究大黄素对豚鼠离体远端结肠平滑肌收缩活动的影响及其可能机制。方法急性分离豚鼠远端结肠平滑肌,采用生理记录仪记录不同浓度大黄素对远端结肠收缩的影响;木瓜蛋白酶消化分离豚鼠近端结肠平滑肌细胞,采用全细胞膜片钳技术记录钾电流。结果不同浓度的大黄素（1～50μmol.L-1）对豚鼠远端结肠具有双向调节作用,且其效应呈剂量依赖的趋势1～10μmol.L-1大黄素可浓度依赖性地增强豚鼠远端结肠平滑肌的收缩10μmol.L-1浓度时,大黄素的作用达到平台期。当大黄素的浓度大于10μmol.L-1时,逐渐呈现明显的抑制作用,且其抑制作用与浓度正相关10μmol.L-1硝苯地平孵育肌条后,大黄素不能增强肌条的收缩。大黄素（1～30μmol.L-1）浓度依赖性地抑制豚鼠近端结肠平滑肌细胞钾电流。结论大黄素增强豚鼠结肠的收缩作用可能与L-型钙通道及钾通道有关。     

Diminished inibitory action of ethanol on the contraction of gallbladder isolated from chronically ethanol-fed Guinea pigs

Ethanol is known to decrease the gallbladder contractility. The purpose of this study was to clarify the mechanism of tolerance to the inhibitory action of ethanol on the gallbladder contractility. Male guinea pigs were fed ethanol (3%) or calorie-matched sucrose in the drinking water for 4 weeks. Then, the gallbladder was isolated, and its isometric tension was measured. The contractile responses to KCl, BAY K8644, histamine, and phorbol 12,13-dibutyrate in the normal medium were not different between the gallbladder strips from ethanol-fed and control guinea pigs. Ethanol at 25 mmol/l in vitro did not affect the contractile responses to KCl and BAY K8644 in the gallbladder strips from both ethanol-fed and control guinea pigs. On the other hand, ethanol at 25 mmol/l in vitro significantly inhibited the contractile responses to histamine and phorbol 12,13-dibutyrate in the gallbladder strips from the control guinea pigs, but it did not affect the contractile response to histamine and significantly augmented that to phorbol 12,13-dibutyrate in the strips from the ethanol-fed guinea pigs. Diphenhydramine, a selective H(1) receptor antagonist, abolished the histamine contraction in gallbladder strips from both control and ethanol-fed guinea pigs, while cimetidine, a selective H(2) receptor antagonist, did not affect histamine contraction, implying that histamine-induced contraction of guinea pig gallbladders is mediated only by H(1) receptors. Verapamil (1 micromol/l) completely inhibited the phorbol 12,13-dibutyrate-induced contraction of the strips from both ethanol-fed and control guinea pigs. The histamine-induced contraction was partly inhibited in the absence of Ca(2+) in the medium. In the gallbladder strips from both ethanol-fed and control guinea pigs, ethanol at 25 mmol/ in vitro did not affect the histamine-induced contraction in the absence of extracellular Ca(2+). Tolerance to the inhibitory action of ethanol developed selectively on contractile responses to histamine and phorbol 12,13-dibutyrate. Chronic ethanol administration produces tolerance to in vitro gallbladder contractility mediated by the Ca(2+) entry through L-type Ca(2+) channels linked with protein kinase C activation.     

Relaxant effect of aspirin-like drugs on isolated guinea pig tracheal chain.

The interrelation of the inhibitory effect of aspirin-like drugs on the resting tonus of tracheal chain in guinea pigs, arachidonic acid-induced contraction in rat stomach fundus strips and bradykinin-induced bronchoconstriction in guinea pigs in vivo was investigated. All the drugs tested produced a dose-related inhibitory action on the resting tonus of the tracheal chain in comparatively low doses. Diclofenac was the most potent of all the drugs and was equal in activity to isoproterenol, followed in descending order by flufenamic acid, mefenamic acid, indomethacin, ibuprofen, phenylbutazone, oxyphenbutazone and aspirin. These aspirin-like drugs also inhibited arachidonic acid-induced contraction in rat stomach fundus strips. A highly significant correlation was observed between the potency of inhibition of the arachidonic acid-induced contraction and the relaxant effect on the tracheal chain. Moreover, the drugs antagonized bradykinin-induced bronchoconstriction in guinea pigs in vivo and the order of potency roughly paralleled that of the tracheal chain. These results suggest that the aspirin-like drugs produce a reduction in resting tonus of the isolated guinea pig tracheal chain by inhibition of intramural biosynthesis of prostaglandin endoperoxides.     

乳舒片对乳腺增生模型豚鼠的实验研究

目的:观察乳舒片对乳腺增生模型豚鼠的治疗作用。方法:采用苯甲酸雌二醇联合黄体酮肌注的方法.复制豚鼠乳腺增生模型,用乳舒片治疗30 d,测定豚鼠乳头直径及高度;测定豚鼠血清雌二醇(E_2)和孕酮(P)的含量。结果:乳舒片组豚鼠乳腺高度及乳腺直径均较模型对照组明显缩小,显著降低豚鼠血清E_2和P水平。结论:乳舒片对豚鼠乳腺增生痛有较好的疗效。     

Ranitidine but not famotidine releases acetylcholine from the guinea pig myenteric plexus

The effects of the histamine H2-receptor antagonists ranitidine and famotidine on acetylcholine release have been studied in the guinea pig myenteric plexus longitudinal muscle preparation incubated with [3H]-choline. Ranitidine (3 x 10(-5)-3 x 10(-4) M) dose-dependently increased the resting release of acetylcholine and that evoked by electrical stimulation. The effect was present only in strips perfused with 10(-5) M physostigmine. The effect of ranitidine was inhibited by tetrodotoxin and hexamethonium. Famotidine (10(-5)-3 x 10(-4) M) was totally ineffective in modifying both the resting release and that evoked by field stimulation. Ranitidine did not antagonize the inhibitory effect of oxotremorine, which specifically activates negative feedback mechanisms via presynaptic muscarinic receptors.     

花生四烯酸、二十碳五烯酸及二十二碳六烯酸对兔主动脉条张力的影响

外源性AA引起兔动脉条收缩,呈剂量依赖性;EPA抑制AA收缩血管亦呈浓度依赖性;DHA对AA收缩血管作用无明显影响。破坏血管内皮后AA收缩血管作用大为减弱,EPA抑制AA收缩血管作用也几乎消失。吲哚美辛能阻断AA收缩兔主动脉条的作用。兔主动脉6-keto-PGF_1α、TXB₂及其比值随AA浓度升高而增加,低剂量EPA对前列腺素类代谢无明显影响,较大剂量时则降低上述指标。     

Involvement of endothelin and nitric oxide in cyclosporine A-induced contractions in guinea pig isolated gallbladder strips.

The involvement of endothelin (ET), ET(A) receptors and nitric oxide (NO) in the contractions induced by cyclosporine A (CyA) were investigated in guinea pig isolated gallbladder strips. Both BQ-123, a selective ET(A) receptor antagonist, and phosphoramidon, an ET converting enzyme inhibitor, inhibited the contractile responses to the parenteral and oral CyA preparations, whereas l-NOARG, a NO synthase inhibitor, potentiated these contractions. Additionally, the pattern of the concentration-dependent contractions in response to ET-1 was similar to that of CyA preparations in gallbladder strips. Both bosentan, a non-selective ET receptor antagonist, and BQ-123 inhibited the ET-1-induced contractions. These findings suggest that an ET-1-mediated mechanism contributes to the contractile response to CyA preparations in guinea pig isolated gallbladder strips. ET(A) receptor activation is likely to be involved in this process. We also speculate that CyA-induced stimulation of NO production might act as a counter-regulatory mechanism in the effect of CyA preparations in this tissue.     

Inhibitory effects of OKY-046 on spasmogen-induced bronchoconstrictions in sensitized and non-sensitized guinea pigs

We examined the effect of thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on bronchoconstriction induced by antigen and various spasmogenic mediators in guinea pigs in vivo. Further, inhibitory activities of OKY-046 on contractions of isolated tracheae and lung parenchymal strips induced by various contractile agents were also investigated in vitro. OKY-046, but not indomethacin, significantly inhibited antigen-induced bronchoconstriction in a dose-dependent manner. Moreover, OKY-046 attenuated bronchoconstrictions induced by peptide leukotrienes (LTs) and platelet activating factor (PAF), but not those by histamine, prostaglandin D2 (PGD2) and STA2 (a stable TXA2 mimetic agent). Although contractile responses induced by spasmogens such as peptide LTs, PAF and histamine were not influenced by OKY-046 in isolated tracheae, OKY-046 elicited significant and concentration-dependent inhibitions against contractile responses induced by peptide LTs and PAF in isolated lung parenchymal strips. These results suggest the possible involvement of TXA2 in the development of anaphylactic bronchoconstriction in sensitized guinea pigs.     

The role of nitric oxide in the electrical field stimulation-induced contractions of sphincter of oddi and gallbladder strips in Guinea pigs

The aim of this study was to investigate the modulatory role of nitric oxide (NO) in the electrical field stimulation (EFS)-induced contractions of isolated sphincter of Oddi (SO) and gallbladder strips from guinea pigs. EFS was used to activate the intrinsic nerves in SO and gallbladder strips. EFS produced frequency-dependent biphasic contractile responses in the SO strips. A smaller contraction, "on response", occurred during EFS, which was followed by a bigger contraction, "off response". Both responses were completely and irreversibly abolished by tetrodotoxin (TTX) (10(-6) M). Atropine (10(-6) M) inhibited the "on response", but not the "off response". EFS produced frequency-dependent monophasic contractile responses in gallbladder strips, which were completely and irreversibly abolished by TTX (10(-6) M) and atropine (10(-6) M). A nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (10(-4) M and 3 x 10(-4) M, in SO and gallbladder strips, respectively), significantly increased all EFS-induced contractions of SO and gallbladder strips. L-Arginine, but not D-arginine reversed the effect induced by the NOS inhibitor, at all frequencies, in both strips. These results suggested that NO released from nitrergic nerve endings might play a regulatory role in the cholinergic neurotransmission of guinea pig SO and gallbladder strips. The "off response" in he SO preparations might be a rebound increase that was modulated by the nonadrenergic, noncholinergic inhibitory mediator NO.     

Neurokinin A-induced guinea pig gallbladder contraction: Potential mechanism of action

The present study was performed to examine the mechanism of action of neurokinin A (NKA) on guinea pig gallbaldder smooth muscle. Muscle strips were prepared and mounted in 10 mL tissue bath containing Krebs' solution under 1 g tension. NKA induced a concentration-dependent increase in gallbladder muscle tension and reached a maximal response at 1 μM. The EC₅₀ value was approximately 30nM. Preincubation of the muscle strips with neurotoxins, tetrodotoxin (1 μM), or omega-conotoxin (0.1 μM) had no effect on the NKA contractile response. NKA-induced gallbladder contractions were insensitive to cyclooxygenase inhibitors (5 μM) piroxicam and indomethacin. In contrast, the calcium channel blockers verapamil and diltiazem (0.1–1 μM) significantly blocked the contractile response to NKA. The intracellular calcium chelator BAPTA/AM had no significant effect on NKA activity. The removal of extracellular calcium, however, completely abolished the contractile response of NKA. These data suggest that NKA has a direct contractile effect on guinea pig gallbladder smooth muscle, which is independent of prostaglandin release. The primary source of calcium involved in mediating the NKA contractile response is the extracellular pool, suggesting that NKA might act via activation of L-type voltage-operated calcium channels to mediate its action. © 1992 Wiley-Liss, Inc.     

4-Hydroxyandrostenedione is not an aromatase inhibitor in the neonatal guinea pig

One-day-old newborn guinea pigs were treated with 4-hydroxyandrostenedione (50 mg/kg body weight/day) for 5 or 12 consecutive days. This compound did not decrease unconjugated or sulfoconjugated estradiol and estrone levels in the plasma or in the uterine tissue itself. It also did not have any effect on uterine wet weight or the estrogen and progesterone receptor concentrations in the uterus. Moreover, progesterone receptor synthesis which is maintained when neonatal uteri are placed in organ culture conditions for 2 days was not affected by the 4-hydroxyandrostenedione treatment.