曲马多对小鼠镇痛作用的药物代谢动力学研究

目的　探讨曲马多在小鼠体内的药物代谢动力学。方法　采用药效—药代统一模型 ,以小鼠腹腔注射醋酸后扭体反应次数为镇痛效应指标 ,测定时—效、量—效关系 ,进一步求时间—体存生物相当药量曲线及相应药代动力学参数。结果　曲马多在小鼠的镇痛作用呈显著的时—效、量—效关系 ,其镇痛作用效量半衰期(T1 /2 ,ED)为 4 68min ,消除速率常数K为 0 1 4 8。结论　曲马多母核药物与多种代谢产物均有镇痛作用 ,此法比单纯测定曲马多的血药浓度更能科学地反映药物在作用部位的药效变化规律     

Walker256乳腺癌细胞构建大鼠胫骨骨癌痛模型

目的：探讨以Walker256大鼠乳腺癌腹水瘤细胞制备大鼠胫骨骨癌痛模型，为骨癌痛机制和治疗研究提供有用的工具。方法：以Walker256乳腺癌细胞接种幼年雌性SD鼠腹腔制备腹水瘤细胞，将15μl腹水瘤细胞注入雌性成年SD鼠左侧胫骨骨髓腔制备骨癌痛模型；以注射加热灭活瘤细胞的SD鼠为假手术对照鼠，以正常鼠为正常对照鼠。造模后1-4周观察模型鼠自由行走痛评分、辐射热痛觉阈值[缩爪反应潜伏期（paw withdrawal latency，PWL）]和机械刺激诱发痛觉阈值[缩爪反应阈值（paw withdrawal threshold，PWT）]改变，并对痛觉行为改变明显的模型鼠进行影像学检测。结果：本方法制备模型的成瘤率为67．3％。模型鼠在造模后15d自由行走痛评分显著高于正常鼠和假手术鼠（P〈0．01）；模型鼠的模型后肢对热刺激痛觉阈值和对机械刺激诱发痛觉阈值分别在造模后21d和18d明显低于正常鼠和假手术鼠（P〈0．01），同时也明显低于模型肢对侧后肢（P〈0．05）。影像学结果显示，痛行为改变明显的模型鼠模型后肢胫骨骨质结构遭到明显破坏。结论：采用Walker256乳腺癌腹水瘤细胞可成功制备与人类骨癌痛体症相似的大鼠胫骨骨癌痛模型。     

Walker 256乳腺癌细胞构建大鼠胫骨骨癌痛模型

目的: 探讨以Walker 256大鼠乳腺癌腹水瘤细胞制备大鼠胫骨骨癌痛模型，为骨癌痛机制和治疗研究提供有用的工具。方法：以Walker 256乳腺癌细胞接种幼年雌性SD鼠腹腔制备腹水瘤细胞，将15 μl腹水瘤细胞注入雌性成年SD鼠左侧胫骨骨髓腔制备骨癌痛模型；以注射加热灭活瘤细胞的     

6%羟乙基淀粉130/0.4对患者硬膜外复合全麻诱导期肺循环的影响

Objective To observe the effect of pulmonary circulation by 6% hydroxyethyl starch 130/0.4 during induction period from epidural block combined with general anesthesia. Methods Twenty-six hepatobiliary surgical patients with ASA Ⅰ-Ⅱ, aged 32 y-59 y, weighing 54 kg-73 kg, were randomized into 2 groups(n=13): hydroxyethyl starch 130/0.4 group(HS)and complex acetic acid Ringer's solution (RL). Above-mentioned solutions were infused 7 ml/kg respectively before induction. The pulmonary circulation hemodynamic parameters such as pulmonary arterial systolic pressure (PASP), pulmonary arterial diastolic pressure (PADP), mean pulmonary artery pressure(MPAP), pulmonary artery wedge pressure(PAWP), pulmonary vascular resistance(PVR) and right ventricular stroke work(RVSW) were recorded at base value(T0), 10 min after infusion(T1), 5 min after induction(T2), 5 rain after intubation(T3), 10 rain after intubation(T4)and 20 min after intubation(T5). Results PASP、PADP、MPAP、PAWP and CVP were significantly higher in group HS at T, than the values at T0 (P<0.05); PVR in group HS was obviously lower from T1 to T5 than the value at To (P<0.05 or P<0.01); RVSW was significantly higher in two groups at T1 than base value (P<0.05), but that in group HS was lower than base value (P<0.05 or P<0.01); HR obviously decreased in two groups from T2 to T5 as compared with the value at T0 (P<0.05); MAP was lower from T3 to T5 than the value at To (P<0.05 or P<0.01). PVR was obviously lower in group HS from T1 to T5 than that in group RL (P<0.05 or P<0.01); MAP obviously increased from T2 to T5 in group HS as compared with the value in group RL(P<0.05 or P<0.01). Conclusion 6% hydroxyethyl starch 130/0.4 can obviously reduce PVR during induction pe-riod from epidural block combined with general anesthesia. In all, there is no effect on pulmonary circulation by 6% hydroxyethyl starch 130/0.4.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.     

静脉止血剂对肝癌切除术后远期预后的影响

目的 探讨术中使用静脉止血剂对肝癌切除术后的远期生存与复发的影响。 方法 选择2005至2007年本院手术切除的肝癌患者中肿瘤直径<5 cm的T_1-2N₀M₀期,肝功能Child-Pugh评分A、B级,病理切缘阴性者,共504例。用逐步回归法Cox模型分析各因素对患者远期生存复发的影响,Kaplan-Meier法分析使用静脉止血剂对患者总生存时间和无瘤生存时间的影响。 结果 所有患者中位随访时间为64 （7~72） 个月,504例患者中围术期使用过静脉止血剂者326例,未使用任何静脉止血剂者178例,使用止血剂组5年总生存率较未使用止血剂组低（61.04% vs 75.28%,P=0.002）;使用止血剂组患者5年无瘤生存率较未使用止血剂组患者低（49.08% vs 61.80%,P=0.001）。逐步回归法Cox分析表明,围术期使用静脉止血剂是影响患者术后总生存（RR=1.872,95%CI 1.298~2.702;P=0.001）和无瘤生存（RR=1.523,95%CI 1.136~2.043;P=0.005）的独立危险因素。 结论 围术期使用静脉止血剂可能会降低肝癌切除患者术后总生存时间和无瘤生存时间。     

梗阻性黄疸患者七氟烷麻醉术后苏醒时间的临床观察

目的观察梗阻性黄疸患者七氟烷麻醉术后的苏醒时间。方法60例上腹部手术患者,ASAⅠ-Ⅱ级,按血胆红素分为无黄疸对照组,轻度黄疸组,中度黄疸组,重度黄疽组,每组15例。其中黄疽组患者均为梗阻性黄疸。常规麻醉诱导后吸入1％-2％七氟烷,维持BIS值45,术毕即停吸七氟烷。同时记录从停药后至BIS值达到90的时间和唤醒时间。结果黄疸组BIS值达到90的时间和唤醒时间明显大于非黄疸对照组,但黄疸轻,中,重三组之间无明显差异。结论梗阻性黄疸患者七氟烷麻醉术后苏醒时间明显延长,胆红素水平与延长的苏醒时间无明显相关性。     

胆红素的神经毒性

胆红素的神经毒性主要与血清中游离胆红素的浓度有关.游离胆红素在脑脊液和中枢神经系统的蓄积,与血脑屏障上的转运蛋白以及机体内环境等诸多因素的影响有关.并且游离胆红素不仅对星形胶质细胞和神经元有毒性作用,还会干扰神经突触之间的神经递质的传递,同时还会损坏线粒体,导致细胞能量代谢障碍以及细胞的凋亡.本文就胆红素的神经毒性作一综述.     

高渗氯化钠羟乙基淀粉40注射液高容量血液稀释对大鼠肝脏缺血再灌注损伤的影响

Objective To investigate the effects of hypervolemic hemodilution (HH) with hypertonic saline plus hetastarch solution 40 injectio on hepatic ischemia-reperfusion (I/R) injury in rats. Methods Thirty male Wistar rats weighing 300-350 g were randomly divided into 3 groups ( n = 10 each): group I sham operation (group S); group II I/R and group Ⅲ HH. Partial liver ischemia was produced by clamping hepatic portal vein and left arteria hepatica for 30 min with atraumatic mini-clamp, followed by 2 h of reperfusion in I/R group and HH group. In HH group the animals were infused hypertonic saline plus hetastarch solution 40 injectio 10 ml/kg through vena caudalis over 30 min and then hepatic I/R was performed IS min after the infusion.The animals were killed at 2 h of reperfusion. The left liver was removed and blood sample was taken from inferior caval vein for determination of (1) serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities; (2) superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the liver; ( 3 ) microscopic examination. Results The serum ALT and AST activities and MDA content in the liver were significantly higher, SOD activity in the liver significantly lower after hepatic I/R and pathological changes in the liver severer in group I/R and HH than in group S. The serum ALT and AST activities and MDA content in the liver were significantly lower, SOD activity in the liver significantly higher after hepatic I/R and pathological changes in the liver milder in group HH than in group I/R. Conclusion Hypervolemic hemodilution with hypertonic saline plus hetastarch solution 40 injectio can ameliorate hepatic I/R injury by decreasing oxygen free radical production in rats.