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小檗碱改善糖尿病神经病变:PKC 通路对 TRPV1 的调节。

Berberine Ameliorates Diabetic Neuropathy: TRPV1 Modulation by PKC Pathway.

机构信息

1 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, Jiangsu, P. R. China.

出版信息

Am J Chin Med. 2017;45(8):1709-1723. doi: 10.1142/S0192415X17500926. Epub 2017 Nov 9.

Abstract

In recent years, berberine has increasingly become a topic of research as a treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications of diabetes that seriously affect patients' life quality and longevity, among which diabetic neuropathy and the consequent acute pain are the most common. In this study, we established STZ-induced diabetic models to observe whether berberine, a main constitute of Coptis chinensis Franch which has shown good hypoglycemic effects, could relieve diabetes-induced pain and explored its possible mechanism in rats and mice. Behavior assays showed increasing mechanical allodynia and thermal hyperalgesia thresholds by the Von Frey test and tail flick test during the treatment of berberine. It was found that the administration of berberine (20, 60 mg/kg; 30, 90 mg/kg) suppressed the expression of PKCε and TRPV1 which could be activated by hyperglycemia-induced inflammatory reaction. Our results also presented its capability to reduce the over expression of TNF-[Formula: see text] in diabetic rats and mice. TNF-[Formula: see text] is an inflammatory cytokine, which is closely related to diabetic peripheral neuropathy (DPN). Consequently, we supposed that berberine exerts its therapeutic effects in part by suppressing the inflammatory process and blocking the PKC pathway to inhibit TRPV1 activation, which damages neurons and causes diabetic pain.

摘要

近年来,由于黄连素具有修复功能,可以恢复受损的胰岛β细胞,因此越来越多地成为治疗糖尿病的研究课题。然而,正是糖尿病的并发症严重影响了患者的生活质量和寿命,其中糖尿病性神经病变和随之而来的急性疼痛最为常见。在本研究中,我们建立了 STZ 诱导的糖尿病模型,以观察黄连的主要成分黄连素是否可以缓解糖尿病引起的疼痛,并在大鼠和小鼠中探索其可能的机制。行为学检测显示,在用弗氏绒毛测定仪和尾巴敲击试验进行黄连素治疗时,机械性痛觉过敏和热痛觉过敏阈值增加。研究发现,黄连素(20、60mg/kg;30、90mg/kg)的给药抑制了 PKCε和 TRPV1 的表达,PKCε和 TRPV1 可被高血糖诱导的炎症反应激活。我们的结果还表明,它能够减少糖尿病大鼠和小鼠中 TNF-[Formula: see text]的过度表达。TNF-[Formula: see text]是一种炎症细胞因子,与糖尿病周围神经病变(DPN)密切相关。因此,我们推测黄连素通过抑制炎症过程和阻断 PKC 通路来抑制 TRPV1 的激活,从而发挥其治疗作用,TRPV1 的激活会损害神经元并导致糖尿病疼痛。

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