黄芪多糖预先给药对大鼠鞘内注入布比卡因脊神经毒性的影响  

Effect of astragalus polysaccharides pretreatment on neurotoxicity of intrathecal bupivacaine in rats

作　　者：徐世元[1] 崔睿[1] 张旱愉[2] 王宝君[2] 张韵[2] 

机构地区：[1]南方医科大学珠江医院麻醉科,广州市510280 [2]南方医科大学附属深圳市妇幼保健院,518028

出　　处：《实用医学杂志》2010年第15期2705-2707,共3页The Journal of Practical Medicine

基　　金：国家自然科学基金(编号:30972843);深圳市医学科研基金项目(编号:200903109)

摘　　要：目的:探讨预先给予黄芪多糖是否可以减轻大鼠鞘内注入布比卡因所致脊神经毒性及其机制。方法:健康雌性SD大鼠,体重180～220g,取鞘内置管成功大鼠30只,随机分成5组(n=6)。对照组(N组):鞘内注射生理盐水30μL,腹腔注入生理盐水。2%与4%布比卡因组(2B组与4B组):鞘内分别注入2%与4%布比卡因30μL,腹腔注入生理盐水。2%与4%布比卡因黄芪多糖预处理组(2H组与4H组):鞘内分别注入2%与4%布比卡因30μL,腹腔注入黄芪多糖25mg/kg,生理盐水稀释成2mL,于鞘内给药前连续注药3d。鞘内注药后10min、20min、30min、1h、2h、4h、1d、2d、3d和4d测定甩尾反应潜伏期(TFL),用最大效应百分比MPE表示。4d后各组大鼠行断颈处死,分离背根神经节,Western blot分析caspase-9蛋白表达水平,并行病理学观察。结果:(1)各组MPE比较差异有统计学意义(P<0.05);(2)鞘内注药后10min,2B组、4B组、2H组和4H组MPE均达到峰值,2B组、2H组和4H组于鞘内注药后2h恢复至基线水平,而4B组于注药后4h方恢复至基线水平。与N组比较,2B组,4B组,2H组和4H组caspase-9蛋白表达均上调(P<0.05);与2B和4B组比较,2H组和4H组caspase-9蛋白表达降低(P<0.05);(3)病理学结果:N组大鼠背根神经节细胞形态和结构正常。2B组和4B组有部分神经细胞萎缩、空泡化。2H组和4H组神经细胞形态和结构基本正常。结论:预先给予黄芪多糖可减轻大鼠鞘内注入布比卡因的脊神经毒性,其机制可能与抑制caspase-9蛋白表达,抗神经细胞凋亡有关。Objective To investigate the effect of astragalus polysaccharides （APS） pretreatment on neurotoxicity of intrathecal bupivacaine in rats. Methods 30 rats weighting 180-220 g which were successfully intrathecally placed with PE-10 catheter were randomly divided into 5 groups （n = 6 each）. Rats in control group （Group N） received 30μL of normal saline intrathecally and intraperitoneal injection with 2 mL of normal saline. Those in 2% and 4% bupivacaine group （Group 2B and Group 4B） received 30μL of 2% or 4% bupivacaine intratheeally and intraperitoneal injection with 2 mL of normal saline. Those in 2% and 4% bupivaeaine APS pretreatment group （Group 2H and Group 4H） received 30%, of 2% or 4% bupivacaine intrathecally and pretreatment with intraperitoneal injection with 2 mL of 25 mg/kg of APS plus normal saline for 3 d. Tail-flick test were performed at 10 rain, 20 rain, 30 min, 1 h, 2 h, 4 h, 1 d, 2 d, 3 d and 4 d after intrathecal administration, and were converted to the percent of maximal possible effect （MPE）. All the rats were sacrificed 4 days later, and the dorsal root ganglia were isolated for determination of the expression of caspase-9 protein by western blot and of pathological changes. Results MPE were different among all the groups. MPE reached the peak in Groups 2B, 4B, 2H, and 4H 10 rain after the adminstration, and then reverted to the baseline in Groups 2B, 2H, and 4H after 2 h, while in Group 4H that happened after 4 h. The expressions of caspase- 9 protein in Groups 2B, 4B, 2H, and. 4H were increased significantly as compared with those in Group N, and those in Group 2H and 4H were decreased significantly as compared with those in Group 2B and 4B respectively. The neurons in Groups 2H, 4H, and N were normal, while those with the changes of cellular atrophy and vacuolization were observed in Group 2B and 4B. Conclusion APS pretreatment can reduce the neurotoxicity of intrathecal injection of bupivacaine in rats, which is related to the down-regulation of caspase-9 protei

关 键 词：黄芪多糖 布比卡因 药物毒性 预处理 CASPASE-9 

分 类 号：R614[医药卫生—麻醉学]