Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress
Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress
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二亚苯基碘通过减轻氧化应激来减轻糖尿病神经病变大鼠模型中布比卡因引起的坐骨神经损伤
DOI：
10.1213/ane.0000000000002186
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发表时间：
2017-08
影响因子：
5.7
通讯作者：
Xu Shi-Yuan
中科院分区：
文献类型：
--
作者：
Ji Zhong-Hua;Liu Zhong-Jie;Liu Zi-Ting;Zhao Wei;Williams Brian A.;Zhang Hong-Fei;Li Le;Xu Shi-Yuan
背景：在糖尿病神经病变（DN）大鼠模型中，氧化应激增加与局部麻醉诱导的神经损伤有关。本研究探讨NADPH氧化酶（NOX）抑制剂二苯二酮（DPI）氯对布比卡因诱导的DN大鼠坐骨神经损伤的影响。方法：采用高脂饲料喂养和注射链脲佐菌素建立大鼠DN模型。通过测试(i)血糖，（ii）后爪对von Frey单丝（VF）的异常性痛反应，（iii）爪脱脱热潜伏期（PWTL）和（iv）神经传导速度（NCV）来证实模型。布比卡因（Bup, 0.2 mL, 5 mg/mL）阻断右侧坐骨神经。坐骨阻滞前24小时和30分钟皮下注射DPI （1 mg/kg）。阻滞后24小时，评估NCV、各种活性氧和Caspase-3以确定坐骨神经损伤程度。结果：成功建立DN大鼠模型。与DN对照组相比，VF反应后阻滞值（DN- con, 16.5±1.3 g; DN + Bup, 19.1±1.5 g, P < 0.001）和PWTL显著升高（DN- con, 13.3±1.1 s; DN + Bup, 14.6±1.1 s, P = 0.028）；布比卡因治疗组坐骨神经NCV明显降低（DN- con, 38.8±2.4 m/s, DN + Bup, 30.5±2.0 m/s, P = 0.003），坐骨神经损伤（以轴突面积表示）更为严重（DN- con, 11.6±0.3 &mgr;m2, DN + Bup, 7.5±0.3 &mgr;m2, P < 0.001）。此外，DPI治疗显著改善了神经功能（VF反应，17.3±1.3 g； PWTL, 13.4±1.1秒；NCV, 35.6±3.1 m/s），减轻了轴突面积的损失（9.6±0.3 &mgr;m2）。与DN + Bup组（无DPI）相比，DN + Bup + DPI组的脂质过氧化物和氢过氧化物水平以及NOX2、NOX4和Caspase-3的蛋白表达均显著降低（P < 0.05）。结论：在高脂肪饮食/链脲佐菌素诱导的DN模型中，皮下注射DPI似乎可以保护布比卡因阻断的坐骨神经的功能和神经组织学损伤。
BACKGROUND: Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats. METHODS: A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury. RESULTS: The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P < .001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 &mgr;m2, DN + Bup, 7.5 ± 0.3 &mgr;m2, P < .001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 &mgr;m2). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P < .05). CONCLUSIONS: Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin–induced DN model.
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影响因子：
7.4
作者：
S. Llesuy;P. Evelson;B. González-Flecha;J. Peralta;M. Carreras;J. Poderoso;A. Boveris
通讯作者：
S. Llesuy;P. Evelson;B. González-Flecha;J. Peralta;M. Carreras;J. Poderoso;A. Boveris
影响因子：
4.3
作者：
Genet, S;Kale, RK;Baquer, NZ
通讯作者：
Baquer, NZ
脱氧野尻霉素多糖通过调节肝糖代谢对高脂饮食和链脲佐菌素诱导的糖尿病小鼠的降血糖作用
影响因子：
5.1
作者：
Li, You-gui;Ji, Dong-feng;Lv, Zhi-qiang
通讯作者：
Lv, Zhi-qiang
DOI：
10.1111/j.1749-6632.2002.tb04665.x
发表时间：
2002-01-01
期刊：
CELL SIGNALING, TRANSCRIPTION, AND TRANSLATION AS THERAPEUTIC TARGETS
影响因子：
--
作者：
Agthong, S;Tomlinson, DR
通讯作者：
Tomlinson, DR
DOI：
10.1042/bj2620575
发表时间：
1989-09
期刊：
The Biochemical journal
影响因子：
--
作者：
Juliet A. Ellis;Andrew R. Cross;O. T. Jones
通讯作者：
Juliet A. Ellis;Andrew R. Cross;O. T. Jones