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氢气可治疗糖尿病男性性功能障碍

已有 9038 次阅读 2012-12-6 12:44 |个人分类:饮用氢气水|系统分类:论文交流| 糖尿病, 性功能障碍, 勃起功能

勃起功能障碍(ED)是男性性功能障碍的一种,指阴茎不能勃起或保持勃起状态来完成性交活动,但可能会射精的症状。ED产生原因有很多,而且大部分都可以进行治疗。在男性糖尿病患者中,ED的发生显著高于健康男性。曾经有流行病学研究认为男性糖尿病患者超过50%存在不同程度的ED表现。磷酸二酯酶V型(PDE3)抑制剂(Viagra)通过NO-cGMP途径松弛海绵体平滑肌促使阴茎勃起功能障碍,其改善勃起功能障碍功能达78%,安慰剂为20%,但会有头晕、头痛、潮红、鼻堵、胃肠症状、视力障碍等副作用;不能与NO制剂如硝酸甘油类合用。患有心脏病者应慎用。尽管使用磷酸二脂酶对许多ED有很好的治疗效果。但对糖尿病合并ED的患者,Viagra的有效率明显下降。因此,寻找针对糖尿病合患者ED的治疗方法仍是学术界关注的重点问题。

最近来自中国苏州大学第三附属医院泌尿科Fan Min等在线发表在泌尿学美国泌尿学会旗舰杂志《Journal of Urology》文章证明,给糖尿病动物饮用氢气生理盐水(5ml/kg/d),可以有效治疗ED。这是在国际上首次关于氢气可对ED具有治疗效果的研究报道。

为什么糖尿病患者ED发生率高,为什么Viagra对糖尿病患者ED治疗效果差的原因有许多研究,但真正的机制目前仍不十分清楚。许多研究发现,组织内活性氧大量增加可能是重要原因之一。活性氧大量增加是糖尿病患者各类组织的共同表现,也是导致糖尿病患者各类并发症的重要原因,使用抗氧化治疗可以对部分糖尿病并发症有一定治疗效果。超氧阴离子是氧气分子不完全还原的最主要产物,当超氧阴离子遇到一氧化氮时,可以迅速变成毒性更强亚硝酸阴离子,同时导致一氧化氮的浓度下降,血管平滑肌扩张受到限制。另外,活性氧也可以导致阴茎组织发生细胞损伤甚至死亡。因此,抗氧化治疗可能对糖尿病ED有一定作用。

氢气被证明具有理想的抗氧化作用,在许多氧化损伤和炎症相关疾病中具有理想的治疗效果。如氢气可以治疗脑、心脏、肝脏缺血再灌注损伤。Kajiyama等发现,给二型糖尿患者饮用氢水可以有效降低氧化损伤,提高葡萄糖代谢。从这个角度考虑,氢有可能对糖尿病引起的ED具有治疗作用。

Fan Min等采用SD大鼠,通过腹腔注射STZ建立糖尿病模型。糖尿病动物分成两组,治疗组(8只)每天通过灌胃5ml/kg氢饱和生理盐水,对照组给正常生理盐水。连续治疗8周后,博起功能通过检测电刺激阴茎海绵体神经海绵窦内压确定。分别检测组织一氧化氮合酶活性、丙二醛含量、8羟基鸟嘌呤、亚硝酸盐和硝酸盐水平。一氧化氮合酶蛋白水平采用免疫组织化学检测,一氧化氮合酶、Bcl-2Bax蛋白水平采用western blot检测,一氧化氮合酶、Bcl-2Bax基因表达采用RT-PCR检测。结果发现,氧化应激和ED病理生理学机制相关。和正常对照组相比,糖尿病动物海绵窦内压显著降低,经过氢治疗后海绵窦内压显著升高。和对照组相比,糖尿病动物阴茎组织内NOS活性、NOxeNOS表达明显降低,而8羟基鸟嘌呤、丙二醛含量明显增加。经过氢治疗后上述改变明显恢复正常。海绵体细胞凋亡和相关蛋白基因表达和蛋白水平均符合上述改变。研究结果表明,氢对糖尿病动物的ED表现具有治疗作用,该作用和氢的抗氧化减少细胞调亡提高eNOS功能有关。

 有意思的是,一氧化氮、硫化氢已经被证明和男性性功能关系密切,现在的研究又证明氢也存在类似效应。从分子机制上考虑,氢的作用途径并不清楚,但从应用前景考虑,氢和另外两种气体的作用方式完全不同。氢本身并不能直接发挥作用,而是依靠慢性长期(8周)作用。这需要引起注意。

 

Protective Effects of Hydrogen-rich Saline against Erectile Dysfunction in a Streptozotocin-Induced Diabetic Rat Model
  • 1 Department of Urology, the Third Affiliated Hospital of Soochow University, Changzhou 213000, Jiangsu Province, China
  • 2 Department of Haematology , Navy General Hospital, Beijing, 100048,China
  • 3 Department of Diving Medicine, Second Military Medical University, Shanghai 200433,China.
Corresponding author contact information Correspondence: Xiaozhou He, Department of Urology, the Third Affiliated Hospital of Soochow University, Jiangsu Changzhou 213003, China, Tel: (086)519 68871251, Fax: (086)519 86621235 Corresponding author contact information Xuejun Sun, Department of Diving Medicine, Second Military Medical University, Shanghai 200433, China Accepted 3 December 2012 Available online 5 December 2012

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Abstract Objective

Hydrogen has anti-oxidative-stress and anti-inflammatory effects. In the present study, we investigated the effect of hydrogen on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Rats with diabetes mellitus (DM) in the hydrogen-rich saline (HRS) group were fed saturated hydrogen saline by intragastric administration (5 ml/kg/d) for 8 weeks (n = 8).

Materials and Methods

Diabetes was induced in Sprague–Dawley rats by a single intravenous injection of STZ. The diabetic rats were then randomized into a DM group and a DM hydrogen saline group; the latter were fed saturated hydrogen saline by intragastric administration (5 ml/kg/d) for 8 weeks (n = 8). At the end of week 8, erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Nitric oxide synthase (NOS) activity, malondialdehyde (MDA) content, 8-hydroxydeoxyguanosine (8-OhdG), and nitrite and nitrate (NOx) levels were measured in corpus cavernosum tissues. Immunolocalization of the endothelial NO synthase (eNOS) protein in corpus cavernosum tissues was detected using immunohistochemistry. Protein expression of eNOS, Bcl-2, and Bax was determined by Western blotting. eNOS, Bcl-2, and Bax mRNA levels were determined using real-time reverse transcription polymerase chain reaction methods.

Results

Oxidative stress is involved in the pathophysiological mechanism of ED. Maximum ICP in diabetic rats decreased significantly compared to that in controls. Maximum ICP increased significantly compared to that in untreated diabetic rats after treatment with HRS. Decreased levels of NOS activity, NOx and eNOS expression, as well as elevated levels of 8-OhdG and MDA were found in the DM group compared with those in the control group. HRS treatment improved NOS activity and MDA, NOx, and 8-OHdG levels in the corpus cavernosum of diabetic rats. Decreased eNOS expression in diabetic rats was ameliorated by HRS treatment. In addition, apoptosis in the diabetic rat corpus cavernosum was enhanced significantly compared with that in the control group. HRS therapy may reduce apoptosis in corpus cavernosum tissues. Furthermore, HRS ameliorated ED in diabetic rats by inhibiting oxidative stress and apoptosis.

Conclusions

HRS treatment effectively improved erectile function in a STZ-induced diabetic rat ED model.



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