氫水可治療糖尿病男性之性功能障礙(ED)研究

 
勃起功能障礙(ED)是男性性功能障礙的一種,指陰莖不能勃起或保持勃起狀態來完成性交活動,但可能會射精的症狀。ED產生原因有很多,而且大部分都可以進行治療。
 
在男性糖尿病患者中,ED的發生顯著高於健康男性。曾經有流行病學研究認為男性糖尿病患者超過50%存在不同程度的ED表現。磷酸二酯酶V型(PDE3)抑制劑(Viagra)通過NO-cGMP途徑鬆弛海綿體平滑肌促使陰莖勃起功能障礙,其改善勃起功能障礙功能達78%,安慰劑為20%,但會有頭暈、頭痛、潮紅、鼻堵、胃腸症狀、視力障礙等副作用;不能與NO製劑如硝酸甘油類合用。患有心臟病者應慎用。儘管使用磷酸二脂酶對許多ED有很好的治療效果。但對糖尿病合併ED的患者,Viagra的有效率明顯下降。因此,尋找針對糖尿病合患者ED的治療方法仍是學術界關注的重點問題。
 
最近來自中國蘇州大學第三附屬醫院泌尿科Fan Min等線上發表在泌尿學美國泌尿學會旗艦雜誌Journal of Urology》文章證明,給糖尿病動物飲用氫氣生理鹽水(5ml/kg/d),可以有效治療ED。這是在國際上首次關於氫氣可對ED具有治療效果的研究報導。

氫水的製備方法可透過1.電解,2.水與礦石反應、3.高壓灌注,選擇任一方法均可備製水中含氫之氫水,任一方法皆可並無特殊性、惟成本與時間之差異。日本、韓國、中國研究中使用之氫水,均因其實驗設計使用三種方式產生氫水,水中含氫氣即為氫水,檢測方法須應用溶氫檢測儀檢測之、只要水中含氫氣即為醫學研究所定義之氫水。

為什麼糖尿病患者ED發生率高,為什麼Viagra對糖尿病患者ED治療效果差的原因有許多研究,但真正的機制目前仍不十分清楚。許多研究發現,組織內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類組織的共同表現,也是導致糖尿病患者各類併發症的重要原因,使用抗氧化治療可以對部分糖尿病併發症有一定治療效果。超氧陰離子是氧氣分子不完全還原的最主要產物,當超氧陰離子遇到一氧化氮時,可以迅速變成毒性更強亞硝酸陰離子,同時導致一氧化氮的濃度下降,血管平滑肌擴張受到限制。另外,活性氧也可以導致陰莖組織發生細胞損傷甚至死亡。因此,抗氧化治療可能對糖尿病ED有一定作用。
 
氫氣被證明具有理想的抗氧化作用,在許多氧化損傷和炎症相關疾病中具有理想的治療效果。如氫氣可以治療腦、心臟、肝臟缺血再灌注損傷。Kajiyama等發現,給二型糖尿患者飲用氫水可以有效降低氧化損傷,提高葡萄糖代謝。從這個角度考慮,氫有可能對糖尿病引起的ED具有治療作用。


Fan Min等採用SD大鼠,通過腹腔注射STZ建立糖尿病模型。糖尿病動物分成兩組,治療組(8只)每天通過灌胃5ml/kg氫飽和生理鹽水,對照組給正常生理鹽水。連續治療8周後,博起功能通過檢測電刺激陰莖海綿體神經海綿竇內壓確定。分別檢測組織一氧化氮合酶活性、丙二醛含量、8羥基鳥嘌呤、亞硝酸鹽和硝酸鹽水平。一氧化氮合酶蛋白水準採用免疫組織化學檢測,一氧化氮合酶、Bcl-2Bax蛋白水準採用western blot檢測,一氧化氮合酶、Bcl-2Bax基因表達採用RT-PCR檢測。結果發現,氧化應激和ED病理生理學機制相關。和正常對照組相比,糖尿病動物海綿竇內壓顯著降低,經過氫治療後海綿竇內壓顯著升高。和對照組相比,糖尿病動物陰莖組織內NOS活性、NOxeNOS表達明顯降低,而8羥基鳥嘌呤、丙二醛含量明顯增加。經過氫治療後上述改變明顯恢復正常。海綿體細胞凋亡和相關蛋白基因表達和蛋白水平均符合上述改變。研究結果表明,氫對糖尿病動物的ED表現具有治療作用,該作用和氫的抗氧化減少細胞調亡提高eNOS功能有關。
 
 
 有意思的是,一氧化氮硫化氫已經被證明和男性性功能關係密切,現在的研究又證明也存在類似效應。從分子機制上考慮,氫的作用途徑並不清楚,但從應用前景考慮,氫和另外兩種氣體的作用方式完全不同。氫本身並不能直接發揮作用,而是依靠慢性長期(8周)作用。這需要引起注意。
 
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.
 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  Xuejun Sun, Department of Diving Medicine, Second Military Medical University, Shanghai 200433, China Accepted 3 December 2012 Available online 5 December 2012
 

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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