Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 9:13:1008269.
doi: 10.3389/fphys.2022.1008269. eCollection 2022.

Effects of electroacupuncture on bladder dysfunction and the expression of PACAP38 in a diabetic rat model

Xuke Han  1   2 , Yiding Chen  2 , Lue Ha  1 , Jiao Yang  2 , Fangzhou Wang  1 , Huizhen Chen  2 , Qian Zhou  2 , Cong Long  2 , Xianliang Qiu  3 , Qiu Chen  2
Affiliations

Effects of electroacupuncture on bladder dysfunction and the expression of PACAP38 in a diabetic rat model

Xuke Han et al. Front Physiol. .

Abstract

Objective: To explore the effects and the possible mechanism of electroacupuncture (EA) on diabetic bladder dysfunction (DBD) in streptozotocin-high fat diet (STZ-HFD) induced type 2 diabetes mellitus (T2DM) rats. Methods: The experiment was divided into Control, diabetic bladder dysfunction, electroacupuncture, and Sham electroacupuncture group. After 8 weeks of electroacupuncture intervention, the body mass, 24 h urine volume, intraperitoneal glucose tolerance test (IPGTT), and urodynamics were detected. After the wet weight of the bladder was detected, the hematoxylin-eosin (HE), Masson's trichrome, and TUNEL were used to analyze histological changes. The PACAP38 expressions in the bladder were detected by Real-time PCR and Western blot. Results: Compared to the Control group, the bladder wet weight, 24 h urine volume, blood glucose, maximum bladder capacity, bladder compliance, bladder wall thickness, the smooth muscle/collagen ratio, and apoptosis rate of the diabetic bladder dysfunction group were significantly increased. Moreover, the body mass and leak point pressure were significantly reduced. Compared with the Sham electroacupuncture group, the bladder wet weight, maximum bladder capacity, bladder compliance, bladder wall thickness, and apoptosis rate of the electroacupuncture group were significantly reduced. In contrast, the leak point pressure was increased. The PACAP38 mRNA and PACAP38 protein expression of the diabetic bladder dysfunction group were significantly lower than the Control group, while electroacupuncture treatment could upregulate PACAP38 mRNA levels and PACAP38 protein expression of diabetic bladder dysfunction model rats. Conclusion: electroacupuncture could ameliorate bladder dysfunction in the diabetic bladder dysfunction model rats by reversing bladder remodeling, which might be mainly mediated by regulating the PACAP38 level.

Keywords: cystometry; diabetic bladder dysfunction; electroacupuncture; pituitary adenylate cyclase activating polypeptide; type 2 diabetes mellitus rats.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Time flow chart of rat modeling and experimental intervention. Timeline for modeling and intervention procedures.
FIGURE 2
FIGURE 2
General characteristics of each group. (A) FBG: fasting blood glucose; (B) Body mass; (C) 24 h urine volume; (D) IPGTT: intraperitoneal glucose tolerance test; (E) Bladder weight. Control: n = 8 rats, DBD: n = 7 rats, EA: n = 7 rats, Sham EA: n = 8 rats. Results are expressed as mean ± standard error of the mean. * p < 0.01 versus the Control group, # p < 0.05 versus the Sham EA group (Student’s t-test was used to analyze the data of the FBG, and one-way ANOVA to the rest of the data).
FIGURE 3
FIGURE 3
Representative cystometry records of each group. Assessment of voiding function with cystometry. EA-treated DBD model rats tended to have normal voiding patterns. (A) A normal voiding pattern was noted in the Control group. (B) An overactive bladder pattern was noted in the DBD group. (C) The unstable spontaneous contractile bladder pattern was noted in the EA group. (D) An abnormal voiding bladder pattern was noted in the Sham EA group.
FIGURE 4
FIGURE 4
Comparison of cystometry parameters in a urodynamic test. The results of bladder wall thickness (e) in the ultrasonography test.(A) MBC: maximum bladder capacity; (B) BP: basal Pressure; (C) LPP: leakage point pressure; (D) BC: bladder compliance. Control: n = 8 rats, DBD: n = 7 rats, EA: n = 7 rats, Sham EA: n = 8 rats. Results are expressed as mean ± standard error of the mean. * p < 0.05 versus the Control group. # p < 0.05 versus the Sham EA group (one-way ANOVA).
FIGURE 5
FIGURE 5
The bladder wall thickness in each group on HE images. Representative micrographs of a thin section of the bladder wall (magnification ×50). Bar graphs show the quantitative image analysis. (A). Control group: n = 8 rats; (B). DBD group: n = 7 rats; (C). EA group: n = 7 rats; (D). Sham EA group: n = 8 rats; (E). The results of bladder wall thickness in the HE staining. Results are expressed as mean ± standard error of the mean. * p < 0.01 versus the Control group. # p < 0.01 versus the Sham EA group (one-way ANOVA).
FIGURE 6
FIGURE 6
The smooth muscle/collagen ratio in each group on Masson’s trichrome images. Digitalization images (50x) from Masson’s trichrome staining. Representative micrographs show collagen with blue staining and muscle with red staining. (A). Control group: n = 8 rats; (B). DBD group: n = 7 rats; (C). EA group: n = 7 rats; (D). Sham EA group: n = 8 rats; (E). The ratio of smooth muscle to collagen in Masson’s trichrome staining. Results are expressed as mean ± standard error of the mean. * p < 0.05 versus the Control group (one-way ANOVA). The green arrowheads indicate fiber expression.
FIGURE 7
FIGURE 7
The percentage of apoptotic cells in each group on TUNEL images. Representative micrographs show TUNEL-positive cell expression: normal nuclei showed blue light, while apoptotic nuclei showed green light (magnification ×400). Bar graphs show the quantitative image analysis. (A1-A2). Control group: n = 8 rats; (B1-B2). DBD group: n = 7 rats; (C1-C2). EA group: n = 7 rats; (D1-D2). Sham EA group: n = 8 rats; (E). The apoptotic cells percentage within the total number of cells in each area. Results are expressed as mean ± standard error of the mean. * p < 0.01 versus the Control group. # p < 0.01 versus the Sham EA group (one-way ANOVA). The yellow arrowheads indicate the apoptotic cells. The red arrowheads indicate normal cells.
FIGURE 8
FIGURE 8
The effect of EA on PACAP38 mRNA in the rat bladder measured by real-time PCR. The relative expression of PACAP38 mRNA among groups. Control: n = 8 rats, DBD: n = 7 rats, EA: n = 7 rats, Sham EA: n = 8 rats. The Results are expressed as mean ± standard error of the mean. * p < 0.01 versus the Control group. # p < 0.01 versus the Sham EA group (one-way ANOVA).
FIGURE 9
FIGURE 9
Expression of bladder PACAP38 protein in rats after the 8-week intervention (A). Western blot bands of PACAP38 protein expression. (B). Bar graphs show the quantitative analysis for PACAP38 protein expression. Control: n = 8 rats, DBD: n = 7 rats, EA: n = 7 rats, Sham EA: n = 8 rats. Results are expressed as mean ± standard error of the mean. * p < 0.05 versus the Control group. # p < 0.05 versus the Sham EA group (one-way ANOVA).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Arimura A. (1998). Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn. J. Physiol. 48 (5), 301–331. PubMed PMID: 9852340. 10.2170/jjphysiol.48.301 - DOI - PubMed
    1. Banki E., Degrell P., Kiss P., Kovacs K., Kemeny A., Csanaky K., et al. (2013). Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy. Peptides 42, 125–130. PubMed PMID: 23416022. 10.1016/j.peptides.2013.02.002 - DOI - PubMed
    1. Bars-Cortina D., Riera-Escamilla A., Gou G., Pinol-Felis C., Motilva M. J. (2019). Design, optimization and validation of genes commonly used in expression studies on DMH/AOM rat colon carcinogenesis model. Peerj 7, e6372. PubMed PMID: 30713822. 10.7717/peerj.6372 - DOI - PMC - PubMed
    1. Boga M. S., Haliloglu A. H., Gulpinar O., Ozayar A., Sonmez M. G., Pinarli F. A., et al. (2020). Neonatal bladder-derived mesenchymal stem cells ameliorate bladder dysfunction in diabetic rat models. Urol. J. 17 (4), 413–421. PubMed PMID: 32619015. 10.22037/uj.v0i0.5504 - DOI - PubMed
    1. Braas K. M., May V., Zvara P., Nausch B., Kliment J., Dunleavy J. D., et al. (2006). Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290 (4), R951–R962. PubMed PMID: 16322346. 10.1152/ajpregu.00734.2005 - DOI - PMC - PubMed

Grants and funding

The study was partly supported by grants from the Youth Science and Technology Innovation Project of Science and Technology Department of Sichuan Province (no. 2022084) and Sichuan Characteristic Specialty Construction Project of Traditional Chinese Medicine (no. CYW2022045).

LinkOut - more resources

  NODES
innovation 1
Note 4
Project 2
twitter 2