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糖尿病大鼠阴茎组织中Mitofusin 2表达的改变

Altered expression of mitofusin 2 in penile tissues of diabetic rats.

作者信息

Yang J, Wang T, Zhang Y, Li R, Wang S, Xu H, Liu J, Ye Z

机构信息

Department of Urology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Andrologia. 2014 Jun;46(5):522-8. doi: 10.1111/and.12108. Epub 2013 May 19.

Abstract

Diabetic erectile dysfunction (ED) is a common complication in diabetes mellitus, and the efficacy of first-line therapies is not satisfactory. Recent studies revealed that corporal apoptosis was responsible for the nonresponsiveness of severe ED to phosphodiesterase type 5 inhibitors. Mitofusin 2 (Mfn2) is a versatile protein, regulating mitochondrial morphology and playing an important role in apoptosis. Several studies showed that expression of Mfn2 was decreased in STZ-induced diabetic rats' kidney, myocardium and retina, which was associated with diabetic nephropathy, cardiomyopathy and retinopathy respectively. In this study, our aim was to explore the expression of Mfn2 and apoptosis in diabetic rats' penes. We found that erectile function (ICP/MAP) elicited by electrical stimulation of cavernous nerve was markedly impaired in diabetic rats compared with the normal rats. The mRNA and protein levels of Mfn2 were found to be significantly reduced in diabetic rats' penile tissues. Compared with normal rats, the content of smooth muscle and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were dramatically decreased, and penile apoptotic index and expression of activated-caspase-3 were dramatically increased in diabetic rats. This data indicated that repression of Mfn2 in diabetic rats' penes might be associated with excessive apoptosis in diabetes-induced severe ED.

摘要

糖尿病性勃起功能障碍(ED)是糖尿病的常见并发症,一线治疗方法的疗效并不令人满意。最近的研究表明,海绵体凋亡是重度ED对5型磷酸二酯酶抑制剂无反应的原因。线粒体融合蛋白2(Mfn2)是一种多功能蛋白,可调节线粒体形态并在细胞凋亡中起重要作用。多项研究表明,链脲佐菌素诱导的糖尿病大鼠肾脏、心肌和视网膜中Mfn2的表达降低,分别与糖尿病肾病、心肌病和视网膜病变相关。在本研究中,我们的目的是探讨糖尿病大鼠阴茎中Mfn2的表达和细胞凋亡情况。我们发现,与正常大鼠相比,电刺激海绵体神经引起的糖尿病大鼠勃起功能(海绵体内压/平均动脉压)明显受损。糖尿病大鼠阴茎组织中Mfn2的mRNA和蛋白水平显著降低。与正常大鼠相比,糖尿病大鼠阴茎平滑肌含量及B细胞淋巴瘤-2(Bcl-2)/Bcl-2相关X蛋白(Bax)比值显著降低,阴茎凋亡指数及活化半胱天冬酶-3表达显著增加。该数据表明,糖尿病大鼠阴茎中Mfn2的抑制可能与糖尿病诱导的重度ED中过度的细胞凋亡有关。

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