Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Sex Med. 2020 Aug;17(8):1434-1447. doi: 10.1016/j.jsxm.2020.04.390. Epub 2020 Jun 23.
Management of diabetes mellitus induced-erectile dysfunction (DMED) is challenging because of its poor responses to phosphodiesterase type 5 inhibitors. Increasingly important roles of 12-lipoxygenase (12-LOX) have been proven in diabetes mellitus.
To investigate 12-LOX activity and therapeutic effect of its inhibitor, baicalein (BE), on DMED.
Intraperitoneal streptozotocin injection was used to induce type I DM, and an apomorphine test was used to evaluate erectile function. In experiment A, we assessed 12-LOX expression alteration in the corpus cavernosum (CC) of rats with DMED of different levels of severity. In experiment B, rats with DMED were intraperitoneally injected with BE for 4 weeks, and control rats were injected with vehicles. The erectile function was tested by cavernous nerve stimulation before penile tissue was harvested. We performed Western blot, immunohistochemistry, immunofluorescence, Masson trichrome staining, and enzyme-linked immunosorbent assays to measure related proteins in CC.
The main outcome measures included rectile response, histologic examination, and expression alteration of related proteins.
12-LOX upregulation was associated with the progression of type I DMED. After 4 weeks treatment, compared with the DMED group, the DMED + BE group showed better erectile responses to cavernous nerve stimulation. In the DMED + BE group, significantly enhanced endothelial nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate pathway, reduced 12-LOX expression, and inhibited p38 mitogen-activated protein kinase/arginase II/L-arginine pathway were showed in CC relative to the DMED group. In addition, overactivated oxidative stress and fibrosis in the DMED group were both partially ameliorated in the DMED + BE group.
BE may be considered as an effective therapy for DMED, but needs to be verified in future human investigations.
STRENGTHS & LIMITATIONS: The role of 12-LOX and its inhibitor, BE, is firstly demonstrated in rats with type I DMED. However, the experimental data are derived from animal models with without evidences from cellular-based experiments.
12-LOX might serve as an important factor in the pathogenesis of type I DMED. BE alleviated erectile dysfunction in rats with type I DMED probably by inhibiting 12-LOX expression, ameliorating endothelial nitric oxide synthase dysfunction, as well as suppressing oxidative stress and fibrosis. Chen Y, Zhou B, Yu Z, et al. Baicalein Alleviates Erectile Dysfunction Associated With Streptozotocin-Induced Type I Diabetes by Ameliorating Endothelial Nitric Oxide Synthase Dysfunction, Inhibiting Oxidative Stress and Fibrosis. J Sex Med 2020;17:1434-1447.
由于磷酸二酯酶 5 抑制剂对糖尿病引起的勃起功能障碍（DMED）的反应不佳，因此对其进行管理具有挑战性。12-脂氧合酶（12-LOX）的作用越来越重要，已在糖尿病中得到证实。
研究 12-LOX 活性及其抑制剂黄芩素（BE）对 DMED 的治疗作用。
腹腔内注射链脲佐菌素诱导 I 型糖尿病，并用阿朴吗啡试验评估勃起功能。在实验 A 中，我们评估了不同严重程度 DMED 大鼠海绵体（CC）中 12-LOX 表达的改变。在实验 B 中，DMED 大鼠腹腔内注射 BE 治疗 4 周，对照组大鼠注射载体。在采集阴茎组织之前，通过海绵体神经刺激测试勃起功能。我们进行 Western blot、免疫组织化学、免疫荧光、Masson 三色染色和酶联免疫吸附测定，以测量 CC 中的相关蛋白。
主要观察指标包括勃起反应、组织学检查和相关蛋白的表达改变。
12-LOX 的上调与 I 型 DMED 的进展有关。经过 4 周的治疗，与 DMED 组相比，DMED+BE 组对海绵体神经刺激的勃起反应更好。与 DMED 组相比，DMED+BE 组的内皮型一氧化氮合酶/一氧化氮/环鸟苷 monophosphate 通路明显增强，12-LOX 表达降低，p38 丝裂原活化蛋白激酶/精氨酸酶 II/L-精氨酸通路受到抑制。此外，DMED 组过度激活的氧化应激和纤维化在 DMED+BE 组中部分得到改善。
BE 可被视为治疗 DMED 的有效方法，但需要在未来的人类研究中进一步验证。
12-LOX 及其抑制剂 BE 在 I 型 DMED 大鼠中的作用首次得到证实。然而，实验数据来自于没有细胞水平实验证据的动物模型。
12-LOX 可能是 I 型 DMED 发病机制中的一个重要因素。BE 可能通过抑制 12-LOX 表达、改善内皮型一氧化氮合酶功能障碍以及抑制氧化应激和纤维化来减轻 I 型 DMED 大鼠的勃起功能障碍。Chen Y, Zhou B, Yu Z, et al. Baicalein Alleviates Erectile Dysfunction Associated With Streptozotocin-Induced Type I Diabetes by Ameliorating Endothelial Nitric Oxide Synthase Dysfunction, Inhibiting Oxidative Stress and Fibrosis. J Sex Med 2020;17:1434-1447.
