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米诺环素可降低2型糖尿病性神经病变大鼠模型脊髓中的促炎和氧化应激标志物,并改善坐骨神经的形态变化。

Minocycline reduces proinflammatory and oxidative stress markers in the spinal cord and morphology changes in sciatic nerve of Type 2 diabetic neuropathy rat model.

作者信息

Ab Hamid Norhamidar, Omar Norsuhana, Ismail Che Aishah Nazariah, Long Idris

机构信息

School of Health Sciences, Universiti Sains Malaysia, Health Campus Kubang Kerian, 16150 Kota Bharu, Kelantan Malaysia.

School of Medical Sciences, Universiti Sains Malaysia, Health Campus Kubang Kerian, 16150 Kota Bharu, Kelantan Malaysia.

出版信息

Diabetol Int. 2025 Mar 19;16(3):483-492. doi: 10.1007/s13340-025-00811-3. eCollection 2025 Jul.

Abstract

AIM

This study investigated the effects of minocycline on proinflammatory cytokines, oxidative stress marker levels in the spinal cord and sciatic nerve morphology in Type 2 diabetic (T2DM) neuropathy rats.

METHODS

Male Sprague Dawley rats were randomly assigned to six groups ( = 14 per groups): Control (C), T2DM control (STZ), T2DM treated with minocycline 40 mg/kg (STZ + M40) and 80 mg/kg (STZ + M80), T2DM treated with gabapentin (STZ + G10) and non-painful T2DM neuropathy (NPDN). T2DM was induced in obese rats using a combination of high fat diet (HFD) and low-dose streptozotocin (STZ) (40 mg/kg) injection. Then, the neuropathic pain behaviour, body weight and blood biochemical analysis were performed. Rats were sacrificed and the spinal cord and sciatic nerve were collected for ELISA and histology examination.

RESULTS

T2DM rat groups were significantly increased body weight after 6 weeks but significantly reduced from 8 until 9 weeks compared to control group ( < 0.05). The fasting blood glucose (FBG) level in all T2DM groups were significantly higher on day 3, day 14, and day 22 compared to control group ( < 0.05) consistent with HbA1c levels. T2DM groups also significantly increased MDA, TNF-α, IL-1β and C-Reactive Protein (CRP) but decreased SOD and Catalase levels in the spinal cord compared to control group ( < 0.05). T2DM groups also showed significant abnormal morphology changes in the sciatic nerve compared to control group ( < 0.05). Minocycline dependent on doses and gabapentin in T2DM rat significantly alleviated all these effects.

CONCLUSION

These findings suggest the neuroprotective effects of minocycline on T2DM neuropathy.

摘要

目的

本研究调查了米诺环素对2型糖尿病(T2DM)神经病变大鼠脊髓中促炎细胞因子、氧化应激标志物水平及坐骨神经形态的影响。

方法

将雄性Sprague Dawley大鼠随机分为六组(每组n = 14):对照组(C)、T2DM对照组(STZ)、用40 mg/kg米诺环素治疗的T2DM组(STZ + M40)和80 mg/kg米诺环素治疗的T2DM组(STZ + M80)、用加巴喷丁治疗的T2DM组(STZ + G10)和无痛性T2DM神经病变组(NPDN)。使用高脂饮食(HFD)和低剂量链脲佐菌素(STZ)(40 mg/kg)注射联合诱导肥胖大鼠发生T2DM。然后,进行神经病理性疼痛行为、体重和血液生化分析。处死大鼠,收集脊髓和坐骨神经进行ELISA和组织学检查。

结果

与对照组相比,T2DM大鼠组在6周后体重显著增加,但在8至9周时显著降低(P < 0.05)。与对照组相比,所有T2DM组在第3天、第14天和第22天的空腹血糖(FBG)水平均显著更高(P < 0.05),与糖化血红蛋白(HbA1c)水平一致。与对照组相比,T2DM组脊髓中的丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和C反应蛋白(CRP)也显著增加,但超氧化物歧化酶(SOD)和过氧化氢酶水平降低(P < 0.05)。与对照组相比,T2DM组的坐骨神经也显示出明显的形态异常变化(P < 0.05)。在T2DM大鼠中,米诺环素剂量依赖性地以及加巴喷丁显著减轻了所有这些影响。

结论

这些发现表明米诺环素对T2DM神经病变具有神经保护作用。

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