Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats.
Decreased expression of pigment epithelium-derived factor within the penile tissues contributes to erectile dysfunction in diabetic rats.
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DOI：
10.1042/cs20180192
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发表时间：
2018-10
期刊：
影响因子：
6
通讯作者：
Hongjie Qiao;Yuanyuan Zhang;Wenwen Lin;Yu-Feng Wang;C. Furdui;Qiuling Jiang;Xiao Li;Ting Long;Yunguang Wang;D. Qin
中科院分区：
文献类型：
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作者：
Hongjie Qiao;Yuanyuan Zhang;Wenwen Lin;Yu-Feng Wang;C. Furdui;Qiuling Jiang;Xiao Li;Ting Long;Yunguang Wang;D. Qin
活性氧（ROS）和炎症的产生增加是糖尿病相关性勃起功能障碍（DMED）发展和进展的主要因素。色素上皮衍生因子（PEDF）作为一种内源性抗氧化和抗炎因子，在DMED中的潜在意义尚未被揭示。为了评估PEDF在DMED中潜在的抗氧化和抗炎功能，我们首先证明，与正常对照组相比，糖尿病大鼠阴茎中PEDF在mRNA和蛋白水平上显著降低。为了检验PEDF的阴茎水平降低与DMED中的氧化应激和炎症相关的假设，在糖尿病发作后2周，在阴茎海绵体内施用表达PEDF的腺病毒（Ad-PEDF）或相同滴度的对照病毒（Ad-GFP）。治疗6周后，我们发现Ad-PEDF可通过恢复正常大鼠的内皮型一氧化氮合酶（eNOS）、P-eNOS和神经型一氧化氮合酶（nNOS）蛋白水平，抑制肿瘤坏死因子-α（TNF-α）和氧化应激水平，显著增加糖尿病大鼠对海绵体神经刺激的勃起反应。总之，目前的数据表明，PEDF的抗氧化和抗炎潜力通过抑制氧化应激和TNF-α的产生在恢复勃起功能中发挥重要作用。
Increased production of reactive oxygen species (ROS) and inflammation are major contributors to the development and progression of diabetes-associated erectile dysfunction (DMED). As an endogenous antioxidant and anti-inflammatory factor, the potential implication of pigment epithelium-derived factor (PEDF) in DMED has not been revealed. To assess the potential antioxidant and anti-inflammatory functions of PEDF in DMED, we first demonstrated that PEDF was significantly decreased at the levels of the mRNA and protein in the penis of diabetic rats compared with normal controls. To test the hypothesis that decreased the penile levels of PEDF are associated with oxidative stress and inflammation in DMED, an adenovirus expressing PEDF (Ad-PEDF) or the same titer of control virus (Ad-GFP) was intracavernously administered at 2 weeks after diabetic onset. After 6 weeks of treatment, we found that administration of Ad-PEDF could significantly increase erectile response to cavernosal nerve stimulation in the diabetic rats by restoring the endothelial NO synthase (eNOS), P-eNOS, and neuronal NO synthase (nNOS) protein levels to the standard levels represented in normal rats and by suppressing the levels of tumor necrosis factor-α (TNF-α) and oxidative stress. In conclusion, the present data indicated that the antioxidant and anti-inflammatory potential of PEDF plays important role in restoring erectile function by the inhibition of oxidative stress and TNF-α production.