奥硝唑对映体对小鼠中枢抑制作用的机制探究

目的:探讨右奥硝唑中枢抑制效应与脑内γ-氨基丁酸(gamma amino butyric acid,GABA)系统的关系。方法:经不同剂量右/左奥硝唑处理后使用N,N-二甲基二吖啶硝酸盐(1-(Ethoxycarbonylmethyl)-6-methoxyquinolinium bromide,MQAE)荧光探针检测原代培养小鼠皮层神经元氯离子浓度,并通过western blot方法检测GABAA受体亚基的表达。尾静脉注射给予右/左奥硝唑后测定小鼠高架十字迷宫行为。结果:右奥硝唑剂量依赖性激活小鼠皮层神经元的氯离子通道,经右奥硝唑处理后的皮层神经元能增加GABAA受体α1亚基的水平,且右奥硝唑有潜在的抗焦虑活性。结论:右/左奥硝唑中枢作用不同,右奥硝唑较强的中枢抑制作用可能与激活GABA系统有关。     

高效液相色谱法拆分奥硝唑对映体

目的：建立奥硝唑对映体的手性拆分方法,并用于测定左旋奥硝唑原料和制剂中的右旋异构体。方法：采用高效液相色谱法,Ultron ES OVM手性柱(150mm×4.6mm,5μm,Agilent),通过考察影响分离的一些因素,最终确定拆分的最佳条件,即以20mmol[DK]?L-1醋酸钠(pH 5.4)-乙腈（98[DK]∶2）为流动相,流速为0.6mL[DK]?min-1,检测波长为320nm。结果：在此条件下,奥硝唑对映体之间的分离度为2.5,奥硝唑对映体最小检出浓度为0.1μg[DK]?mL-1。结论：所建立的方法简便、快速,可用于分离和测定左旋奥硝唑原料和制剂中的右旋异构体。     

注射用左旋奥硝唑磷酸酯二钠对小鼠神经系统的影响

目的 探讨注射用左旋奥硝唑磷酸酯二钠静脉注射对ICR小鼠神经系统的影响.方法 将小鼠分为空白组、左旋奥硝唑(S-O)组、右旋奥硝唑磷酸酯二钠(R-ODP)组和左旋奥硝唑磷酸酯二钠(S-ODP)低、中、高剂量组(50、100、200 mg·kg-1);观察药物延长戊巴比妥钠致小鼠睡眠的时间、对运动及平衡能力的影响和对自发活动的影响.结果 S-ODP、S-O、R-ODP均可明显缩短小鼠的入睡潜伏期,延长睡眠时间;对小鼠的自发活动次数有一定的抑制作用;可降低小鼠转棒掉落时的转速、缩短掉落时间及经过路程.相同剂量R-ODP的以上作用明显强于S-ODP.结论 较高浓度S-ODP与巴比妥类镇静催眠药物有明显的协同作用,对小鼠自发活动及运动平衡能力也有轻微的影响,但效果弱于相同剂量的R-ODP.     

外翻肠囊法研究奥硝唑对映体在大鼠不同肠段的吸收特性

目的考察奥硝唑在大鼠各肠段的吸收特性及奥硝唑两手性对映体在大鼠不同肠段吸收的差异性。方法采用大鼠外翻肠囊法,以HPLC手性色谱柱法测定奥硝唑在不同肠段的吸收量以及S-奥硝唑及R-奥硝唑的同一肠段肠吸收量,并分别计算吸收速率常数(Ka)和表观渗透系数(P_(app)),同法考察了P-蛋白抑制剂(维拉帕米和环孢素A)对奥硝唑肠吸收特性的影响。结果奥硝唑在不同肠段吸收均呈线性,符合零级药物吸收速率,吸收趋势为空肠>回肠>结肠。在空肠段两对映体以近于1∶1的比例同时吸收,吸收速率不存在显著差异,随着供试液中奥硝唑质量浓度的上升,Ka呈线性增加(R~2>0.99),Paap基本保持不变,P-蛋白抑制剂对奥硝唑的肠吸收没有显著性影响(P>0.05)。结论奥硝唑在不同肠段的吸收有差异,空肠部位是吸收的最佳部位(P<0.05),S-奥硝唑与R-奥硝唑在肠道中吸收速率不存在显著差异,吸收以被动扩散机制为主,奥硝唑不是P-糖蛋白的底物。     

奥硝唑合剂对牙体牙髓病的治疗效果观察

目的观察并分析对牙体牙髓患者者使用奥硝唑合剂进行治疗的临床效果。方法在本院2014年6月至2016年9月接诊的牙体牙髓患者者中随机选取符合此次研究纳入标准的72例患者作为研究对象,并对如上患者实施分组治疗,对照组患者均采取常规根管治疗,观察组则使用奥硝唑合剂治疗,各36例。结果观察组临床治疗总有效率约为97.2%,较之对照提高程度明显(P<0.05)。对比两组不良反应发生概率,观察组也有显著降低(P<0.05)。结论对牙体牙髓患者者使用奥硝唑合剂进行临床治疗可在极大程度上提高该病症的临床治疗效果,并可有效降低不良反应的发生概率,提高临床治疗的安全性,故值得临床加以推广应用。     

派丽奥软膏联合奥硝唑合剂治疗对牙髓体病变临床疗效和牙周指数的影响

目的:分析在牙髓体病变中派丽奥软膏联合奥硝唑合剂治疗的临床疗效和对牙周指数的影响。方法:选择我院2018年1月—2019年5月收治的64例牙髓体病变患者,随机分为对照组和研究组,每组32例。对照组给予奥硝唑合剂治疗,研究组给予派丽奥软膏联合奥硝唑合剂治疗,对比两组治疗效果、牙周指数及不良反应。结果:研究组治疗有效率(96.88%,31/32)高于对照组(81.25%,6/32)(P<0.05),BI、PLI、GI、PD水平低于对照组(P<0.05)。两组不良反应发生率无明显差异(P>0.05)。结论:在牙髓体病变治疗中,派丽奥软膏联合奥硝唑合剂可实现较高的治疗有效率,还能显著改善牙周指数,治疗效果显著。     

氨甲喋呤对映体对ECV304细胞抑制作用及其机制

目的探讨氨甲喋呤[(±)MTX]及其对映体[(+)MTX、(-)MTX]对ECV304细胞的生长抑制作用并探讨其机制。方法采用培养的ECV304细胞,应用MTT比色法分析其活性;用光学显微镜观察细胞的形态学变化;碘化丙啶(PI)单染流式细胞术检测细胞周期。结果在0.1～150μmol·L-1范围内,(+)MTX、(-)MTX和(±)MTX作用于ECV304细胞24、48、72h,均抑制细胞ECV304增殖,但抑制强度依次为(+)MTX>(±)MTX>(-)MTX,倒置显微镜观察不同浓度(±)MTX、(+)MTX和(-)MTX作用ECV304细胞不同时间后,出现细胞体积变小、核固缩等形态学改变。用10μmol·L-1的(+)MTX、(-)MTX和(±)MTX作用ECV304细胞48h后,PI单染流式细胞术检测ECV304细胞周期的影响,表明MTX消旋体及单一体干扰ECV304细胞DNA合成。结论(+)MTX和(-)MTX对ECV304细胞的抗增殖作用具有化学结构的立体选择性,(+)MTX的抗ECV304细胞增殖作用明显强于(-)MTX。     

银杏叶提取物对糖尿病肾病模型小鼠肾脏炎症的抑制作用及机制

目的 探讨银杏叶提取物（GBE）抑制糖尿病肾病（DN）模型小鼠肾脏炎症的作用及其可能机制。方法 以高脂高糖喂养KK/Ay小鼠建立DN模型,并分为模型组、阳性对照组[二甲双胍200 mg/（kg·d）]和GBE低、高剂量组[100、200 mg/（kg·d）],每组6只;另取普通饲料喂养的C57BL/6J小鼠6只,作为对照组。各药物组小鼠灌胃相应药液,对照组和模型组小鼠灌胃等体积生理盐水,每天1次,连续8周。检测小鼠的体重、空腹血糖、24 h摄食量、24 h尿量和血清单核细胞趋化蛋白1(MCP-1)、白细胞介素12(IL-12)、IL-10、晚期糖基化终末产物（AGEs）、血尿素氮（BUN）、血肌酐（Scr）水平,计算其双侧肾脏质量与体重的比值,观察其肾皮质的病理损伤和纤维化改变,并检测其肾皮质中巨噬细胞极化标志蛋白[M1型：诱导型一氧化氮合酶（iNOS）;M2型：精氨酸酶1(Arg-1)]和AGEs-晚期糖基化终末产物受体（RAGE）/Ras同源基因家族成员A(RhoA/)/Rho相关螺旋卷曲蛋白激酶（ROCK）信号通路相关蛋白的表达情况。结果 与模型组比较,GBE低、高剂量组小鼠肾皮...     

盐酸右美托咪定对脑缺血再灌注损伤小鼠的保护机制

目的 研究盐酸右美托咪定(Dex)对脑缺血/再灌注实验动物氧化应激水平的影响及初步机制.方法 将108只C57小鼠随机分为假手术组、模型组和实验组,每组36只.实验组于再灌注前30 min,腹腔注射盐酸右美托咪定25μg·kg-1,假手术组和模型组同时间点给予等量生理盐水.用2,3,5-三苯基氯化四氮唑法(TTC)观察...     

右美托咪定对脓毒症小鼠炎症反应的影响及机制研究

目的:研究右美托咪定(Dex)对脓毒症小鼠炎症反应的影响及机制。方法:将小鼠随机分为正常对照组、模型组、微小RNA-146a(mi R-146a)抑制剂(50 mg/kg)+Dex(50μg/kg)组和Dex低、中、高剂量组(10、30、50μg/kg),每组10只。除正常对照组外,其余各组小鼠ip脂多糖建立脓毒症模型,0.5 h后ip相应药物。药物干预6 h后,实时荧光定量聚合酶链式反应法检测各组小鼠外周血单核细胞中mi R-146a表达及其靶基因白细胞介素1(IL-1)受体相关激酶(IRAK1)、肿瘤坏死因子(TNF)受体相关因子6(TRAF6)m RNA表达,Western blot法检测外周血单核细胞中IRAK1、TRAF6蛋白的表达,酶联免疫吸附法检测血清中TNF-α、IL-6的水平。结果:与正常对照组比较,模型组小鼠的mi R-146a表达增强,TNF-α、IL-6水平升高,IRAK1、TRAF6 m RNA和蛋白表达增强(P<0.01)。与模型组比较,Dex中、高剂量组小鼠外周血单核细胞中mi R-146a表达增强,TNF-α、IL-6水平下降,IRAK1、TRAF6蛋白表达减弱(P<0.05或P<0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P>0.05)。与Dex高剂量组比较,mi R-146a抑制剂+Dex组小鼠外周血单核细胞中mi R-146a表达减弱,TNF-α、IL-6水平升高,IRAK1、TRAF6蛋白表达增强(P<0.05或P<0.01),但IRAK1、TRAF6 m RNA表达变化不明显(P>0.05)。结论:Dex可抑制脓毒症小鼠炎症反应,其机制可能与诱导mi R-146a表达、抑制Toll样受体4/核因子κB通路中的两个重要接头蛋白IRAKI和TRAF6的表达有关。     

左旋和右旋奥硝唑对犬神经毒性的比较研究

目的 本实验进行了Beagle犬静脉输注奥硝唑及其光学对映体神经毒性的比较研究.方法 Beagle犬连续静脉给药2周,观察动物的一般状况和体重变化.给药结束时进行大体解剖,血液学和血液生化学,器官重量和组织病理学检查.结果 左旋奥硝唑组(200mg/kg,iv)Beagle犬仅在给药后1～3h内出现流涎、呕吐、不自主排便、排尿等症状;动物体重增长受到轻度抑制,进食量轻微减少,但与溶媒对照组无明显差异.右旋奥硝唑组(200mg/kg,iv)动物出现流涎、呕吐、四肢无力、不能站立,抽搐等毒性反应,随给药次数增加,毒性反应表现更加明显,且恢复时间延长,对动物体重及进食量有明显抑制.消旋奥硝唑组的毒性反应介于两者之间.各组的血液学和血液生化学检查结果以及器官重量无明显差异.组织学检查结果显示右旋体组犬小脑的蒲肯野细胞数目较溶媒对照组和左旋体组明显减少,细胞呈轻度变性.结论 在本试验条件下,左旋体组Beagle犬给药后的毒性反应比右旋体组轻.右旋体组犬小脑出现可见的蒲肯野细胞变性.结果提示,奥硝唑左旋体较右旋体毒性小,临床用药应更加安全.     

弓形虫RH强毒株对大白鼠中枢神经系统影响的研究

目的 探讨弓形虫感染对中枢神经系统的影响.方法 对不同孕期的大鼠腹腔感染弓形虫,观察其产仔及仔鼠生长存活情况,用迷宫实验检测仔鼠学习分辨及记忆能力,并对死亡的仔鼠大脑进行病理切片. 结果 早期感染弓形虫者其仔鼠在迷宫测试中,学习分辨能力及记忆能力显著低于对照组(P＜0.001);不同孕期感染各组学习成绩超过对照组算术均数3.21天的仔鼠数中,早期感染组所产仔鼠与对照组差异有显著性(P＜0.05);早期、中期感染组所产仔鼠在学习中的电击次数超过对照组算术均数4.41次的仔鼠数与对照组差异呈显著性(P＜0.05);晚期感染组其仔鼠6～7周死亡数显著高于对照组(P＜0.01)且大脑病理切片结果显示:大脑皮质空洞,大量嗜酸性细胞增生、集聚,提示寄生虫感染.结论 不同孕期感染弓形虫均可导致胎儿的先天性感染,造成中枢神经系统的损害.     

Pharmacological evaluation of Potentilla alba L. in mice: adaptogenic and central nervous system effects

Context: Potentilla alba L. (Rosaceae) rhizomes have anti-inflammatory, antioxidant, and adaptogenic effects and are used for the treatment of diarrhea and intestinal colic. However, the data concerning the adaptogenic and central nervous system activities of P. alba are fragmentary.

Objectives: To determine the effect of oral administration of dried P. alba extract on the swimming endurance, light/dark exploration, and open-field tests for mice.

Materials and methods: The mice were orally administered Rhodiola rosea extract (RR group); dry extract of P. alba at doses of 12, 36, or 72?mg/kg (groups: PA12, PA36, and PA72); or distilled water (control group) for 7 consecutive days.

Results: The swimming times of the RR, PA36, and PA72 groups were significantly longer than those of the control group. The administration of P. alba significantly increased the light time, latency time, and the number of rearings in a dose-dependent manner. In the open-field test, the P. alba extract at a dose of 12?mg/kg produced a significant increase in the frequency of head dipping and the number of squares crossed and a significant decrease in grooming compared with the control treatment.

Conclusion: The current findings demonstrate that P. alba extracts significantly increased swimming endurance time and have anxiolytic-like action with a predominant locomotor component.     

Pharmacological effects of oxaprotiline enantiomers on the central serotonin system

The study examined the effect of both oxaprotiline (OXA) enantiomers on the serotonin system in rats and mice. (+)-OXA and (-)-OXA partly inhibit the behavioral syndrome induced by 8-OH-DPAT and 5-methoxy-dimethyltryptamine (5-MeODMT) in normal and reserpinized rats. Imipramine and desipramine produced a similar but less potent effect. (+)-OXA and, to a lesser extent, (-)-OXA antagonized the m-chlorophenylpiperazine (m-CPP)-induced hypothermia in mice. Imipramine and desipramine produced no such effect. (+)-OXA attenuated the head-twitch response to L-5-HTP in mice, but (-)-OXA has no such action. Neither enantiomer inhibited the fenfluramine-induced hyperthermia in rats nor antagonized m-CPP-induced stimulation of hind limb flexor reflex of spinal rat. The obtained results indicate that both enantiomers may have a 5-HT1B-antagonistic action and a less potent 5-HT1A-antagonistic one; on the other hand, they shown no 5-HT2-antagonistic activity.     

Maximal inhibition of cholinesterase in the central nervous system

In experiments on mice treated with pralidoxime iodide (pyridine-2-aldoxime methiodide; PAM) and atropine, the cholinesterase activity in the brain was assayed after poisoning with very high doses of organophosphorous anticholinesterases. Acetylcholine was added to the buffer solution in which the brains were homogenized. This precaution reduced the combination between free inhibitor present in the tissue and active enzyme, and the cholinesterase activity found was below 0·5% of controls. When the experimental data were corrected for spontaneous reactivation in vitro during incubation, the calculated activities in vivo were even less. It is concluded that mice can survive complete inactivation of the cholinesterase in the central nervous system, if enough atropine is given to protect the animals against the toxic effects of the accumulating acetylcholine.     

Pharmalogic effects of benzonitrile on the central nervous system

The present experiments intended to explore the psychopharmacological properties of benzonitrile on mice. Benzonitrile decreased motility, muscular force and inquisitiveness. The hypnotic effects of chloral and pentobarbital were increased by benzonitrile. The drug antagonized reserpine-induced palpebral ptosis and apomorphine-induced stereotypy. That benzonitrile was more effective against convulsions induced by pentetrazol and electric shock than those induced by strychnine suggested a central site of action. Perhaps benzonitrile interfers with the release or the action of central amines.     

Species-dependent effects of fenfluramine on the central nervous system

The cortical effects of fenfluramine and a metabolite, norfenfluramine, were studied in rabbits and cats. The parent compound produced slow waves in the e.e.g. which were compatible with sedation in cats. Norfenfluramine also produced slow waves and apparent sedation in cats, but neither compound produced marked changes in the cortical waves of rabbits. When cortical waves in both species were slowed with pentobarbitone, fenfluramine increased the frequency of the waves in rabbits but did not alter the frequency in cats. Both fenfluramine and the metabolite blocked cortical after-discharges in both species. There is no apparent explanation for the differences in the action of the two drugs in the two species.     

Pharmacologic effects of glycerolformal on the central nervous system

Glycerolformal is not devoid of action on mice psychomotor behaviour. Administered through the digestive tract with infralethal doses, it can exercice depressing effects on muscular strength and sensitivity to pain without affecting inquisitiveness. It opposes the stimulating effects specific to pentetrazol, amphetamine and apomorphine and is a protection against electric convulsions but tends to increase the toxicity of tryptamine.