枸杞籽油对慢性脑低灌注损伤大鼠的保护作用

目的 观察枸杞籽油对慢性脑低灌注损伤大鼠空间记忆及皮层自由基代谢的影响.方法 SD大鼠50只,随机分为假手术组、模型组及枸杞籽油高、中、低剂量组,除假手术组外,其余各组经双侧颈动脉结扎建立慢性脑低灌注损伤模型,枸杞籽油80、40、20 μL· kg-1灌胃60 d后,进行Morris水迷宫实验,检测其空间记忆能力,水迷宫实验结束后,取大鼠海马及皮层组织测其T-AOC活力及丙二醛(MDA)含量.结果 与假手术组相比,模型组出现明显的学习记忆障碍,治疗组较模型组学习记忆障碍有明显改善.与模型组相比,治疗组脑组织内T-AOC活性显著升高,MDA含量明显降低.结论 枸杞籽油能明显减轻大鼠慢性脑缺血所致认知功能障碍,可能与其清除自由基作用有关.     

半脑照射后大鼠的电刺激敏感性的研究

目的：探讨半脑照射后鼠的电刺激敏感性的特点及其变化规律。方法：采用4MeV电子束对8－10周龄的雌性SD大鼠作单次半脑照射，照射剂量分别为5，15，30Gy，另设对照组（只麻醉，不照射），于照射后第3，10，60天分别采用Y－迷宫测定大鼠的电刺激敏感性。结果：照射后第3天或第10天大鼠的电刺激敏感性受损最明显，60天有所恢复，30Gy组受损最明显，15Gy组次之，5Gy组最少。结论：半脑照射可使大鼠的电刺激敏感性下降，其下降程度与照射剂量和照射后观察时间有关。     

左乙拉西坦对癫痫大鼠认知功能的影响研究

目的:通过氯化锂-匹罗卡品(Li-pilo)诱导的癫痫大鼠模型,观察左乙拉西坦(LEV)对癫痫大鼠空间学习记忆能力及海马组织中突触素(SYN)表达的影响。方法:将96只SD大鼠随机分为NS组(生理盐水组),Li-pilo+LEV组(治疗组),Li-pilo组(模型组),LEV组(正常给药组),每组24只,于建模成功后7d,14d,28d通过RT-PCR方法观察各组大鼠海马组织中SYNmRNA的表达水平,并于第4周应用Morris水迷宫评价大鼠的学习记忆能力。结果:Morris水迷宫测试中Li-pilo+LEV组逃避潜伏期较Li-pilo组短(P<0.05);Li-pilo+LEV组穿越平台次数较Li-pilo组多(P<0.05)。PT-PCR测试各时间点NS组和Li-pilo+LEV组大鼠海马中SYNmRNA的表达量高于Li-pilo组(P<0.05)。结论:Li-pilo点燃的癫痫大鼠学习记忆能力减退,左乙拉西坦可改善癫痫大鼠的学习记忆能力,该作用可能与其调节海马组织中SYNmRNA的表达有关。     

大鼠全脑照射后早期1HMRS与病理变化

目的从病理学角度分析放射性脑损伤早期的质子磁共振波谱(^1HMRS)变化，为^1HMRS的临床应用提供理论依据。方法将成熟的SD大鼠25只随机分为对照组、10Gy、20Gy、30Gy单次照射组和30Gy分次(每周1次，每次10Gy)照射组，用6MeV电子线作垂直全脑照射，各组大鼠于照射后1个月均行MRI及^1HMRS检查，分析氮乙酰门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)等信号强度改变，以积分面积进行比较，计算NAA／Cr、Cho／Cr和NAA／Cho。各组大鼠在行^1HMRS检查后，立即断头处死取大脑后分两侧大脑半球，一侧大脑半球行常规病理HE染色检查，另一侧行电子显微镜检查。结果所有被检查大鼠的大脑MRI均未见异常表现；各照射组大鼠大脑的N从／Cr、Cho／Cr和NAA／Cho值与对照组相比均有统计学差异。结论用^1HMRS来监测大鼠全脑照射后脑组织内的NAA、Cho和Cr的浓度变化，在形态学发生改变之前就可检测出脑组织的代谢异常，并能反映大鼠全脑照射后早期脑组织内超微结构的改变。     

康寿灵对东莨菪碱痴呆模型大鼠学习记忆的保护作用

目的：观察康寿灵对东莨菪碱诱导的记忆障碍大鼠学习记忆的影响，并探讨其可能的作用机制。方法：各组大鼠分别用生理盐水（正常对照组、模型组）、康寿灵（低、中、高剂量组）和石杉碱甲（阳性对照组）灌胃37d。第31天起进行Morris水迷宫行为测试，连续7d。行为测试结束后，进行大鼠脑组织丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）及ATPase活性测定。结果：预先给予大鼠康寿灵30d可改善东莨菪碱导致的记忆障碍，使大鼠脑组织中抗氧化酶SOD、GSH-Px及ATPase活性升高，而MDA含量降低。结论：康寿灵对东莨菪碱引起的大鼠学习记忆能力障碍有明显保护作用，其作用机制可能与抗氧化作用密切相关。     

铜对大鼠学习记忆和海马区超微结构的影响

目的观察铜负荷饮食对大鼠空间学习记忆行为和海马超微结构的影响。方法 40只雄性大鼠随机分为模型组和空白对照组各20只,采用Morris水迷宫实验测试大鼠学习记忆能力,采用原子吸收法检测肝、脑组织铜元素含量,电镜技术观察海马区超微结构变化。结果 Morris水迷宫实验:模型组大鼠在定位航行试验中平均逃避潜伏期较正常对照组显著延长,空间探索试验中穿越平台次数较正常组明显减少(P<0.01),与正常对照组比较,模型组大鼠肝、脑组织铜含量明显增加(P<0.01),海马组织内模型组大鼠神经元突触间隙明显变宽(P<0.05),突触后致密物厚度明显变薄(P<0.05)。结论铜可能通过损伤海马超微结构引起大鼠学习记忆功能障碍。     

补肾健脾方对阿尔茨海默大鼠脑组织中cdk-5/p35表达的影响

目的 研究中药补肾健脾方对阿尔茨海默病(AD)大鼠脑组织标本中细胞周期蛋白依赖性蛋白激酶5(cdk-5)复合物(cdk-5/p35)表达的影响.方法 雄性SD大鼠随机分为5组:正常对照组,AD模型组,假手术组,AD大鼠补肾健脾方小剂量干预组及大剂量干预组,每组5只.采用鹅膏蕈氨酸毁损大鼠脑Meynert基底核制备AD动物模型,中药补肾健脾方分别以3.6 g·kg-1·d-1、7.2 g·kg-1·d-1灌胃.30 d后以水迷宫测试大鼠学习及记忆能力,以RT-PCR、Western blot方法分别检测脑组织中cdk-5/p35基因和蛋白的表达.结果 AD大鼠模型脑组织中cdk-5/p35基因和蛋白的表达显著高于正常对照组;大剂量及小剂量干预组大鼠脑组织中cdk-5/p35基因和蛋白的表达较AD模型组显著下降.结论 补肾健脾方可显著改善大鼠学习记忆功能,同时下调cdk-5/p35基因和蛋白的表达,提示cdk-5/p35可能参与了补肾健脾方治疗AD的作用机制.     

高胆固醇血症大鼠学习记忆及Aβ表达的时程变化

目的：观察高胆固醇血症大鼠学习记忆能力及脑内邱的时程改变，探讨高胆固醇血症与AD的相关性。方法：以高胆固醇饲料喂饲大鼠不同时间，观察其学习记忆能力、血清CHO、LDL-C水平及脑组织Aβ含量的变化。数据用均数士标准差（M±SD）表示，应用one-way ANOVA分析。结果：高胆固醇饲料喂饲8周后，可导致大鼠学习记忆障碍，表现在Morris水迷宫中，模型组的逃避潜伏期和游出距离较正常组明显延长，[第一段]     

高血氨对大鼠脑内NMDAR1 CREB表达的影响

目的探讨高血氨大鼠学习记忆能力改变的分子机制。方法雄性SD大鼠40只,随机分为2组,每组20只：正常对照组（A组）,高血氨模型组（B组）,Morris水迷宫观察动物学习记忆的变化,大鼠处死后,检测血氨,原位杂交检测N-甲基-D-天门冬氨酸受体1（NMDAR1）基因的表达,实时荧光定量聚合酶链反应（RTqPCR）检测大鼠脑组织环磷酸腺苷（cAMP）应答元件结合蛋白（CREB）基因的表达。结果与正常对照组比较,高血氨模型组大鼠血氨水平明显升高,其平均逃避潜伏期、游泳总距离均延长;并且大脑皮层、海马NMDAR1mRNA表达均下降,CREB基因表达亦均下降。结论高血氨模型大鼠学习记忆功能下降可能由于脑组织NMDAR1、CREB等基因表达下调所致。     

不同剂量美金刚对慢性脑缺血老龄大鼠认知障碍的改善作用及机制

目的：探讨美金刚（Memantine）对慢性脑缺血老龄大鼠认知障碍及海马区神经的保护作用及机制。方法：采用双侧颈总动脉结扎法（2VO）建立慢性脑缺血动物模型,将造模成功的31只12月龄雄性SD大鼠随机分为缺血组（n=7）和干预组（3.75,7.5,15,30 mg·kg^-1,n=6）,对照组（n=5）只分离血管不做结扎处理。采用水迷宫评估大鼠空间学习记忆功能,免疫荧光染色后对海马齿状回神经细胞增殖及CA1区凋亡细胞进行计数。结果：水迷宫实验显示：缺血组大鼠空间学习和记忆能力明显受损,与对照组和干预组相比有统计学差异（P<0.01）,美金刚干预后大鼠的空间学习和记忆能力得以改善（P<0.05）。免疫荧光染色显示：缺血组大鼠新生神经细胞计数明显多于对照组（P<0.01）,干预组齿状回新生神经细胞数量较对照组进一步增多（P<0.01）;缺血组大鼠凋亡细胞明显多于对照组（P<0.01）,美金刚干预后凋亡细胞数量较缺血组明显减少（P<0.05）。相关性分析表明,CA1区凋亡细胞数量与空间记忆功能呈负相关。结论：美金刚可通过促进海马神经细胞增殖、抑制细胞凋亡,改善认知功能障碍,且不同的药物剂量作用效果存在差异。     

1219例道路交通事故伤残案例分析

目的:探讨受伤者伤残等级、出生年度、伤残率的变化趋势。方法:对武汉市部分城区(市区)1993年和2003年发生并鉴定的1219份交通损伤案例的相关材料进行统计分析。结果:1993年各年龄组伤残等级调和均数值在5.6~9.1级之间,2003年在7.3~9.6级之间;伤残等级中Ⅰ-Ⅶ级构成比从22.40%下降到7.67%,Ⅷ-Ⅸ级无明显变化,Ⅹ级构成比从39.58%上升到57.67%;1993年各年龄组伤残率在69.18%~87.23%之间,2003年各年龄组伤残率在11.11%~73.17%之间;两年份伤残人数在各出生年度的分布无显著差异,两年份受伤总人数在各出生年度的分布7组中有6组无显著差异。结论交通损伤数增多,伤残程度减轻;伤残与年龄、出生年度有关。     

非痴呆性血管性认知功能障碍的中、西医研究现况

非痴呆性血管性认知功能障碍是血管性认知功能障碍的早期阶段,具有可逆性,故对该病的防治倍受关注。本文就目前中、西医对非痴呆性血管性认知功能障碍的认识及其治疗方法作一概述,以期为该病的临床治疗和科研活动提供一些新思路。     

Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses

The single dose and steady-state pharmacokinetics of buspirone and its metabolite 1-pyrimidinyl piperazine (1-PP) have been evaluated in normal volunteers and patients with renal or hepatic impairment, using a parallel group design, with assignment of patients to study group on the basis of the degree of renal (mild, moderate, severe) or hepatic (compensated or decompensated) impairment. Each healthy volunteer or patient received a single dose of 10 mg buspirone on Day 1 of the study, and starting 36 h after the first dose, healthy volunteers and patients received 10 mg doses of buspirone every 12 hours for 9 days. On the morning of Day 10 they received the last dose. Serial blood samples were collected on Days 1, 5 and 10 and plasma was analysed for buspirone and 1-PP. The plasma concentrations of buspirone and 1-PP were highly variable regardless of the renal or hepatic function. The peak concentrations (C_max) and area under the curves (AUC) of buspirone and 1-PP on Days D 5 and 10 were higher than on Day D 1. The trough levels (C_min) and AUCs (D 5 and 10) of buspirone and 1-PP indicated, that, regardless of renal or hepatic function, steady state was reached after 3 to 5 days of dosing. At steady-state, patients with renal or hepatic impairment had significantly higher C_max and AUC values of buspirone than in normal volunteers. However, the intensity and frequency of adverse experiences in patients with renal or hepatic impairment were not significantly different from those observed in normal volunteers. There was no correlation between the average plasma concentrations of buspirone ( ) and the degree of renal impairment judged by creatinine clearance. An excellent correlation was observed between of buspirone and serum albumin (r=0.862, and P<0.0001) as well as between and bromsulphalein clearance (r=0.678, P<0.0003).In view of high intra-and inter-subject variability in buspirone concentrations, definitive dosing recommendations for patients with compromised renal or hepatic function could not be made, but such patients should initially be dosed cautiously with buspirone.     

甲巯咪唑引起肝损害

患者女,42岁。因甲状腺功能亢进、结节性甲状腺肿,服用甲巯咪唑10mg,3次/d,利血生、普萘洛尔治疗1月。出现乏力、食欲不振、尿黄、皮肤重度黄疸,实验室检查显示:ALT1670U/L,AST1524.3U/L,TBil289.3μmol/L,DBil129.3μmol/L,ALB28.9g/L,A/G0.7,B超提示:肝回声偏粗。停用甲巯咪唑,其他药继续使用,并给予保肝治疗。1月后,患者症状逐渐好转,肝功能恢复正常。     

The pharmacokinetics of lamivudine in patients with impaired hepatic function

Objective: This study was designed to evaluate the effect of hepatic impairment on the pharmacokinetics of lamivudine. Methods: Sixteen patients not infected with hepatitis B virus or human immunodeficiency virus who had hepatic impairment due to liver cirrhosis were assigned to moderately or severely impaired groups by clinical signs/symptoms, ¹⁴C-aminopyrine metabolic activity and caffeine clearance and compared with eight healthy controls. Following a 300-mg dose of lamivudine, blood and urine samples were taken for drug assay. Results: Lamivudine was well tolerated in patients with hepatic impairment. There were no statistical differences in overall lamivudine exposure (in terms of AUC or C_max) or other major pharmacokinetic parameters i.e. CL_R, t_max and t_1/2, between healthy control subjects and patients with moderate or severe hepatic impairment. Conclusions: Hepatic impairment does not warrant dose modification of lamivudine based on this single-dose pharmacokinetic study. Received: 5 September 1997 / Accepted in revised form: 7 February 1998     

Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function

Objective: The influence of liver disease on the pharmacokinetics of candesartan, a long-acting selective AT₁ subtype angiotensin II receptor antagonist was studied. Methods: Twelve healthy subjects and 12 patients with mild to moderate liver impairment received a single oral dose of 12 mg of candesartan cilexetil on day 1 and once-daily doses of 12 mg on days 3–7. The drug was taken before breakfast. Serial blood samples were collected for 48 h after the first and last administration on days 1 and 7. Serum was analyzed for unchanged candesartan by HPLC with UV detection. Results: The pharmacokinetic parameters on days 1 and 7 revealed no statistically significant influence of liver impairment on the pharmacokinetics of candesartan. Following single dose administration on day 1, the␣mean␣C_max was 95.2 ng · ml⁻¹ in healthy subjects and 109 ng · ml⁻¹ in the patients. The AUC_0−∞ was␣909 ng.h · ml⁻¹ in healthy volunteers and 1107 ng.h · ml⁻¹ in patients and the elimination half-life was 9.3 h in healthy volunteers and 12 h in the patients. At steady state on day 7, mean C_max values were similar in both groups (112 vs 116 ng · ml⁻¹); the AUC_τ was 880 ng.h · ml⁻¹ in healthy subjects and 1080 ng.h · ml⁻¹ in patients while the elimination half-life was 10 h in healthy subjects and 12 h in the patients with liver impairment. The AUC_0−∞ on day 1 was almost identical to the AUC_τ on day 7. A moderate drug accumulation of 20%, which does not require a dose adjustment, was observed following once-daily dosing in both groups. No serious or severe adverse events were reported. Conclusion: Mild to moderate liver impairment has no clinically relevant effect on candesartan pharmacokinetics, and no dose adjustment is required for such patients. Received: 24 November 1997 / Accepted in revised form: 18 February 1998     

甲苯咪唑引起肝损害

1例30岁女性患肝包虫病,术后给予口服甲苯咪唑200mg,2次/d。10d后,患者ALT升高到101U/L,将甲苯咪唑减量至100mg,2次/d。服药20d后,ALT升为200U/L,给予保肝治疗,患者肝功能降至正常范围。继续服用甲苯咪唑,患者ALT升至300U/L,再次停服甲苯咪唑。半月后患者ALT为605U/L,TBil为126μmol/L,并出现纳差、尿黄等症状。给予保肝和对症治疗,25d后患者症状好转,肝功能恢复正常。     

Minimal impact of hepatic and renal impairment on plasma protein binding of lenvatinib,and identification of its major plasma binding protein

Plasma protein binding (PPB) can be different depending on the status of hepatic or renal functions. In this study, the PPB of lenvatinib was determined using equilibrium dialysis in plasma from healthy volunteers and from subjects with mild, moderate, or severe hepatic impairment or renal impairment. Plasma from these subjects, fortified with lenvatinib at four concentrations (20, 200, 500, or 1200 ng/ml), was dialysed against phosphate buffered saline (PBS), and then determinations of the total concentrations of lenvatinib in plasma and unbound concentrations in PBS were made. In addition, the binding of lenvatinib was determined in human serum albumin (HSA), α₁‐acid glycoprotein (AAG), and human γ‐globulin (HG) in order to identify major binding proteins in human plasma. The PPB of lenvatinib in subjects with HI or RI ranged from 97.5% to 98.2% in hepatic impairment and 98.0% to 98.4% in renal impairment, which was similar to that of healthy volunteers. The binding of lenvatinib to HSA, AAG, and HG was 96.6%–97.1%, 46.4%–69.9%, and 19.1%–23.9%, respectively. These findings suggest that lenvatinib mainly binds to HSA and neither renal nor hepatic impairment impacts the PPB of lenvatinib.     

致他汀类药物停药相关的不良反应的处置

他汀类药物是目前防治包括冠心病在内的动脉粥样硬化性疾病的主要药物,但临床应用仍不尽人意。他汀使用率和达标率低的原因之一是部分患者不能耐受他汀类药物治疗。与停用他汀相关的主要不良反应是肌肉损害和肝脏损害。本文介绍了如何预防和处置他汀类药物导致的肝损害和肌肉损害等不良反应,并提出他汀和其他药物相互作用导致的不良反应应引起关注。