鞘内注射重比重布比卡因对糖尿病神经病变大鼠脊髓神经元凋亡的影响

Effect of intrathecal hyperbaric bupivacaine on spinal cord neurons apoptosis in diabetic neuropathic rats

目的探讨鞘内注射重比重布比卡因对糖尿病神经病变大鼠脊髓神经元凋亡的影响。方法健康雄性SD大鼠32只，体重220-300g，随机取8只设为对照组（C组），其余大鼠以腹腔注射1％链脲佐菌素（STZ）60mg／kg制备大鼠糖尿病神经病变模型。C组和糖尿病神经病变模型大鼠实施鞘内置管。将鞘内置管成功的糖尿病神经病变大鼠采用随机数字表法随机分为三组：重比重布比卡因组（HB组）、等比重布比卡因组（IB组）和葡萄糖组（G组），每组8只。C组和HB组大鼠鞘内注射重比重0．75％布比卡因10μl，IB组给予等比重0．75％布比卡因10μl，G组给予10％葡萄糖10μl，1次／天，连续3d。于制备糖尿病模型前（T1）、鞘内注射给药前（T2）、鞘内给药后第1天（T3）、第2天（T4）、第3天（T5）及结束给药后第4天（T6）时测定大鼠右后爪机械缩足反射阈值（PWT）；T3～T5时分别记录大鼠每次给药2min后运动阻滞持续时间；瓦时处死大鼠，取腰膨大处的脊髓组织，HE染色，光镜下观察病理学结果；并采用TUNEL法检测脊髓神经元凋亡的情况。结果与HB组比较，C组和IB组大鼠运动阻滞时间明显缩短，脊髓凋亡神经元明显减少（P〈0．05）。与T1时比较，T2～T5时HB组、IB组和G组PWT明显降低（P〈0．05）。与T6时比较，T2～T5时HB组PWT明显降低（P〈0．05）；G组未出现运动阻滞及未见脊髓凋亡神经元。结论鞘内注射重比重布比卡因可促进糖尿病神经病变大鼠脊髓神经元的凋亡。

Objective To investigate the effect of intrathecal hyperbaric bupivacaine on spinal cord neurons apoptosis in diabetic neuropathic rats. Methods Thirty-two healthy male Sprague-Dawley rats weighing 220-300 g,8 normal rats randomly served as control group （group C）, the other rats were intraperitoneal injection 1% streptozotocin （STZ） 60 mg/kg to induce diabetic neuropathic （DN）,and last induced thirty-seven diabetic neuropathic rats. group C and diabetic neuropathic rats administer intrathecal catheter,respectively. Twenty-four rats in which DN was successfully intrathecal catheter were randomly divided into 3 groups （n=8） ：hyperbaric bupivaeaine group （group HB）, isobaric bupivacaine group （group IB）, glucose group （group G）. Hyperbaric bupivacaine 10μl were injected intrathecally in groups C and HB respectively, isobaric lidocaine 10μl were injected intrathe cally in group IB, 10% glucose 10 μl were injected intrathecally in group G, once daily for 3d. After rats each administration 2 min,motor block duration were recorded;The paw withdrawal threshold to von Frey filament stimulation （PWT） were measured before induced diabetes model （T1）, before injected intrathecally （T2）, after 30 min administered 1 d （T3）, 2 d （T4）, 3 d （T5） and end administered 4 d （T6）. All rats were sacrificed at T6 and their lumbar intumescential spinal cord tissue were removed for microscopic examination. And using TUNEL assay to measure spinal neuronal apoptosis. Results PWT was lower at T2-5 in groups HB, IB and G comparing with T1 （P〈0.05）. Comparing with group C, the motor block duration was significantly prolonged（P〈0. 05）and spinal cord neuronal apoptosis cells were increased（P〈0. 05） in group HB. Comparing with group IB, the motor block duration was significantly prolonged（P〈0.05）and spinal cord neuronal apoptosis cells were increased （P〈0. 05） in group HB,too. PWT was increased at T6 in group HB at T2-T5 （P〈0. 05）. Group G did not appear motor block and spinal cord neuronal apoptosis. Conclusion Intrathecally hyperbaric bupivaeaine can promote spinal cord neuronal apoptosis in diabetic neuropathic rats.