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丹参注射液通过抑制链脲佐菌素诱导的糖尿病大鼠模型内质网应激激活对勃起功能障碍的保护作用。

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

机构信息

Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.

Faculty of Basic Medicine, Hangzhou Medical College, |No. 481 Binwen Road, Binjiang District, Hangzhou, 310053, Zhejiang, China.

出版信息

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

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.

摘要

背景

勃起功能障碍(ED)是糖尿病的常见并发症。本研究旨在探讨丹参注射液对链脲佐菌素(STZ)诱导的糖尿病大鼠模型 ED 的有益作用及其潜在机制。

方法

雄性 Sprague-Dawley 大鼠腹腔内注射 60mg/kg STZ 建立糖尿病大鼠模型。糖尿病大鼠分别腹腔内注射丹参溶液(0.5 或 1mL/kg/天)或等体积生理盐水 6 周。年龄匹配的大鼠作为对照组。6 周后,评估勃起功能和海绵体组织学形态。测量阴茎组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和活性氧(ROS)水平等氧化应激指标。免疫组化、免疫印迹和 RT-PCR 检测葡萄糖调节蛋白 78(Grp78)和生长停滞和 DNA 损伤诱导基因 153(GADD153/CHOP)的表达水平。TUNEL 法检测细胞凋亡。

结果

糖尿病大鼠的勃起次数明显少于对照组。丹参注射液可通过增加勃起次数改善勃起功能。丹参注射液还可改善海绵体的形态异常,减少凋亡细胞数量,并抑制阴茎组织中 caspase-3 的激活,同时下调内质网应激标志物 Grp78 和 CHOP。丹参注射液可增加糖尿病大鼠 SOD 活性,降低 ROS 和 MDA 水平,表明其抑制氧化应激。

结论

丹参注射液可挽救糖尿病相关 ED,可能通过抑制氧化应激和内质网(ER)应激诱导的细胞凋亡途径。

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