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

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.

CGRP protects bladder smooth muscle cells stimulated by high glucose through inhibiting p38 MAPK pathway in vitro.

This study aimed to explore the effect of calcitonin gene-related peptide (CGRP) on bladder smooth muscle cells (BSMCs) under high glucose (HG) treatment in vitro. BSMCs from Sprague-Dawley rat bladders were cultured and passaged in vitro. The third-generation cells were cultured and divided into control group, HG group, HG + CGRP group, HG + CGRP + asiatic acid (AA, p-p38 activator) group, CGRP group, AA group, HG + CGRP + CGRP-8-37 (CGRP receptor antagonist) group and HG + LY2228820 (p38 MAPK inhibitor) group. The cell viability, apoptosis, malondialdehyde (MDA) and superoxide dismutase (SOD) levels of BSMCs were observed by the relevant detection kits. The expressions of α-SM-actin, p38 and p-p38 were detected by qRT-PCR or Western blot analysis. Compared with the control group, the cell viability, SOD and α-SM-actin levels of BSMCs were decreased and apoptotic cells, MDA and p-p38 levels were increased after HG treatment, while these changes could be partly reversed when BSMCs were treated with HG and CGRP or LY2228820 together. Moreover, AA or CGRP-8-37 could suppress the effect of CGRP on BSMCs under HG condition. Our data indicate that CGRP protects BSMCs from oxidative stress induced by HG in vitro, and inhibit the α-SM-actin expression decrease through inhibiting the intracellular p38 MAPK signaling pathway.