四硫代钼酸盐通过影响铜蓝蛋白/内皮型一氧化氮合酶以及抑制阴茎海绵体纤维化和全身炎症，部分缓解1型糖尿病大鼠的勃起功能障碍。
Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation.
作者信息
Yin Yinghao, Peng Jingxuan, Zhou Jun, Chen Hanfei, Peng Dongyi, Li Dongjie, Gan Yu, Yin Guangming, Tang Yuxin
机构信息
Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China; Xiangya International Medical Center, Department of Geriatric Urology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, China.
出版信息
Sex Med. 2022 Feb;10(1):100455. doi: 10.1016/j.esxm.2021.100455. Epub 2021 Nov 21.
INTRODUCTION
Patients with erectile dysfunction induced by diabetes mellitus (DMED) show a poor effect rate for oral phosphodiesterase type 5 inhibitors (PDE5is). Therefore, the new therapeutic strategy is necessary in patients with DMED.
AIM
To investigate whether Tetrathiomolybdate (TM) supplementation could ameliorate DMED by activation of eNOS.
METHODS
Twenty-four diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and the other 6 normal rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with TM orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. After 1 week washout, the erectile function of rats in each group was evaluated. Then, the serum concentration of IL-6 and histologic changes of corpus cavernosum were measured.
MAIN OUTCOME MEASURE
Erectile function was measured after DMED rats treated with TM. The cavernosum level of Ceruloplasmin (Cp), eNOS, endothelial cell content, corporal fibrosis, apoptosis rate and the serum level of IL-6 were also assayed.
RESULTS
Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED+TM group. The DMED group showed upregulation of Cp and inhibition of eNOS, but the inhibition was partly reversed in the DMED+TM group. The DMED group showed serious corporal fibrosis. However, TM supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of apoptosis. What's more, gavage administration of TM profoundly decreased the serum level of IL-6 in DMED rats.
CONCLUSION
TM supplementation inhibits endothelial dysfunction, corporal fibrosis, and systemic inflammation, ultimately leading to partial improvement of DMED in rats. Yin Y, Peng J, Zhou J, et al., Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation. Sex Med 2022;10:100455.
引言
糖尿病性勃起功能障碍（DMED）患者口服5型磷酸二酯酶抑制剂（PDE5is）的有效率较低。因此，DMED患者需要新的治疗策略。
目的
研究补充四硫代钼酸盐（TM）是否能通过激活内皮型一氧化氮合酶（eNOS）改善DMED。
方法
通过腹腔注射链脲佐菌素（STZ）诱导24只糖尿病大鼠，另外6只正常大鼠作为对照组。8周后，用阿扑吗啡试验评估大鼠的勃起功能。仅对部分DMED大鼠每天口服TM治疗4周；其他大鼠保持相同状态4周。经过1周的洗脱期后，评估每组大鼠的勃起功能。然后，测量血清白细胞介素-6（IL-6）浓度和海绵体的组织学变化。
主要观察指标
用TM治疗DMED大鼠后测量勃起功能。还检测了海绵体中铜蓝蛋白（Cp）、eNOS水平、内皮细胞含量、海绵体纤维化、凋亡率以及血清IL-6水平。
结果
与对照组相比，DMED组的勃起功能明显受损，而DMED + TM组部分但显著改善。DMED组显示Cp上调和eNOS受抑制，但在DMED + TM组中这种抑制作用部分得到逆转。DMED组显示严重的海绵体纤维化。然而，补充TM部分增加了平滑肌与胶原的比例，降低了凋亡比例。此外，对DMED大鼠灌胃给予TM可显著降低血清IL-6水平。
结论
补充TM可抑制内皮功能障碍、海绵体纤维化和全身炎症，最终导致大鼠DMED部分改善。尹Y，彭J，周J等，四硫代钼酸盐通过影响铜蓝蛋白/eNOS并抑制海绵体纤维化和全身炎症部分缓解1型糖尿病大鼠的勃起功能障碍。性医学2022；10：100455。
Zotero 插件