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β2-肾上腺素受体激动剂在糖尿病周围神经病变中的潜在治疗作用。

β2-Adrenoceptor agonists as potential therapeutic drugs in diabetic peripheral neuropathy.

机构信息

Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Egypt.

Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Egypt.

出版信息

Eur J Pharmacol. 2015 Jan 5;746:89-95. doi: 10.1016/j.ejphar.2014.11.004. Epub 2014 Nov 13.

DOI:10.1016/j.ejphar.2014.11.004
PMID:25445052
Abstract

OBJECTIVES

the aim of the current study was to assess the effect of a β2-adrenoceptor agonist; namely salbutamol, on hyperalgesic as well as nerve dysfunction components of diabetic peripheral neuropathy.

MATERIAL AND METHODS

the present study was conducted on 60 male Wistar albino rats divided into six groups. Groups I and II were normal control rats injected by a single i.p. injection of normal saline and received 2% gum acacia (Group I) or salbutamol (Group II) for six weeks, starting one week following saline injection. Groups III-VI: rats that were rendered diabetic by a single i.p. injection of STZ and received either 2% gum acacia, salbutamol, salbutamol and propranolol or salbutamol and atenolol, respectively daily orally for six weeks, starting one week following STZ injection.

RESULTS

vehicle-treated diabetic rats exhibited: significant sciatic nerve dysfunction in the form of significantly prolonged distal latency and significantly decreased maximum peak and peak to peak amplitude of compound muscular action potential, significant thermal and mechanical hyperalgesia evidenced by significant decrease in hot plate latency, tail-flick latency and vocalization threshold, respectively. Salbutamol administration improved nerve dysfunction as well as thermal and mechanical hyperalgesia. These effects of salbutamol are most likely mediated by β2-adrenoceptors evidenced by significant abolishment of salbutamol effects after administration of the non-selective rather than the selective beta blockers; propranolol and atenolol, respectively.

CONCLUSIONS

chronic administration of salbutamol could ameliorate DPN, an effect which is most likely mediated by β2-adrenoceptors.

摘要

目的

本研究旨在评估β2-肾上腺素受体激动剂(即沙丁胺醇)对糖尿病周围神经病变的痛觉过敏和神经功能障碍成分的影响。

材料和方法

本研究共纳入 60 只雄性 Wistar 白化大鼠,分为 6 组。第 I 组和第 II 组为正常对照组,经腹腔单次注射生理盐水,分别给予 2%阿拉伯胶(第 I 组)或沙丁胺醇(第 II 组),于生理盐水注射后第 1 周开始,连续 6 周。第 III-VI 组:大鼠经腹腔单次注射链脲佐菌素(STZ)致糖尿病,分别给予 2%阿拉伯胶、沙丁胺醇、沙丁胺醇和普萘洛尔或沙丁胺醇和阿替洛尔,每日口服,于 STZ 注射后第 1 周开始,连续 6 周。

结果

未治疗的糖尿病大鼠表现出明显的坐骨神经功能障碍,表现为明显延长的远端潜伏期和明显降低的复合肌肉动作电位的最大峰值和峰值到峰值幅度;明显的热痛觉过敏和机械痛觉过敏,表现为明显缩短热板潜伏期、尾巴闪烁潜伏期和发声阈值。沙丁胺醇治疗改善了神经功能障碍以及热痛觉过敏和机械痛觉过敏。沙丁胺醇的这些作用很可能是通过β2-肾上腺素受体介导的,因为给予非选择性而非选择性β受体阻滞剂(分别为普萘洛尔和阿替洛尔)后,沙丁胺醇的作用明显被消除。

结论

慢性给予沙丁胺醇可能改善糖尿病周围神经病变,这种作用很可能是通过β2-肾上腺素受体介导的。

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