Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways
Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways
复制标题
小檗碱通过抑制 SPHK1/S1P/S1PR2 和 MAPK 通路减弱细胞凋亡，改善链脲佐菌素诱导的糖尿病大鼠的勃起功能障碍
DOI：
10.1111/andr.13119
复制
发表时间：
2021-10-27
期刊：
影响因子：
4.5
通讯作者：
Rao, Ke
中科院分区：
文献类型：
--
作者：
Liu, Kang;Sun, Taotao;Rao, Ke
背景糖尿病性勃起功能障碍的人群正在迅速增加，但目前的药物对治疗勃起功能障碍无效。研究中药提取物黄连素对糖尿病及其并发症的治疗为我们提供了新的思路。目的探讨黄连素对糖尿病大鼠勃起功能的影响及其可能机制。材料与方法雄性SD大鼠50只，随机分组，42只腹腔注射链脲佐菌素建立糖尿病模型。通过阿朴吗啡试验筛选出勃起功能障碍大鼠，随机分为糖尿病组和黄连素组，黄连素组给予黄连素200 mg/kg/d和生理盐水灌胃4周。原代培养健康大鼠阴茎海绵体平滑肌细胞，用小檗碱处理。结果糖尿病组空腹血糖明显升高，黄连素对血糖无明显影响。糖尿病组勃起功能明显受损，黄连素治疗可部分缓解这一损害。在糖尿病组中，鞘氨醇激酶1、S1 PR 2和鞘氨醇-1-磷酸的表达增加。小檗碱部分抑制鞘氨醇激酶1和S1 PR 2的表达，但鞘氨醇-1-磷酸的减少不显著。此外，在糖尿病组中，丝裂原活化蛋白激酶途径因子表达上调，eNOS活性降低。黄连素治疗可以部分逆转这些变化。糖尿病大鼠肝纤维化和细胞凋亡严重，TGF β 1、I/IV型胶原、Bax/Bcl-2和caspase 3的表达高于其他各组。然而，补充小檗碱抑制这些蛋白质的表达，并减弱纤维化和细胞凋亡。结论小檗碱可能通过抑制鞘氨醇激酶1/鞘氨醇-1-磷酸/S1 PR 2和丝裂原活化蛋白激酶通路，改善内皮功能，抑制细胞凋亡和纤维化，从而改善糖尿病大鼠勃起功能障碍。
Background The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. Objectives To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. Materials and methods Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. Results Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGF beta 1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. Conclusions Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.