双氟哌酸在大鼠体内的药代动力学、组织分布与排泄

本文报告双氟哌酸(DFL)在大鼠体内的药代动力学、组织分布与排泄。DFL浓度用微生物法测定。根据F检验及AIC值判别房室模型。大鼠口服DFL后的药代动力学符合一模型,单剂口服100,200和500mg/kg DFL后Tmax分别为3.74,2.50和3.06小时,Cmax分别为14.28,19.72和35.85μg/ml,AUC分别为175,292.17和1041.23kg*h/ml,T1/2kc分别为5.11,8.35和17.88小时。大鼠口服     

131I-c(RGD)2的药代动力学及急性毒性研究

目的 用131I标记二硫键成环的RGD肽二聚体c(RGD)2,探讨其在裸鼠体内的药代动力学参数、急性毒性反应和死亡情况,评价其应用的安全性.方法 选取5只裸鼠为实验对象,每只经尾静脉注射131I-c(RGD)2(7.4 MBq/200μL),分别于注射后3、6、10、15、30、45、60、120、180及360min断尾取血5μL,测量血液的放射性计数,采用PKSolver软件进行药代动力学分析.另取裸鼠10只随机分为实验组及对照组,实验组每只经尾静脉注射131I-c(RGD)2(7.4 MB/60μL);对照组经尾静脉注射生理盐水60μL,观察注射后72 h内裸鼠的不良反应和死亡情况.结果 血液药-时曲线符合权重系数为1/CC的开放性二房室分布模型,其中分布相半衰期(t1/2α)为15.364 min,消除相半衰期(t1/2β)为123.125 min.注射131I-c(RGD)2后72 h内,裸鼠无不良反应与死亡.结论 c(RGD)2具有理想的药代动力学特点,且无明显毒性作用,这些均有利于其作为新药应用于临床.     

LC-MS/MS测定大鼠血浆中黄藤素含量及其药代动力学研究

目的建立大鼠血浆中黄藤素的LC-MS/MS定量方法,并利用此方法考察黄藤素在大鼠体内的药物动力学。方法色谱柱为ZorbaxEclipseXDB-C1(82.1mm×50mm,1.8μm),流动相为0.1%甲酸溶液-乙腈(70:30),采用多级反应模式(MRM)检测;通过大鼠眼底静脉取血,血浆经乙腈沉淀蛋白,取上清液进行LC-MS/MS分析,测定黄藤素血药浓度,通过DAS2.0计算其药动学参数。结果血浆中黄藤素在0.442~44.2ng/ml范围内呈现良好的线性关系,方法学精密度、回收率、稳定性等均符合要求;大鼠体内黄藤素药动学符合二室模型特征,灌胃给予40mg/kg黄藤素后,大鼠血浆中的黄藤素浓度在2.8h达峰值,t1/2为6h,最大血药浓度为19.8ng/ml。结论本研究建立的大鼠体内黄藤素测定方法灵敏度高、专一性好,可用于黄藤素的体内药物动力学研究,为黄藤素应用研究提供了有力支持。     

近红外实时在位检测系统及其在药代动力学中的应用研究

药代动力学研究中迫切需要一种实时在位检测方法。本文提出一种新的基于荧光光谱技术的实时在位检测方法,并搭建了一套用于大鼠体内药代动力学研究的监测系统,得到荧光强度和染料浓度的关系曲线,对大鼠体内荧光染料Cypate(近红外多次甲基菁染料)进行实时检测,并和体外荧光成像系统的结果比较来验证分析系统的可行性。结果表明:(1)Cypate浓度在0.098～25μg/ml范围内线性回归方程为y=73.249x+130.97(R2=0.999 1,P<0.001),高、中、低浓度的RSD分别为1.23%、6.29%和13.48%,检测灵敏度达到0.098μg/ml,特异性好;(2)Cypate的浓度变化与体外成像系统的结果基本一致(r=0.992 5),很好地反映了它在大鼠体内的代谢过程。论文的结论是为药代动力学研究提供了一种新的实时在位检测方法。     

双氟哌酸在犬体内的药代动力学及生物利用度研究

本文报告双氟哌酸(DFL)在犬体内的药代动力学及生物利用度研究。血药浓度用HPLC和微生物方法测定。犬口服和静脉注射DFL后的药代动力学分别符合一室和二室模型。犬口服40,20和10mg/kg DFL后平均5小时达到峰浓度,其峰浓度分别为7.91,4.01和1.79ug/ml,相应的消除半衰期为3.62,4.14和7.61小时,平均为4.94小时。犬静脉注射20mg/kg DFL后,即刻血药浓度为     

载紫杉醇聚己内酯-聚乙二醇-聚己内酯胶束的制备及药代动力学研究

目的制备新型可注射用载紫杉醇聚己内酯-聚乙二醇-聚己内酯(PCL-PEG-PCL)胶束,并评价和比较其与市售紫杉醇注射液在大鼠体内的药代动力学性质。方法以PCL-PEG-PCL为载体材料,通过薄膜-水化-超声法制备出载紫杉醇PCL-PEG-PCL胶束,并对其进行表征。以市售紫杉醇注射液为对照,采用SD大鼠尾静脉注射后观察载紫杉醇PCLPEG-PCL胶束的体内药代动力学,并用DAS 2.0药代动力学数据软件计算相关参数。结果载紫杉醇PCL-PEG-PCL胶束呈大小均匀的球形,具有明显的核壳结构;平均粒径为93 nm,多分散系数为0.19;载药量为28.98%,药物包封率为94.36%。体外释放研究表明,载紫杉醇PCL-PEG-PCL胶束具有缓释效果。药代动力学研究表明,两种制剂均符合二房室模型,市售紫杉醇注射液和紫杉醇聚合物胶束消除半衰期(t1/2β)分别为(1.96±0.27)h和(12.65±1.77)h,平均滞留时间(MRT)分别为(0.93±0.19)h和(11.18±1.41)h,体内总清除率(CL)分别为(0.44±0.05)L·kg/h和(0.10±0.01)L·kg/h,药-时曲线下面积(AUC0-∞)分别为(17.15±2.35)mg·h/L和(73.82±10.38)mg·h/L。结论成功制备了新型可注射用载紫杉醇PCL-PEG-PCL胶束,药代动力学研究表明,所研制的载紫杉醇PCL-PEG-PCL胶束明显延长紫杉醇在血液中的循环时间及消除半衰期,显著提高生物利用度,是一种有潜力的紫杉醇缓控释新剂型。     

载紫杉醇聚己内酯-聚乙二醇-聚己内酯胶束的制备及药代动力学研究简

目的制备新型可注射用载紫杉醇聚己内酯-聚乙二醇-聚己内酯（PCl-PEG-PCL）胶束,并评价和比较其与市售紫杉醇注射液在大鼠体内的药代动力学性质。方法以PCL-PEG-PCL为载体材料,通过薄膜-水化-超声法制备出载紫杉醇PCl-PEG-PCL胶束,并对其进行表征。以市售紫杉醇注射液为对照．采用SD大鼠尾静脉注射后观察载紫杉醇PCL-PEG-PCL胶束的体内药代动力学．并用DAS2．0药代动力学数据软件计算相关参数。结果载紫杉醇PCL-PEG-PCL胶束呈大小均匀的球形,具有明显的核壳结构;平均粒径为93nm,多分散系数为0．19;载药量为28．98％,药物包封率为94．36％。体外释放研究表明．载紫杉醇PCL-PEG-PCL胶束具有缓释效果。药代动力学研究表明．两种制剂均符合二房室模型．市售紫杉醇注射液和紫杉醇聚合物胶束消除半衰期（t1/2）分别为（1．96±0．27）h和（12．65±1．77）h,平均滞留时间（MRT）分别为（0．93±0．19）h和（11．18±1．41）h,体内总清除率（CL）分别为（0．44±0．05）L·kg／h和（0．10±0．01）L·kg／h,药-时曲线下面积（AUC0-∞）分别为（17．15±2．35）mg·h／L和（73．82±10．38）mg．h／L。结论成功制备了新型可注射用载紫杉醇PCL-PEG-PCL胶束．药代动力学研究表明．所研制的载紫杉醇PCL-PEG-PCL胶束明显延长紫杉醇在血液中的循环时间及消除半衰期．显著提高生物利用度,是一种有潜力的紫杉醇缓控释新剂型。     

氟喹诺酮类药物对肝微粒体酶系影响的研究

本实验首先以小鼠为研究对象,采用空白对照试验,比较分析了环丙沙星(Ciprofloxacin,CPFX)和司帕沙星(Sparfloxacin,SPFX)对安定镇静催眠的药理学效应的影响。并分析两药对安定在大鼠体内的药代动力学的影响,用CPFX和SPFX500mg/Kg·day剂量,每日给药一次,连续口服给药5天,用毛细管电泳法测定大鼠血药浓度,比较分析了给药前后安定血中消除半衰期(t1/2β),进一步是实验分析比较两药对大鼠肝微粒     

顺氯氨铂在肿瘤患者体内的药代动力学研究

本文报道顺氯氨铂在6例肿瘤患者体内的药代动力学参数及尿药排泄量。顺氯氨铂80mg/m~2静脉滴注,采用衍生化高效液相色谱法测定血药浓度和尿药浓度。结果表明顺氯氨铂在血浆中的衰减为二室开放模型,t 1/2α为0.51小时,t 1/2β为21.66小时。给药后7、24小时和5天内的尿药排泄量,分别为给药量的10～19％,11～20％,14～25％,反映有相当量的顺     

LHRH药代动力学试验

目的:研究黄体激素释放激素(Luteinizinghormone releasinghormone,LHRH)在大鼠体内的药动学规律。方法:用氯胺T法将125I标记到LHRH分子上(放化纯度96.2%),14只SD大鼠随机分为大剂量、小剂量组,每组7只,分别肌肉注射125I LHRH(小剂量组0.5mg.kg,大剂量组1.00mg.kg),给药后在21个不同时间点逐一取各鼠尾动脉血做放射性测定。结果:大鼠试验结果显示,大剂量组t1/2平均为67.83±20.84h;小剂量组半衰期平均为64.68±22.90h。LHRH的药—时曲线符合二室模型,大剂量LHRH和小剂量LHRH的主要药动学指标差别不大。结论:LHRH在大鼠体内的消除模式为二室模型,为一级动力学消除。     

PSD-007对宫颈癌Hela细胞光动力杀伤效应的剂量学研究

目的 探讨癌光啉（PSD-007）对人宫颈癌Hela细胞体外光动力杀伤效应及主要影响因素.方法 不同质量浓度（0、3.125、6.25、12.5、25、50、100 μg/ml）的PSD-007与Hela细胞共同孵育2h后,予以不同能量（0、0.6、1.2、2.4、4.8、9.6 J/cm2）635 nm波长的激光照射,以相同剂量光照和光敏剂剂量的人乳腺癌细胞系MCF-7光动力杀伤作用做对比,通过噻唑蓝（MTT）比色法测定细胞的光密度（OD）值及存活率;质量浓度为12.5 μg/ml的PSD-007与细胞共同孵育2h后,以不同能量（1.2、2.4、4.8 J/cm2）的激光照射,流式细胞术（FCM）分析细胞周期及凋亡率.结果 与空白对照组相比,单纯光敏剂PSD-007在＞25 μg/ml质量浓度下影响Hela细胞存活率,光动力疗法（PDT）对Hela细胞有更明显的杀伤效应,并且随着光敏剂质量浓度增加和光照能量密度增大,对细胞的杀伤效果逐渐增强.当光敏剂质量浓度＞12.5 μg/ml,光照能量＞4.8 J/cm2时,各组间细胞存活率的差异无统计学意义（P＞0.05）.FCM分析发现,PDT于G0/G1期阻断Hela细胞生长,凋亡诱导作用呈时间依赖性.结论 光敏剂PSD-007自身对体外人宫颈癌细胞系Hela细胞具有生长抑制作用,PSD-007介导的光动力杀伤效应更为显著,较人乳腺癌-7（MCF-7）细胞的PSD-007光动力作用有更低的使用剂量和光照剂量.     

Hypernickelemia following coronary arteriography, caused by nickel in the radiographic contrast medium

Meglumine diatrizoate ("Renografin-76", a radiographic contrast medium) contains sufficient nickel to cause hypernickelemia in patients after coronary arteriography. Nickel analyses by electrothermal atomic absorption spectrophotometry showed that nine lots of "Renografin-76" (760 g of meglumine diatrizoate per L) contained 144 +/- 44 micrograms Ni per L. Serum Ni concentrations became elevated in 11 patients after coronary arteriography (Ni dose = 19 +/- 4 micrograms per patient); peak Ni concentrations (increment = 1.8 +/- 0.4 micrograms Ni per L) occurred 0.25 or 0.5 h post-injection. Serum Ni concentrations diminished at 2 and 4 h post-injection and returned to base-line values at 24 h. The half-time (T1/2) for reduction of serum Ni concentrations averaged 1.5 h. Analysis of urine specimens from two patients showed that most of the Ni dose was excreted in urine within 24 hours. After iv administration of meglumine diatrizoate to rabbits (0.5 or 1.0 micrograms Ni per kg body wt), T1/2 values for elimination of Ni from the serum volume averaged 1.2 h, compared to T1/2 values of 5.7 and 7.4 h, respectively, when Ni was administered iv in NiCl2 or albumin solutions. Since "Renografin-76" contains edetate disodium (0.4 g per L), Ni is probably present as a Ni-EDTA complex, accounting for the rapid elimination of Ni following iv administration of the contrast medium to patients and rabbits. To reduce possible hazards of allergic or cardiovascular reactions to nickel, the authors recommend that Ni concentrations in radiographic contrast media should not exceed 10 micrograms per L.     

光动力疗法对人乳腺癌MCF-7细胞增殖凋亡的影响

目的 研究光动力疗法（PDT）对人乳腺癌MCF-7细胞增殖的影响和诱导凋亡的作用.方法 癌光啉（PSD-007）与细胞共同孵育2h后,以不同能量635 nm激光照射,通过噻唑蓝（MTT）比色法测定PDT后不同时间（0.5、1、3、6、12、24h）细胞的光密度（0D）值及存活率.DAPI染色观察PDT后不同时间细胞凋亡中细胞核形态学的改变.Annexin-V/PI双染法结合流式细胞术分析细胞凋亡率的变化.结果 PDT对MCF-7细胞的增殖有抑制作用,且随着PDT光照能量的提高而增强,PDT作用后细胞存活率随时间延长而逐渐降低.细胞形态学观察结果表明,MCF-7细胞呈典型的凋亡形态特征.Annexin-V/PI双染也证实PDT可以诱导细胞凋亡,且凋亡率随PDT作用后时间的延长而升高.结论 PDT能显著抑制MCF-7细胞增殖,诱导细胞凋亡,且其诱导肿瘤细胞的凋亡是一渐进性的过程,具有光照剂量和时间效应关系.     

侧脑室注射链脲佐菌素对大鼠海马突触相关蛋白PSD-95和Shank 1表达的影响

目的 观察侧脑室注射链脲佐菌素对大鼠脑PSD-95和Shank1表达的影响.方法 将大鼠随机分为正常对照组和模型组,模型组大鼠双侧侧脑室注射链脲佐菌素3mg/kg,第3d重复此剂量;对照组以人工脑脊液代替链脲佐菌素.21d后,取大鼠海马,用免疫组织化学和Western blotting方法观察突触相关蛋白PSD-95和Shank1的表达.结果 与对照组相比,模型组大鼠海马PSD-95和Shankl阳性细胞明显减少,PSD95和Shank1蛋白表达降低.结论 侧脑室注射链脲佐菌素使海马PSD-95和Shank1表达减少,干扰了神经元突触信号传导.     

Pharmacokinetics of amoxicillin-clavulanic acid combination after intravenous and intramuscular administration to turkeys and chickens

The pharmacokinetic behaviour of amoxicillin/clavulanic acid (4:1) combination was studied after intravenous and intramuscular administration of single doses (25 mg/kg body weight) to 15 turkeys and 15 chickens. The objective was to determine whether there are differences between turkeys and chickens in the disposition kinetics of amoxicillin and clavulanic acid. The plasma concentrations-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs after intravenous administration were best described by a two-compartment open model in turkeys and chickens. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. The body clearances of amoxicillin and clavulanic acid in turkeys were significantly slower than in chickens. The elimination half-life of amoxicillin was similar in turkeys (1.12 +/-0.09 h) and chickens (1.03 +/-0.11 h) after intravenous administration, but that of clavulanic acid differed significantly (P<0.05) between turkeys (1.12 +/-0.03 h) and chickens (0.98 +/- 0.05 h). After intramuscular administration both drugs had a significantly longer half-life (P<0.05) in turkeys and chickens than that after the intravenous treatment. The bioavailability after the intramuscular injection was high and similar with both drugs, but higher values were obtained for chickens than turkeys.     

Pharmacological modulation of the antigen-induced expression of the low-affinity IgE receptor (Fc epsilon RII/CD23) on rat alveolar macrophages.

Brown-Norway (BN) rats were sensitized by 3 aerosol exposures to ovalbumin (OA; 10 mg/ml) at days 1, 3 and 14. At day 21, the rats were challenged with the antigen or vehicle by aerosol. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the expression of Fc epsilon RII/CD23 was assessed by flow cytometry after staining with the BB10 monoclonal antibody. A maximum of 74% of the AM from sensitized and challenged BN rats expressed FC epsilon RII/CD23 24 h after OA exposure, compared to 12% of the cells from rats exposed to vehicle. Sprague-Dawley rats were passively sensitized by intravenous injection of 0.1 or 0.05 ml/kg mouse ascitic fluid containing dinitrophenyl (DNP)-specific monoclonal IgE (2682-1) and after 24 h exposed to an aerosol of 5 mg/ml of DNP-bovine serum albumin for 30 min. In this case also, antigen exposure induced the expression of Fc epsilon RII/CD23 on 75% AM, compared to 17% AM from saline-challenged rats. Such an induction of Fc epsilon RII/CD23 on AM was, however, not observed when the animals were challenged with either histamine, serotonin or acetylcholine by aerosol. The antigen-induced expression of Fc epsilon RII/CD23 on AM was inhibited upon treatment of the rats with ketotifen or beclomethasone. In addition, oral or aerosol administration of respectively BN 50730 or BN 52021 (two structurally unrelated platelet-activating factor antagonists), inhibited the antigen-induced Fc epsilon RII/CD23 expression on AM, indicating the participation of this lipid mediator in this process.     

Plasma tetrahydrobiopterin and its pharmacokinetic following oral administration

Tetrahydrobiopterin (BH(4)) is widely used as a therapeutic agent in patients with BH(4) deficiencies and mild forms of phenylketonuria (PKU) and there is an increasing need for the measurement of its plasma concentrations in patients with cardiovascular disorders. We measured BH(4) and total biopterin in dithioerythritol (DTE) pretreated plasma from four adults after oral administration of BH(4) (2, 10, and 20mg/kg body weight) using the differential iodine oxidation method. About 80% (range 64.8-92.2% ) of total biopterin was found as BH(4) when analyzed immediately after blood sampling. Compared with ascorbic acid as an antioxidant, DTE was more protective against oxidation of BH(4), particularly in samples stored over a period of 8 months. Without antioxidant (DTE or ascorbic acid) almost no BH(4) was detected. Furthermore, BH(4) and total biopterin were measured at different time intervals (up to 33 h after oral administration) and pharmacokinetic parameters T(max) (1-4h), C(max) (258.7-259.0 nmol/L biopterin at a dosage of 10mg/kg), and area under the curve (AUC=1708-1958 nmol(*)h/L up to T=10h) were estimated. The elimination half-life time was calculated to be 3.3-5.1h. Doubling the BH(4) dosage to 20mg/kg resulted in 60% higher AUC while sublingual BH(4) application (2mg/kg) resulted in 58-76% higher BH(4) plasma concentrations when compared with oral administration. These preliminary data suggest that in patients with BH(4) cofactor defects and BH(4)-responsive phenylalanine hydroxylase deficiency, BH(4) should be given in at least two to three daily doses and that sublingual administration may lower the required BH(4) dosage and subsequently the cost of treatment. Due to inter individual differences in pharmacokinetic properties, in some patients with hyperphenylalaninemia and mild PKU plasma BH(4) levels may be not high enough to fully activate the liver phenylalanine hydroxylase and thus lower blood phenylalanine levels. Assessment of plasma BH(4) or total biopterin concentrations may be a good way to control the efficacy of the loading test.     

Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals

OBJECTIVE: To compare the steady state plasma pharmacokinetics of 1000 mg of saquinavir (SQV) in a soft-gel capsule (SGC) formulation in combination with 100 mg of ritonavir (RTV) (capsules) in a twice-daily dosing regimen in HIV-1-infected individuals with historical controls who used 400 mg of SQV in a hard-gel capsule (HGC) formulation in combination with 400 mg of RTV and to investigate the plasma pharmacokinetics of the 1000 mg/100 mg regimen after normal and high-fat breakfasts. DESIGN: Open-label, crossover, steady-state pharmacokinetic study. METHODS: Six HIV-1-infected individuals who used either 1200 mg of SQV (SGC or HGC) three times daily or 400 mg twice daily in combination with 400 mg of RTV twice daily were included. Each patient was switched to 1000 mg of SQV SGC twice daily in combination with 100 mg of RTV twice daily. After 14 days, the patients came to the hospital for assessment of a pharmacokinetic profile during 12 hours. Patients were randomized to receive a high-fat (+/-45 g of fat) or normal (+/-20 g of fat) breakfast. After 7 days, a second pharmacokinetic profile was assessed after ingestion of the drugs with the alternate breakfast. A noncompartmental pharmacokinetic method was used to calculate the area under the plasma concentration versus time curve (AUC0-12h), the maximum plasma concentration (Cmax), the plasma trough concentration (C12h), and the elimination half-life in plasma (t1/2). The obtained pharmacokinetic parameters were compared with those of 12 patients using SQV HGC (400 mg twice daily) in combination with RTV (400 mg twice daily). RESULTS: The median values of the pharmacokinetic parameters for SQV SGC (1000 mg twice daily, normal breakfast) were: AUC0-12h, 18.84 h*mg/L; Cmax, 3.66 mg/L; C12h, 0.40 mg/L; and t1/2, 3.0 hours. The median values of the pharmacokinetic parameters for SQV HGC (400 mg twice daily, normal breakfast) were: AUC0-12h, 6.99 h*mg/L; Cmax, 1.28 mg/L; C12h, 0.23 mg/L; and t1/2, 3.9 hours. The exposure to SQV in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily was significantly higher than the exposure to SQV in a dosing regimen of 400 mg twice daily in combination with 400 mg of RTV twice daily. The pharmacokinetic parameters of SQV SGC in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily were not significantly different after ingestion of a high-fat or normal breakfast (p >.35). CONCLUSIONS: The combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily resulted in a higher exposure to SQV compared with the exposure to SQV obtained when SQV is used in the 400 mg/400 mg twice-daily combination with RTV. In this small number of patients, no significant differences in exposure were seen after ingestion of either a normal or high-fat breakfast. From a pharmacokinetic perspective, the combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily seems to be a good option for further clinical evaluation.     

海马CA1区5-HT_(1A)受体调控PTSD大鼠空间记忆的作用

目的:观察创伤后应激障碍(PTSD)大鼠海马长时程增强(LTP)的变化以及5-羟色胺1A受体(5-HT_(1A)受体)和突触后致密物蛋白95(PSD-95)的表达,探讨5-HT_(1A)受体调控PTSD大鼠空间记忆的机制。方法:健康成年SD大鼠36只,随机分为正常对照组和模型组,每组18只。模型组采用连续单一刺激构建PTSD大鼠模型。Morris水迷宫实验检测2组大鼠的学习和记忆能力,电生理实验检测强直性高频刺激对海马LTP的影响Western blot法和免疫荧光实验检测海马5-HT_(1A)受体和PSD-95蛋白的表达。结果:Morris水迷宫实验结果显示在各实验日模型组大鼠逃避平台的潜伏期较对照组显著延长(P0.05)。电生理实验结果显示在强直性高频刺激后,2组大鼠海马诱发电位的幅值明显升高,模型组诱发电位的幅值显著低于对照组(P0.01)。Westem blot实验和免疫荧光实验结果显示,与对照组比较,模型组大鼠海马CA1区5-HT_(1A)受体的表达显著增加(P0.05),但PSD-95的表达明显减少(P0.05)。结论:PTSD大鼠空间记忆能力减退,可能与海马CA1区5-HT_(1A)受体的表达增加和PSD-95的表达减少有关。     

Peri-sciatic administration of indomethacin early after nerve injury can attenuate the development of tactile allodynia in a rat model of L5 single spinal nerve injury

To clarify the role of cyclooxygenase in the peripheral nerve on the development of neuropathic pain, we investigated the effects of peri-sciatic administration of indomethacin on the development of allodynia in a model of L5 single spinal nerve injury. Peri-sciatic administration of indomethacin (1 mg/kg) was performed 3, 24, or 72 h after nerve injury (n=6/each). In rats with indomethacin 3 or 24 h after nerve injury, ipsi-lateral paw withdrawal thresholds 7-35 days after nerve injury were significantly higher compared with those in the control group (n=6: without peri-sciatic treatment) (P<0.05). However, such efficacy was no longer apparent when indomethacin was administered 72 h after nerve injury. These results suggest that peri-sciatic administration of indomethacin early (less than 24 h) after nerve injury can attenuate the development of allodynia.