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首页> 外文期刊>BJU international >Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction.
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Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction.

机译：在患有勃起功能障碍的2型糖尿病大鼠模型中，动脉介质中纤维化的早期发作。

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OBJECTIVES: To determine, in the obese Zucker fa/fa rat (OZR), whether the loss in smooth muscle cells (SMCs) as well as the increase in fibrosis that occurs within the corpora cavernosa accompanying corporal veno-occlusive dysfunction (CVOD), also occurs within the media of the arterial tree. MATERIALS AND METHODS: The penis and aorta from both 7-month-old male diabetic OZR (5 months of diabetes) and aged-matched nondiabetic lean Zucker rats (LZR) rats were harvested (eight per group). The penis and aorta were subjected to histo- or immnohistochemistry, followed by quantitative image analysis (QIA) to determine the contents of SMC, collagen and the pro-fibrotic transforming growth factor (TGF)beta1. The turnover of SMCs was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) assays. Quantitative Western blots determined calponin (SMC marker) and PCNA, and hydroxyproline was used for collagen. In vitro relaxation of corporal strips was measured. RESULTS: In vitro relaxation of corporal tissue from OZR was considerably less than in the LZR. In the media of the penile dorsal artery (PDA) of OZR, there was a considerable reduction in the SMC content and the SMC/collagen ratio, as well as an increase in apoptosis, but there were no changes in PCNA or TGFbeta1 expression, or in the intima-media/lumen ratio. In the aorta of the OZR, in contrast to the PDA, there was a reduction in PCNA as well as a more pronounced decrease in the SMC/collagen ratio, mainly from an increase in collagen, but there were no changes in TGFbeta1 or the wall/lumen morphometry. In the OZR, Western blots of aortic tissue confirmed the decrease in PCNA and a reduction in the SMC marker calponin. CONCLUSIONS: These data show that 5 months after the onset of hyperglycaemia in the OZR, the rats develop both abnormal corporal SMC relaxation and a generalized fibrosis of the arterial media of both the large and small diameter vessels. It is possible that this pan-fibrosis of the media of the arterial system might contribute to the diabetes-related ED that occurs during this period in this rat model.
机译：目的：确定肥胖的Zucker fa / fa大鼠（OZR）中是否出现平滑肌细胞（SMCs）的损失以及海绵体伴随体静脉闭塞功能障碍（CVOD）发生的纤维化增加，也发生在动脉树的介质中。材料与方法：收集7个月大的男性糖尿病OZR（5个月糖尿病）和年龄匹配的非糖尿病瘦Zucker大鼠（LZR）大鼠的阴茎和主动脉（每组八只）。对阴茎和主动脉进行组织化学或免疫组化，然后进行定量图像分析（QIA），以确定SMC，胶原蛋白和促纤维化转化生长因子（TGF）β1的含量。通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）和增殖细胞核抗原（PCNA）分析评估SMC的转换。定量蛋白质印迹法测定了钙蛋白（SMC标记物）和PCNA，羟基脯氨酸用于胶原蛋白。测量了体外剥离体带。结果：OZR的体外组织松弛作用远小于LZR。在OZR的阴茎背动脉（PDA）的介质中，SMC含量和SMC /胶原蛋白比率显着降低，并且凋亡增加，但PCNA或TGFbeta1表达没有变化，或者内膜-中膜/管腔比率。在OZR的主动脉中，与PDA相比，PCNA降低，SMC /胶原蛋白比降低更明显，主要是由于胶原蛋白的增加，但TGFbeta1或壁没有变化/流明形态。在OZR中，主动脉组织的Western印迹证实了PCNA的减少和SMC标记钙蛋白的减少。结论：这些数据表明，在OZR高血糖症发作5个月后，大鼠出现了异常的SMC松弛以及大直径和小直径血管的动脉介质普遍纤维化。动脉系统介质的这种泛纤维化可能导致此大鼠模型在此期间发生的糖尿病相关性ED。

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