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. 2018 Dec 27;18(1):343.
doi: 10.1186/s12906-018-2414-3.

Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model

Yong Zhang  1 , Jian Chen  2 , Hua Ji  2 , Zhang-Gang Xiao  3   4 , Peiqiang Shen  5 , Lin-Hao Xu  6
Affiliations

Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model

Yong Zhang et al. BMC Complement Altern Med. .

Abstract

Background: Erectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism.

Methods: The diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay.

Results: The erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress.

Conclusion: Danshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.

Keywords: Danshen injection; Diabetes; Endoplasmic reticulum stress; Erectile dysfunction; Oxidative stress.

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Conflict of interest statement

Ethics approval and consent to participate

All procedures in this study were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experimental protocol was approved by the Ethics Committee of Hangzhou Medical College.

Consent for publication

Not Applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Danshen injection restored the body weight of diabetic rats without affecting the blood glucose level. a Body weight; b blood glucose levels before and at 2 days and 6 weeks after treatment. Data are presented as the mean ± standard error of the mean (S.E.M.) for ten rats per group. *P < 0.05; ***P < 0.001; ns, not significant
Fig. 2
Fig. 2
Danshen injection alleviated erectile dysfunction in diabetic rats. Treatment with Danshen injection for 6 weeks could improve erectile function via increasing erection times (a) but could not prolong the erection duration (b). Data are presented as the mean ± standard error of the mean (S.E.M.) for ten rats per group. *P < 0.05; ns, not significant
Fig. 3
Fig. 3
Danshen injection ameliorated morphological abnormalities of penile tissue in diabetic rats. a The morphology of penile tissue in normal rats exhibited a large, intact architecture of the corpus cavernous tissue, which is indicated by the dotted lines (i). There was significant shrinkage of the corpus cavernous body in the diabetes group (ii); however, the area of the corpus cavernous body was increased by Danshen injection (0.5 or 1 mL/kg) treatment (iii and iv). Scale bar: 200 μm. b Data represent the means ± S.E.M. for 10 sections of five rats per group. c Significant alterations of vessels (sinusoid) and smooth muscle cells in the corpus cavernous. The density of vessels, which are highlighted by the dotted lines, was surrounded by endothelial cells (indicated by the white arrow); and the number of smooth muscle cells (indicated by the black arrow) in the control group (i) was higher than that in the diabetes group (ii). Danshen injection (0.5 or 1 mL/kg) could rescue the reduction of vessel and smooth muscle cell density (iii, iv). The inset in each picture (Scale bar: 200 μm) is enlarged and displayed on the right (Scale bar: 50 μm). d, e Bar graphs represent the quantitative difference in the density of vessels (sinusoid) and smooth muscle cells. Data represent the means ± S.E.M. for 10 sections of five rats per group. *P < 0.05; **P < 0.01; ***P < 0.001
Fig. 4
Fig. 4
Danshen injection suppressed ER stress via downregulation of Grp78 and CHOP in corpus cavernous tissue. a Immunohistochemical analysis of Grp78 expression in penile tissue sections: (i) Control group; (ii) Diabetes group; (iii) Danshen injection (0.5 mL/kg) group; (iv) Danshen injection (1 mL/kg) group. b Data represent the means ± S.E.M. for five rats per group. Scale bar: 20 μm. c Immunohistochemical analysis of CHOP expression: (i) Control group; (ii) Diabetes group. (iii) Danshen treatment (0.5 mL/kg) group; (iv) Danshen treatment (1 mL/kg) group. d Data represent the means ± S.E.M. for five rats per group. Scale bar: 50 μm. e Western blot analysis of Grp78 and CHOP expression in penile tissue and (f) densitometry of the respective blots. Data are represented as the means ± S.E.M. for five rats per group, normalized to β-actin and expressed as a percentage of the control. g, h The mRNA levels of Grp78 and CHOP among the four groups (n = 5)
Fig. 5
Fig. 5
Danshen injection alleviated apoptosis. a Representative images of apoptotic cells in the corpus cavernous tissue by a TUNEL assay are shown. (i) Control group; (ii) Diabetes group; (iii) Danshen injection group (0.5 mL/kg); (iv) Danshen injection group (1 mL/kg). Hyperglycemia triggered an increase in the number of apoptotic cells (arrow), whereas Danshen injection potentially reduced the number of apoptotic cells. b Apoptotic nuclei were quantified. Data are presented as the mean ± standard error of the mean (S.E.M.). *P < 0.05; **P < 0.01. Scale bar: 20 μm. c The expression of cleaved caspase-3 was detected by western blot analysis. Cleaved caspase-3 was upregulated in the diabetes group, which was prevented by the Danshen injection. d Data are presented as the mean ± standard error of the mean (S.E.M.) for five rats per group. *P < 0.05; **P < 0.01
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References

    1. Castela A, Gomes P, Domingues VF, Paiga P, Costa R, Vendeira P, Costa C. Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction. J Diabetes. 2015;7(3):393–401. doi: 10.1111/1753-0407.12181. - DOI - PubMed
    1. Zhu LL, Zhang Z, Jiang HS, Chen H, Chen Y, Dai YT. Superparamagnetic iron oxide nanoparticle targeting of adipose tissue-derived stem cells in diabetes-associatederectile dysfunction. Asian J Androl. 2017;19(4):425-32. - PMC - PubMed
    1. Sun L, Peng FL, Yu ZL, Liu CL, Chen J. Combined sildenafil with vacuum erection device therapy in the management of diabetic men with erectile dysfunction after failure of first-line sildenafil monotherapy. In J Urol : official journal of the Japanese Urological Association. 2014;21(12):1263–1267. - PubMed
    1. Zhang XM, Shi PH, Cao SH, Yu HJ, Azad J, Ling SC. Expression changes of transforming growth factor-beta1 and thrombospondin-1 in cavernous tissues of diabetic rats. Urol Int. 2010;84(2):221–225. doi: 10.1159/000277602. - DOI - PubMed
    1. Kamenov ZA. A comprehensive review of erectile dysfunction in men with diabetes. Exp Clin Endocrinol Diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2015;123(3):141–158. - PubMed

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