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咖啡因通过神经保护作用改善糖尿病大鼠的膀胱功能。

Caffeine improves bladder function in diabetic rats via a neuroprotective effect.

作者信息

Xue Jun, Liu Yadong, Zhang Sichong, Ding Liucheng, Shen Baixin, Shao Yunpeng, Wei Zhongqing

机构信息

Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.

出版信息

Exp Ther Med. 2021 May;21(5):501. doi: 10.3892/etm.2021.9932. Epub 2021 Mar 17.

Abstract

Diabetic cystopathy (DCP) is one of the most common complications of diabetes mellitus (DM). A previous study reported that caffeine may improve bladder dysfunction in rats with DM. The aim of the present study was to investigate the mechanisms behind the capacity for caffeine to improve bladder function in rats with DM. Sprague Dawley rats were divided into four groups: control, caffeine, DM and DM plus caffeine treatment (DM + caffeine). Bladder function was measured by urodynamic analyses. The levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and calcitonin gene-related peptide (CGRP) in the bladder tissue were detected by ELISA. Apoptosis in the dorsal root ganglion (DRG) was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, cleaved caspase-3, caspase-9 and cleaved caspase-9 proteins in the DRG were detected by western blotting. Following treatment with caffeine, the urination time and micturition interval of rats with DM were improved, the bladder wet weight was decreased, and the maximum voiding pressure was increased. Relative to that in the DM group, the expression levels of NGF, BDNF and CGRP in the bladder tissue of DM + caffeine rats increased; cellular apoptosis in the DRG of DM + caffeine rates decreased; and the expression levels of Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 proteins in the DRG of DM + caffeine rats were restored to a certain extent. In conclusion, caffeine promotes bladder function in rats with DM through a protective effect on DRG.

摘要

糖尿病性膀胱病(DCP)是糖尿病(DM)最常见的并发症之一。先前的一项研究报道,咖啡因可能改善糖尿病大鼠的膀胱功能障碍。本研究的目的是探讨咖啡因改善糖尿病大鼠膀胱功能的机制。将Sprague Dawley大鼠分为四组:对照组、咖啡因组、糖尿病组和糖尿病加咖啡因治疗组(DM + 咖啡因组)。通过尿动力学分析测量膀胱功能。采用酶联免疫吸附测定法检测膀胱组织中神经生长因子(NGF)、脑源性神经营养因子(BDNF)和降钙素基因相关肽(CGRP)的水平。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测背根神经节(DRG)中的细胞凋亡。通过蛋白质印迹法检测DRG中B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱天冬酶-3、裂解的半胱天冬酶-3、半胱天冬酶-9和裂解的半胱天冬酶-9蛋白的表达水平。用咖啡因治疗后,糖尿病大鼠的排尿时间和排尿间隔得到改善,膀胱湿重降低,最大排尿压力增加。与糖尿病组相比,DM + 咖啡因组大鼠膀胱组织中NGF、BDNF和CGRP的表达水平升高;DM + 咖啡因组大鼠DRG中的细胞凋亡减少;DM + 咖啡因组大鼠DRG中Bcl-2、Bax、裂解的半胱天冬酶-3和裂解的半胱天冬酶-9蛋白的表达水平在一定程度上恢复。总之,咖啡因通过对DRG的保护作用促进糖尿病大鼠的膀胱功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b69b/8005692/69e8d0307110/etm-21-05-09932-g00.jpg

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