Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model.
Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model.
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在啮齿动物糖尿病模型中用血管内皮生长因子基因修饰的脂肪干细胞纠正糖尿病勃起功能障碍
DOI：
10.1371/journal.pone.0072790
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Deng C
中科院分区：
文献类型：
--
作者：
Liu G;Sun X;Bian J;Wu R;Guan X;Ouyang B;Huang Y;Xiao H;Luo D;Atala A;Zhang Y;Deng C
本研究旨在探讨表达血管内皮生长因子（VEGF）基因的脂肪干细胞（ADSCs）能否改善糖尿病性勃起功能障碍（DED）大鼠模型的血管内皮功能，恢复受损的VEGF信号通路，并增加血管平滑肌含量。通过腹腔注射链脲佐菌素（40 mg/kg）诱导DED大鼠，然后用阿朴吗啡（100 µg/kg）筛选。使用五个组（n = 12/组）-组1（G1）：海绵体内注射慢病毒-VEGF; G2：ADSC注射; G3：VEGF表达的ADSC注射; G4：磷酸盐缓冲盐水注射; G1-G4是DED大鼠; G5：正常大鼠。 于注射后第7天和第28天测量平均动脉压（MAP）和海绵体内压（ICP）。对海绵窦组织中VEGF系统、内皮、平滑肌、周细胞标志物的组成进行了评估。注射后第28天，阴茎海绵体内注射表达VEGF的ADSC的组显示出比注射ADSC或慢病毒-VEGF的组更有效和显著地升高ICP和ICP/MAP（p<0.01）。免疫印迹和免疫荧光分析表明，ADSCs-VEGF改善的勃起功能与内皮标志物（VEGF、VEGF R1、VEGF R2、eNOS、CD 31和vWF）、平滑肌标志物（α-肌动蛋白和smoothelin）和周细胞标志物（CD 146和NG 2）的表达增加相关。表达VEGF的脂肪干细胞通过增强VEGF刺激的内皮功能和增加平滑肌和周细胞的含量产生治疗效果并恢复糖尿病大鼠的勃起功能。
The aim of this study was to determine whether adipose derived stem cells (ADSCs) expressing vascular endothelial growth factor (VEGF) gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED) model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then screened by apomorphine (100 µg/kg). Five groups were used (n = 12/group)–Group 1 (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1–G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2). ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.