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小檗碱通过抑制糖尿病脑病大鼠 Rho/ROCK 通路升高线粒体膜电位并减少活性氧。

Berberine elevates mitochondrial membrane potential and decreases reactive oxygen species by inhibiting the Rho/ROCK pathway in rats with diabetic encephalopathy.

机构信息

Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

出版信息

Mol Pain. 2021 Jan-Dec;17:1744806921996101. doi: 10.1177/1744806921996101.

Abstract

OBJECTIVES

Diabetic encephalopathy (DE) is a serious complication of diabetes mainly occurring in the elderly patients. Berberine (BBR) is an isoquinoline alkaloids extracted from Coptis chinensis that is applied in the treatment of diabetes clinically. This study explored the possible mechanism of BBR in relieving DE.

METHODS

Wistar rats were injected with streptozotocin and fed a high fat diet to establish the model of DE. The model rats were treated with BBR. The body weight, blood glucose and insulin of rats were measured, and Morris water maze test was conducted to evaluate the learning and memory abilities. The pathological conditions of cortical tissues were detected. The cortical mitochondria membrane potential (MMP) and reactive oxygen species (ROS) were monitored. The expressions of Rho/ROCK pathway-related genes of rat cortex were detected. The changes of MMP and ROS were detected after the treatment of Rho/ROCK pathway activator.

RESULTS

The body weight of model rats changed little, and levels of blood glucose and insulin were increased. The spatial learning and memory abilities were impaired, with disordered cortical neurons, and obvious neurons apoptosis and glia proliferation. BBR alleviated cognitive dysfunction and pathological damage in rats with DE. BBR enhanced cortical MMP and suppressed ROS. BBR treatment inhibited the Rho/ROCK pathway. Activation of the Rho/ROCK pathway reversed the effects of BBR on MMP and ROS.

CONCLUSION

BBR elevated MMP and reduced ROS in rats with DE by inhibiting the Rho/ROCK pathway. This study may offer novel insights for the management of DE.

摘要

目的

糖尿病脑病(DE)是一种严重的糖尿病并发症,主要发生在老年患者中。小檗碱(BBR)是从黄连中提取的一种异喹啉生物碱,临床上用于治疗糖尿病。本研究探讨了 BBR 缓解 DE 的可能机制。

方法

Wistar 大鼠注射链脲佐菌素并给予高脂肪饮食,建立 DE 模型。模型大鼠给予 BBR 治疗。测量大鼠的体重、血糖和胰岛素,进行 Morris 水迷宫试验评估学习和记忆能力。检测皮质组织的病理状况。监测皮质线粒体膜电位(MMP)和活性氧(ROS)。检测大鼠皮质 Rho/ROCK 通路相关基因的表达。检测 Rho/ROCK 通路激活剂处理后 MMP 和 ROS 的变化。

结果

模型大鼠体重变化不大,血糖和胰岛素水平升高。空间学习和记忆能力受损,皮质神经元排列紊乱,神经元凋亡和胶质细胞增生明显。BBR 缓解了 DE 大鼠的认知功能障碍和病理损伤。BBR 增强了皮质 MMP 并抑制了 ROS。BBR 处理抑制了 Rho/ROCK 通路。Rho/ROCK 通路的激活逆转了 BBR 对 MMP 和 ROS 的影响。

结论

BBR 通过抑制 Rho/ROCK 通路,提高了 DE 大鼠的 MMP 并降低了 ROS。本研究为 DE 的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a31/7934021/9aa5c88b591e/10.1177_1744806921996101-fig1.jpg

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