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脂质体包裹对布比卡因致大鼠脊髓神经毒性的影响

Effect of encapsulation in liposomes on toxic effect of bupivacaine on spinal cord in rats
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摘要 目的评价脂质体包裹对布比卡因致大鼠脊髓神经毒性的影响。方法取鞘内置管成功的sD大鼠108只,体重200—225g,采用随机数字表法,将其随机分为6组(n=18):对照组(c组)、脂质体组(L组)、0.5%布比卡因组(B1组)、1%布比卡因组(B2组)、0.5%脂质体布比卡因组(LB1组)和1%脂质体布比卡因组(LB2组)。从鞘内置管成功第4天开始,L组、B,组、B2组、LB1组和LB2组每天分别鞘内注射脂质体、0.5%布比卡因、1%布比卡因、0.5%脂质体布比卡因和1%脂质体布比卡因各20μl,连续7d。给药结束后观察大鼠后肢形态和行走状况。采用痛敏仪测定大鼠后爪机械痛阈。痛阈测定结束后每组随机处死8只大鼠,取腰膨大处脊髓组织,采用免疫组化法计数Fos蛋白阳性细胞。痛阚测定结束后每组随机处死8只大鼠,取注射节段脊髓组织,采用流式细胞仪测定细胞凋亡情况,计算细胞凋亡率。痛阈测定结束后每组随机取2只大鼠,取L3-4节段脊髓组织,观察神经元超微结构。结果与c组比较,L组机械痛阈、Fos蛋白阳性细胞计数和细胞凋亡率差异无统计学意义(P〉0.05),B1组和LB1组Fos蛋白阳性细胞计数升高(P〈0.01),机械痛阈和细胞凋亡率差异无统计学意义(P〉0.05),B2组机械痛阈、Fos蛋白阳性细胞计数和细胞凋亡率升高,LB2组Fos蛋白阳性细胞计数和细胞凋亡率升高(P〈0.01),机械痛阈差异无统计学意义(P〉0.05);与B1组比较,LB2组机械痛阈和细胞凋亡率差异无统计学意义(P〉0.05),Fos蛋白阳性细胞计数降低,B:组机械痛阈、Fos蛋白阳性细胞计数和细胞凋亡率升高(P〈0.01);与B2组比较,LB2组机械痛阈、Fos蛋白阳性细胞计数和细胞凋亡率降低(P〈0.01);与LB1组比较,LB2组机械痛阈差异无统计学意义(P〉O.05),Fos蛋白阳性细胞计数和细胞凋亡率升高(P〈0.01)。结论脂质体包裹可减轻鞘内注射1%布比卡因对大鼠脊髓的神经毒性。 Objective To study the toxic effect of bupivacaine encapsulated in liposomes on spinal cord in rats. Methods One hundred and eight SD rats (200-225 g) in which intrathecal (IT) catheter was successfully implanted without complications were randomly divided into 6 groups ( n = 18 each) : control group (group C) ; liposome group (group L) ; 0.5% and 1.0% bupivacaine groups (groups B1 and B2 ) and 0.5% and 1.0% bupivacaine encapsulated in liposomes groups (groups LBl and LB2 ). In groups L, BI , B2, LB1 and LB2, liposome, 0.5 % bupivacaine, 1.0 % bupivacaine,0.5 % liposomal bypivacaine and 1.0 % liposomal bupivacaine 20 tzl were injected IT respectively once a day for 7 consecutive days, while in group C nothing was injected IT. Pain thresh- old was measured by mechanical stimulation of the plantar surface of hindpaw. Motor function of the hindlimbs was also assessed. The animals were sacrificed at 8 day after IT injection. The lumbar segment of the spinal cord was removed for microscopic examination, detection of neuronal apoptosis (by flow cytometry) and Fos protein expres- sion (by immuno-histochemistry). Results 1.0 % bupivacaine IT significantly increased the percentage of apoptot- ic neurons in group Bz as compared with control group. 0.5 % and 1.0 % bupivacaine IT significantly increased the number Fos protein positive ceils in group Bl and B2 as compared with group C. 1.0% bupivacaine IT induced se- vere histologic damage including shrinkage of nucleus and vacuole formation in mitochondria. Encapsulation of bupivacaine in liposomes significantly attenuated bupivacaine-induced increase in apoptosis and Fos protein expression and histologic damage in group LB2 as compared with group B2 . Conclusion The encapsulation in liposomes can decrease the neurotoxicity of 1.0 % bupivacaine administered IT in rats.
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2012年第2期173-176,共4页 Chinese Journal of Anesthesiology
基金 湖北省科技攻关基金(2002AA301D10)
关键词 布比卡因 脂质体 神经毒性 脊髓 Bupivacaine Liposomes Neurotoxicity Syndromes Spinal Cord
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