摘要
目的 观察鞘内注射不同浓度多塞平后大鼠运动功能变化规律,并通过脊髓形态学观察和脊髓凋亡细胞检测进一步探讨多塞平脊髓毒性机理.方法 24只鞘内置管大鼠随机分为N组、D10组、D20组和D40组,分别鞘内注射生理盐水、10mmol/L、20mmol/L和40mmol/L多塞平,改良Tarlov法评价大鼠运动功能：6h后取大鼠脊髓行光镜形态学观察;TUNEL染色法检测脊髓组织凋亡细胞的表达.结果 ①鞘内注射10～40mmol/L多塞平10min后,均能阻断大鼠后肢运动功能（P＜0.01）;D10,D20组分别于给药后90min和120min恢复到给药前水平;D40组运动功能于各时间点与N组及给药前相比,仍有明显差异（P＜0.05）.②形态学观察：各多塞平组出现了不同程度的结构改变.③TUNEL染色阳性凋亡细胞数在各多塞平组均高于N组（P＜0.05）,但D40组与D20组比较差异无统计学意义.结论 大鼠鞘内注射多塞平可产生浓度依赖性神经阻滞作用和脊髓毒性.细胞凋亡机制参与了多塞平脊髓毒性作用.
Objective To study the neurotoxieity of doxepin in spinal cords according to the changes of neu- robehavioral and microstructure after intratheeal （ i. th） administration in rats, and investigate apoptosis in spinal cords so as to explore the mechanism of Spinal neurotoxicity of doxepin intrathecal administration. Methods Twenty-four male Wister rats suecessfldly implanted with microspinal catheter were randomly divided into group N ,group D40, D20,and group D10,in which the rats received normal saline,40,20,and 10mmol/L doxepin 0.2ul/g i. th respeetively（n = 6）. The motor function was evaluated hy modified Tarlov score. The enlarged lumber spinal cords were examined by light microscope and apoptosis was by TUNEL assay 6 hour later. Results ①Doxepin 10 - 40 mmol/L i. th produced a complete motor blockage in i0 rain after administration（ P 〈 0.01 ） , and motor function in group D10 and D20 was recovered from blockage in 90 min and 120 min, respectively, while Group D40 did not recover in 6h. ②There were some histopathology changes in doxepin groups, vacuolization and necrosis were lound in nuclear of some neurons in a dose-dependent manner. ③The positive cells with TUNEL staining in doxepin groups were higher than that of group N （ P 〈 0.05 ）. Conclusion Intrathecal doxpin can produce dose-dependent spinal anesthesia and neurotoxicity. Apoptosis may be one of the mechanisms of doxepin toxicity.
出处
《潍坊医学院学报》
2011年第2期124-126,共3页
Acta Academiae Medicinae Weifang
关键词
多塞平
鞘内注射
神经毒性
凋亡
Doxepin
lntratheeal injection
Neurotoxicity
Apoptosis
