天麻茎秆水提物的抗惊厥作用

【目的】研究天麻茎秆(Gastrodia elata stalk)水提物的抗惊厥作用及其可能的作用机制。【方法】以SPF级ICR小鼠为研究对象，采用戊四氮(PTZ)和N-甲基-D -冬氨酸(NMDA)构建2种小鼠癫痫模型，以卡马西平(80 mg/kg)为阳性对照，以相同体积的蒸馏水为空白对照，通过检测小鼠脑中γ-氨基丁酸(GABA)、谷氨酸(Glu)、一氧化氮(NO)、五羟色胺(5-HT)、Na⁺-K⁺-ATP酶(Na⁺-K⁺-ATP)、天冬氨酸(Asp)、总抗氧化能力(AOC)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GSR)、丙二醛 (MDA)、白细胞介素1β(IL-1β)、白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)水平的变化，分析天麻茎秆水提物高、中、低(2 000，1 000，500 mg/kg) 3个剂量对模型小鼠惊厥发作的行为学影响，观察各组小鼠脑皮层及海马组织的病理学变化，免疫组织化学方法测定脑皮层、海马组织中c-Fos、TLR4蛋白的表达水平。【结果】与空白对照组相比，2种模型组小鼠发生惊厥数及死亡率极高，其脑组织中GABA、5-HT、Na⁺-K⁺-ATP、AOC、CAT、GSH、SOD、GSR、IL-10的含量降低，Glu、Asp、NO、MDA、IL-1β、TNF-α的含量升高，脑皮层和海马组织中c-Fos、TLR4蛋白表达水平升高，海马神经元受损。天麻茎秆高、中、低剂量组和卡马西平组均可改善由PTZ、NMDA所致上述指标的变化，延长小鼠的惊厥潜伏期，缩短惊厥持续时间，减少惊厥次数，降低惊厥强度及死亡率。【结论】天麻茎秆具有良好的抗惊厥作用，能缓解由PTZ和NMDA诱发的小鼠惊厥。     

Effect of phenobarbitone on the low-dose dexamethasone suppression test and the urinary corticoid: creatinine ratio in dogs

OBJECTIVES: To investigate potential effects of phenobarbitone on the low-dose dexamethasone suppression (LDDS) test and urinary corticoid to creatinine ratio in dogs in a controlled prospective study and in a clinical setting. ANIMALS: Ten crossbreed experimental dogs and 10 client-owned dogs of mixed breeds treated chronically with phenobarbitone to control seizures. PROCEDURES: Experimental dogs were allocated to treatment (6 mg/kg oral phenobarbitone, n = 6) and control (n = 4) groups. LDDS tests (dexamethasone 0.01 mg/kg intravenously, cortisol concentration determined at 0, 2, 4, 6 and 8 h) were conducted repeatedly over a 3-month period. Urinary corticoid to creatinine ratios were measured before LDDS tests. A single LDDS test was performed on 10 epileptic dogs. RESULTS: LDDS and urinary corticoid to creatinine ratios in dogs were not affected by treatment with phenobarbitone. CONCLUSIONS: Phenobarbitone does not interfere with LDDS testing regardless of dosage or treatment time. Urinary corticoid to creatinine ratios are also unaffected.     

杜仲雄花乙酸乙酯提取物的抗惊厥作用研究

研究杜仲雄花乙酸乙酯提取物的抗惊厥作用。观察不同剂量乙酸乙酯提取物对小鼠自主活动的影响、直接中枢镇静作用和抗惊厥作用。杜仲雄花乙酸乙酯提取物具有显著的中枢镇静作用,显著减少小鼠的自主活动次数;显著减少惊厥小鼠数,延长惊厥潜伏期。杜仲雄花乙酸乙酯提取物具有良好的抗惊厥作用。     

Pharmacokinetics of single-dose oral pregabalin administration in normal dogs

ObjectiveTo describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.Study designProspective experiment.AnimalsSix adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.MethodsAfter jugular vein catheterization, the dogs received a single oral dose of pregabalin (～4 mg kg^?1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.ResultsNo adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL^?1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL^?1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (C_max) = 7.15 (4.6–7.9) μg mL^?1; time for C_max to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL^?1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL^?1.Conclusions and clinical relevancePregabalin 4 mg kg^?1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.     

天麻种子的抗惊厥作用研究

【目的】研究天麻种子的抗惊厥表现及可能的作用机制。【方法】以SPF级ICR小鼠为研究对象,用戊四氮(PTZ)构建小鼠惊厥模型,以80 mg/kg卡马西平为阳性对照,体积分数0.5%羧甲基纤维素钠溶液为空白对照,通过检测小鼠脑中γ-氨基丁酸(GABA)、谷氨酸(Glu)、一氧化氮(NO)、Na~+-K~+-ATP酶(Na~+-K~+-ATP)、天冬氨酸(Asp)、五羟色胺(5-HT)含量的变化,分析天麻种子高、中、低(900,450,225 mg/kg)3个剂量对模型小鼠惊厥发作行为的影响,观察不同处理组小鼠脑皮层及海马组织的病理学表现,免疫组织化学方法测定组织中c-fos蛋白和TLR4蛋白的表达水平。【结果】与空白对照组相比,PTZ模型组发生惊厥的小鼠及死亡率高达100%,其脑组织中GABA、5-HT、Na~+-K~+-ATP含量降低,Glu、Asp、NO含量升高,脑皮层及海马组织中的c-fos、TLR4蛋白表达水平升高,海马神经元受损。天麻种子高、中、低3个剂量组和卡马西平组均可改善PTZ所致的上述指标变化,可延长惊厥小鼠的潜伏期,缩短惊厥持续时间,减少惊厥次数,降低惊厥强度及死亡率。3个天麻种子组中尤以高剂量组效果最为明显。【结论】天麻种子具有良好的抗惊厥作用,能对抗由PTZ诱发的小鼠惊厥,其作用机制与卡马西平相似。