M_3受体激动剂对大鼠和家兔心脏血流动力学的影响

目的　研究胆碱对大鼠和家兔心脏M3 受体的激动作用及其引起的血流动力学改变。方法　经右颈总动脉插管入左心室 ,用八导生理记录仪测定大鼠和家兔血流动力学参数。结果　iv胆碱 10mg·kg-130s后 ,大鼠的心率 (HR)比基础值明显降低 ,10min后恢复。±dp/dtmax和LVSP于给药 10min后明显降低。上述抑制作用可被选择性M3 受体阻断剂 4 DAMP 0 12mg·kg-1所对抗。家兔iv胆碱 5mg·kg-1后 1min ,心率明显降低 ,此作用可被 4 DAMP所对抗。±dp/dt,LVSP亦有下降趋势 ,但无统计学差异。M3 受体阻断剂 4 DAMP对大鼠和家兔血流动力学无明显影响 ,但预先给药可阻断胆碱引起的血流动力学变化。结论　胆碱通过激动心脏M3 受体产生负性肌力和负性频率作用     

毛果芸香碱对哇巴因诱发豚鼠心律失常的保护作用

目的 观察毛果芸香碱对实验性心律失常模型的影响.方法 以哇巴因制备实验性动物心律失常模型,观察毛果芸香碱(0.2 mg· kg-1)的干预作用.结果 毛果芸香碱能明显延长哇巴因引起豚鼠出现心律失常后的存活时间(P＜0.05).毛果芸香碱的作用可被M3受体阻断剂4-DAMP(4-二苯乙酰氧-N-甲基哌啶甲碘化物)完全逆转.结论 毛果芸香碱通过激动豚鼠心肌M3受体而具有对抗哇巴因诱发豚鼠心律失常的作用,提示毛果芸香碱有良好的抗心律失常作用.     

M3受体激动剂对大鼠和家兔心脏血流动力学的影响

目的　研究胆碱对大鼠和家兔心脏M₃受体的激动作用及其引起的血流动力学改变。方法　经右颈总动脉插管入左心室,用八导生理记录仪测定大鼠和家兔血流动力学参数。结果　iv胆碱10mg·kg^-130s后,大鼠的心率(HR)比基础值明显降低,10min后恢复。±dp/dt max和LVSP于给药10min后明显降低。上述抑制作用可被选择性M3受体阻断剂4-DAMP0.12mg·kg^-1所对抗。家兔iv胆碱5mg·kg^-1后1min,心率明显降低,此作用可被4-DAMP所对抗。±dp/dt,LVSP亦有下降趋势,但无统计学差异。M3受体阻断剂4-DAMP对大鼠和家兔血流动力学无明显影响,但预先给药可阻断胆碱引起的血流动力学变化。结论　胆碱通过激动心脏M3受体产生负性肌力和负性频率作用。     

M_3受体激动剂对豚鼠心室肌细胞L型钙通道的影响

目的研究M3受体激动剂胆碱对豚鼠心室肌细胞L型钙通道的影响。方法应用全细胞膜片钳技术记录M3受体激动剂胆碱对豚鼠单个心室肌细胞L型钙通道电流(ICa-L)的影响;采用激光扫描共聚焦技术观察细胞内钙离子的变化。结果应用10 mmol.L-1胆碱使豚鼠心室肌细胞ICa-L密度从(9.02±0.82)pA/pF减少到(5.61±0.55)pA/pF(n=4,P<0.01),5 nmol.L-14-DAMP能够使其恢复至(8.12±0.65)pA/pF(n=4,P<0.01);10 mmol.L-1胆碱抑制KCl除极诱导的心肌细胞内钙的升高,从(2.76±0.05)降至(1.37±0.05)倍(n=8,P<0.01),5 nmol.L-14-DAMP可以阻断该作用(n=8,P<0.01)。结论M3受体激动剂胆碱通过延长L型钙通道激活过程而明显抑制ICa-L,减少细胞外的钙离子内流,降低心肌细胞内钙,从而发挥抗心律失常作用。     

各种心律失常模型中心肌M3受体表达与心律失常的关系

目的：探讨各种心律失常模型心肌M3受体的变化及其与心律失常的关系。方法：30只大鼠随机分为3组，乌头碱，氯化钡和缺血组。分别注射乌头碱、氯化钡及结扎冠脉诱发大鼠心律失常，记录lh心电图的变化。Western blot检测心肌M3受体的表达（24h）。结果：各组均可诱发心律失常，乌头碱组心律失常和室性心动过速的持续时间较其余两个模型组明显延长。Western blot显示，各组模型大鼠心肌M3受体的表达均上调，分别为正常组的2．3，1．4和1．3倍，其中乌头碱组心肌M3受体的含量明显升高。心肌M3受体蛋白的表达和心律失常的持续时间呈正相关关系。结论：心律失常能诱导心肌M3受体的表达上调，且不同心律失常模型心肌M3受体上调的幅度不同，其机制可能和心律失常的严重程度呈正相关关系。     

胆碱对乌头碱和哇巴因所诱发的心律失常的保护作用

目的探讨胆碱对乌头碱和哇巴因所诱发的心律失常的保护作用。方法大鼠和豚鼠分别注射乌头碱或哇巴因制备心律失常模型,观察预先给予低剂量(5 mg.kg-1)和高剂量(20 mg.kg-1)的胆碱对心律失常的保护作用。结果给予胆碱可明显对抗乌头碱或哇巴因所诱发的心律失常,表现为明显延迟心律失常的出现,推迟动物死亡时间等。高剂量胆碱对心律失常的保护作用优于低剂量。结论胆碱对心律失常具有保护作用,高剂量的作用优于低剂量。     

胆碱对离体大鼠心肌缺血/再灌注损伤的保护作用

目的观察胆碱对离体大鼠心肌缺血/再灌注损伤的影响。方法采用Langendorff灌注系统,建立离体大鼠全心缺血/再灌注损伤模型。观察胆碱对复灌后冠脉流量、心肌组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和心肌梗死面积的影响。结果胆碱可明显增加缺血/再灌注后1、5、10min的冠脉流量,减少心肌组织MDA含量、提高SOD活性,缩小心肌梗死面积,与模型组比较差异均有显著性(P<0.05)。上述作用可部分的被选择性M3受体阻断剂4-di-phenylacetoxy-N-methylpiperidine-methiodide(4-DAMP)所逆转。结论胆碱对离体大鼠心肌缺血/再灌注损伤具有保护作用。     

毛果芸香碱对心律失常保护作用的研究

目的观察毛果芸香碱对动物心律失常模型的作用。方法分别以乌头碱和氯化钡制造动物心律失常模型,观察毛果芸香碱(0.2mg/kg)对心律失常的影响。结果毛果芸香碱可明显延迟乌头碱引起的大鼠室性心律失常的出现(P<0.05);延长大鼠出现心律失常后的存活时间(P<0.05);毛果芸香碱可明显延迟氯化钡引起的大鼠双向室性心律失常的出现(P<0.05)、缩短大鼠心律失常的持续时间(P<0.05)。4-DAMP可完全拮抗毛果芸香碱诱导的心律失常。结论毛果芸香碱通过激动大鼠心肌M3受体而产生对抗乌头碱和氯化钡诱发大鼠心律失常的作用。     

组胺H_3受体激动剂与拮抗剂

组胺Ｈ_３受体激动剂与拮抗剂罗晓星，谭月华（第四军医大学药理教研室，西安７１００３２）组胺受体药理学研究方面曾经有过两次重大突破：１９３７年Ｂｏｖｅｔ首先发现了经典的＂抗组胺药＂（亦即现在的Ｈ１受体拮抗剂）［１］，１９７２年Ｂｌａｃｋ创制成功Ｈ２受体?..     

毛果芸香碱对实验性心律失常的保护作用

目的：观察毛果芸香碱对实验性心率失常的影响。方法：分别以乌头碱，氯化钡和哇巴因制备实验性动物心律失常模型，观察毛果芸香碱的干预作用。结果：毛果芸香碱可显著延迟乌头碱引起的大鼠室性心律失常的出现（P〈0．05），延长出现心律失常后的存活时间（P〈0．05）；能明显延迟氯化钡引起的大鼠双相室性心律失常的出现（P〈0．01），缩短心律失常的持续时间（P〈0．01）；能显著延长哇巴因引起豚鼠出现心律失常后的存活时间（P〈0．05）。毛果芸香碱的上述作用可被M3受体阻断荆4-DAMP完全逆转。结论：毛果芸香碱具有对抗乌头碱和氯化钡诱发大鼠，哇巴因诱发豚鼠心律失常的作用，提示其具有良好的抗心律失常作用；毛果芸香碱通过激动大鼠和豚鼠心肌M3受体而产生抗心律失常的作用。     

碘化N-正丁基氟哌啶醇对抗氯化钡引起心律失常的作用

目的研究碘化N-正丁基氟哌啶醇对抗BaCl2引起心律失常的作用.方法采用氯化钡诱导的心律失常动物模型,观察碘化N-正丁基氟哌啶醇对抗BaCl2引起心律失常的作用.结果碘化N-正丁基氟哌啶醇(0.5、1、2、4 mg/kg)可剂量依赖的减少氯化钡诱发心律失常的发生率,缩短心律失常的持续时间.结论碘化N-正丁基氟哌啶醇具有明显的对抗BaCl2引起心律失常的作用.     

碘化N-正丁基氟哌啶醇对抗氯化钡引起心律失常的作用

目的研究碘化N-正丁基氟哌啶醇对抗BaCl2引起心律失常的作用。方法采用氯化钡诱导的心律失常动物模型,观察碘化N-正丁基氟哌啶醇对抗BaCl2引起心律失常的作用。结果碘化N-正丁基氟哌啶醇(0.5、1、2、4mg/kg)可剂量依赖的减少氯化钡诱发心律失常的发生率,缩短心律失常的持续时间。结论碘化N-正丁基氟哌啶醇具有明显的对抗BaCl2引起心律失常的作用。     

Protective effects of pomegranate peel against hematotoxicity,chromosomal aberrations,and genotoxicity induced by barium chloride in adult rats

Context Pomegranate peel (PP) has health benefits including antibacterial, antioxidant, anti-inflammatory, and antimutagenic properties.

Objective This study investigated the biochemical composition and protective effects of PP against hematotoxicity and genotoxicity induced by barium chloride (BaCl₂) in adult rats.

Materials and methods Adult Wistar rats were divided into four groups of six each: control, barium (67?ppm via drinking water), PP (5% via diet), and their combination during 21 d. Oxidative stress was determined by MDA, AOPP, and antioxidant status: CAT, GPx, GSH, Vit C. Osmotic fragility (OF), chromosomal aberrations (CAs), and micronucleus (MN) assays were also studied.

Results PP showed a rich composition of antioxidant compounds. DPPH test found IC₅₀ value=?5.3?μg/mL and a high polysaccharides content (315?±?5?mg/g of extract). In vivo study showed a decrease in red blood cells (70%) and platelet counts (46%), hemoglobin content (8%), hematocrit percent (7%), and an 80% increase of white blood cells in Ba-treated rats. A reduction in antioxidant status: catalase, glutathione peroxidase activities, glutathione, and vitamin C levels by 31, 21, 28, and 29%, respectively, and an increase in MDA (46%) and AOPP levels (72%) were also observed compared with controls. BaCl₂-treatment showed a significant increase in the frequencies of total chromosomal aberrations with abnormal metaphases and micronucleus in bone-marrow cells. Oxidative stress induced by BaCl₂ might be the major cause for chromosomal abnormalities leading to DNA damage.

Discussion and conclusion A decrease in hematotoxic and genotoxic effects induced by PP is due to its powerful antioxidant capacity.     

腺苷对心肌缺血再灌注心律失常的保护作用

目的观察腺苷对在体大鼠心肌缺血／再灌注（I／R）心律失常的影响，探讨其可能的作用机制。方法健康Wister大鼠36只，随机分成3组假手术组、对照组、腺苷组，每组12只。开胸结扎左冠状动脉前降支30分钟，再灌注45分钟．制作大鼠心肌缺血／再灌注损伤模型。假手术组只穿线不结扎冠状动脉。腺苷组于结扎前1分钟给予腺W（0．4ml／kg）左心室内注入，对照组给予等量生理盐水左心室内注入。观察再灌注室性心动过速（VT）、室颤（VF）发生率和死亡率；检测左心室心肌组织超氧化物歧化酶（SOD）及丙二醛（MDA）含量。结果①腺苷组大鼠再灌注VT及VF发生率及死亡率均较对照组明显降低（P〈0.01）；②与对照组比较，腺苷组大鼠SOD活力提高（P〈0．05），而MDA生成量明显减少（P〈0．01）。结论心肌缺血再灌注可导致缺血心肌进一步损伤，腺苷具有抗大鼠I／R心律失常作用，可能与抑制缺血再灌注氧自由基的产生有关。     

Glucocorticoids modulate behavioral effects induced by dopaminergic agonists in rats

Studies showing the presence of glucocorticoids, and their binding sites in the central nervous system indicate that these hormones may affect central neurotransmission. Both, dopaminergic brain system and glucocorticoids are considered to be involved in certain psychopathological conditions in humans, including depression, addiction or schizophrenia. The present study aimed to investigate the influence of glucocorticoids on dopamine agonists-induced stereotyped behavior and locomotor hyperactivity in rats. The results of the experiment demonstrate that prior to administration of prednisolone (4, 6, 10 or 20 mg/kg) or dexamethasone (4 or 8 mg/kg) intensified and prolonged the stereotypy induced by apomorphine (1 mg/kg sc) or amphetamine (2 mg/kg ip). The effect of dexamethasone was more potent. Amphetamine (0.4 mg/kg)- or amantadine (50 mg/kg)-induced locomotor hyperactivity was significantly reduced in rats pretreated with dexamethasone at a dose of 8 mg/kg or 4 mg/kg. Our observations suggest that exogenous glucocorticoids may enhance the activity of the dopaminergic agonists in the striatum but reduce it in the mesolimbic system of rats.     

Protective effects of D,L-carnitine against arrhythmias induced by lysophosphatidylcholine or reperfusion

Electrophysiological effects of lysophosphatidylcholine (50 or 100 microM) and D,L-carnitine (100 microM) were studied under control conditions and in response to simulated ischaemia and reperfusion using the superfused right ventricular free wall preparation from the guinea pig heart. Lysophosphatidylcholine, 100 microM, induced a significant depolarization of the maximum diastolic potential (MDP) in the epicardium, as well as the development of ventricular premature beats, salvos and ventricular tachycardia. Both coupled beats and abnormal automaticity were observed in lysophosphatidylcholine (100 microM)-treated preparations. Carnitine (100 microM) alone had no effect on preparations superfused with normal Tyrode solution. However, it delayed the time to onset and reduced the cumulative duration of lysophosphatidylcholine-induced arrhythmias (P less than 0.05). The incidence of lysophosphatidylcholine-induced abnormal automaticity and salvos was also significantly decreased in the presence of carnitine. Twenty minutes of simulated ischaemia caused depolarization of MDP as well as prolongation followed by block of transmural conduction. Lysophosphatidylcholine (100 microM) did not alter this response however, carnitine significantly reduced ischaemia-induced depolarization in the epicardium. All control preparations developed arrhythmic activity during 30 min of reperfusion. Carnitine accelerated recovery of MDP in the epicardium upon reperfusion, prolonged the time to onset of arrhythmic activity and reduced both its cumulative duration and incidence. In contrast, reperfusion in the presence of lysophosphatidylcholine (100 microM) significantly increased the incidence of arrhythmic activity. Carnitine exerted only minimal antiarrhythmic action when preparations were exposed to reperfusion in the presence of lysophosphatidylcholine. In conclusion, this study demonstrates that carnitine can modify various cellular mechanisms of arrhythmia induced by lysophosphatidylcholine or by reperfusion but is much less effective when lysophosphatidylcholine and reperfusion are combined.     

Discriminative stimulus effects of putative D3 dopamine receptor agonists in rats

Three separate groups of rats were trained to discriminate the putative D3 dopamine receptor agonists (+/-)-7-hydroxydipropylaminotetralin (7-OH-DPAT) (0.03 mg/kg), PD 128,907 (1.0 mg/kg) and quinpirole (0.03 mg/kg) from saline. Food was presented after each 10 (7-OH-DPAT and PD 128,907) or 20 (quinpirole) consecutive responses on one lever after administration of the training drug, and the other lever after the administration of saline. Once stable performances were obtained, the effects of various doses of several dopaminergic agonists were assessed during test sessions in which responses on either lever were reinforced. The substitution tests were conducted to determine if differences in potencies would be obtained, which would be suggestive of differences in the mechanisms underlying the discriminative effects of the training drugs. Non-selective agonists with activity at both D2 and D3 dopamine receptors (D2-like agonists) substituted for each of the three training drugs. In addition, the selective D2 dopamine receptor agonist U91356A also generalized to both 7-OH-DPAT and PD 128,907. The potencies of the D2-like agonists in substituting for each training drug were highly correlated with potencies in substituting for the others. SKF 82958 and SKF 81297, agonists with selectivity for D1 and D5 dopamine receptors (D1-like agonists), partially substituted for 7-OH-DPAT but not PD 128,907. The D1-like partial agonist SKF 38393 did not substitute for any of the training drugs for which it was tested. Cocaine produced intermediate substitution in 7-OH-DPAT- and PD 128,907-trained subjects and did not substitute at all in quinpirole-trained subjects. The dopamine D1-like antagonist SCH 39166 (0.001-0.03 mg/kg) did not alter the discriminative stimulus effects of PD 128,907, whereas the D2-like dopamine antagonist spiperone (0.001-0.1 mg/kg) produced at the highest dose an insurmountable antagonism of the discriminative effects of PD 128,907. In contrast, there was no appreciable antagonism of the effects of PD 128,907 on response rates. The data collected are consistent with a distinction between the effects of each of these training drugs and the indirectly acting agonist cocaine. Further, these data indicate that there are differences in the mechanisms underlying the discriminative effects of PD 128,907 and its effects on response rates. Moreover, these data indicate that each of the training drugs is distinct from drugs acting through D1 dopaminergic mechanisms. However, there were no data that clearly distinguished these training drugs from each other or from drugs acting through D2 dopaminergic mechanisms.     

Potentiation by serotonergic inhibition of yawning induced by dopamine receptor agonists in rats

Low doses of the dopamine D2-receptor agonist, B-HT 920 (25 micrograms/kg, SC), and the dopamine D1/D2-receptor agonists, apomorphine (50 micrograms/kg, SC) and piribedil (1 mg/kg, SC), evoked yawning. However, the dopamine D1-receptor agonist, SK&F 38393 (2 mg/kg, SC), failed to induce yawning. The yawning responses induced by B-HT 920, apomorphine or piribedil were markedly increased without eliciting stereotypy by pretreatment with reserpine (5 mg/kg, IP, 24 hr). These yawning responses were also enhanced by p-chlorophenylalanine (PCPA) (300 mg/kg, IP, 72 hr), but not by alpha-methyl-p-tyrosine (300 mg/kg, IP, 6 hr). The yawning induced by B-HT 920 given alone and in combination with reserpine or PCPA was inhibited by spiperone (0.5 mg/kg, IP) or scopolamine (0.5 mg/kg, IP), but not by SCH 23390 (0.5 mg/kg, IP). The present results suggest that yawning is evoked by stimulation of dopamine D2-receptors having a high affinity and consequent muscarinic activation, and that the yawning induced by dopamine receptor agonists is potentiated by decreases in serotonergic neuron activity.