右美托咪定加重罗哌卡因引起的糖尿病大鼠坐骨神经损伤

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Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats

背景与目的

前期研究表明,右美托咪定在区域神经阻滞中对局部麻醉剂引起的神经损伤具有保护作用。而在糖尿病背景下是否也存在这种潜在的保护作用尚不清楚。

方  法

成年雄性SD大鼠腹腔内注射链脲佐菌素建立糖尿病模型。对照组和糖尿病组大鼠(每组n=8)在坐骨神经周围注射0.5%罗哌卡因、20 ug/kg右美托咪定(单用和联用)或生理盐水(均为0.2 ml),测定感觉和运动神经阻滞持续时间及运动神经传导速度。在注射后第7天收集坐骨神经,用光镜和电子显微镜进行评估或用于促炎细胞因子的测量。

结 果  

在对照组非糖尿病大鼠中,罗哌卡因和右美托咪定单用或联用不会造成神经纤维损伤。而在糖尿病大鼠中,右美托咪定加重了罗哌卡因引起的严重神经纤维损伤,并表现为MNCV减慢、轴突密度降低、髓鞘内外径比(G比值)降低。电子显微镜可观察到脱髓鞘改变、轴突消失和空泡形成。神经白细胞介素-1β和肿瘤坏死因子-α也相应增加。

结 论

0.5%罗哌卡因会引起糖尿病大鼠坐骨神经严重损伤,并且大剂量的右美托咪定会显著加重这种损伤。尽管本研究中所使用的右美托咪定剂量远高于临床实践中使用的剂量,但我们的试验数据表明,进一步研究评估罗哌卡因(单用和联用右美托咪定)用于糖尿病患者周围神经阻滞是有必要的。

原始文献摘要

Yu ZY, Geng J, Li ZQ, et al. Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats.[J].BrJAnaesth 2019,122(1):141-149. DOI: 10.1016/ j.bja.2018.08.022.

Background: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.

Methods: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of strep-tozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 ug kg-1(alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements.

Results: Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fifibre damage in control non diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen.

Conclusions: Ropivacaine 0.5% causes signifificant sciatic nerve injury in diabetic rats that is greatly potentiated by highdose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted

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翻译:冯玉蓉  编辑:何幼芹  审校:王贵龙

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