以氫氧產生器應用於 COPD 疾病模型之治療

Abstract

本研究目的是探討氫氧產生器在慢性阻塞性肺病 (Chronic obstructive pulmonary disease; COPD) 動物模型中的應用機制，並進一步探究其對 COPD 治療的潛力。COPD 是一種常見的呼吸系統疾病，目前最常見的治療方式不外乎是氣體治療 (氧氣) 與藥物治療 (類固醇) 等，但這些都只能暫緩此病症，因此研究者希冀能找尋一種新型的治療方法來減緩或是降低 COPD 的症狀。氫氧治療在既往文獻中已經被證明對身體多個器官如肝臟、腎臟、肺臟等，具備抗發炎的治療效果。因此，本研究擬使用能穩定提供富含氧氣和氫氣的氫氧產生器 (Hydrogen-Oxygen generator) 來治療 COPD。此種治療方式具有以下特點：(1) 氫氣具有抗氧化、抗發炎的效果；(2) 氫氧產生器為非藥物型的治療，可有效的降低對藥物的依賴性，也降低藥物潛在的副作用或是相互作用 (如常見的類固醇治療)、亦可以降低藥物治療的醫療成本；(3) 氫氧產生器更可提供額外的氫氣與氧氣，可以有效減緩呼吸困難。而在實驗過程中，我們首先建立了大鼠的香菸煙霧模型以模擬 COPD 患者，接著我們進一步評估 COPD 大鼠在接受氫氧產生器治療後的各種生理現象和生化指標，以驗證其對 COPD 治療的效果。 研究結果可知：在大鼠的香菸煙霧模型中，發現：(1) 大鼠暴露在香菸煙霧中的第二周開始，大鼠的體重之間就出現顯著的差異性。控制組 (未吸菸組) 的體重在第一個月、第二個月、第三個月相較於吸菸組重 25%, 24%, 26%；(2) 在支氣管肺泡灌洗液 (Bronchoalveolar lavage fluids; BALF) 中，大鼠在經過香菸煙霧處理三個月後，其總白血球數量、嗜中性球、淋巴球、單核球則分別增加了 1.71, 1.26, 4.11, 2.1 倍；(3) 大鼠在經過香菸煙霧處理三個月後，其三尖瓣環收縮期偏移 (Tricuspid annular systolic excursion; TAPSE) 數值在第二個月、第三個月相較於第一個月分別下降了 67.1%、42.8%。 另一方面，受到香菸煙霧損傷後的大鼠，再進一步給予氫氧產生器的治療後顯示：(1) 在總白血球數值中，給予氫氧產生器的治療之數值僅有吸菸損傷後自然恢復的 0.83 倍，但是給予類固醇的治療反而增加 2 倍；而控制組 (未吸菸組) 再額外給予類固醇後的總白血球數值相較於單純的控制組反而增加了 1.88倍；(2) 在嗜中性球數值中，給予氫氧產生器的治療之數值僅有吸菸損傷後自然恢復的 0.74 倍，但是給予類固醇的治療反而增加 3.48 倍； (3) 在平均線性截距 (Mean linear intercept; MLI) 數值中，給予氫氧產生器的治療之數值下降至僅有吸菸損傷後自然恢復的 0.53 倍；(4) 在肺泡密度的平均值 (Mean value of alveolar density; MAN) 數值中，給予氫氧產生器的治療相較於吸菸損傷後自然恢復的情形增加 1.2 倍； (5) 在三尖瓣環收縮期偏移 (TAPSE) 數值中，給予氫氧產生器的治療之數值上升至僅有吸菸損傷後自然恢復的 1.08 倍。 根據以上結果，我們可以成功地建立一套大鼠的香菸煙霧模型、且肺部受損的大鼠在給予氫氧產生器治療後的效果明顯優於類固醇。除此之外，氫氧產生器可通過水電解的方式，產出我們需要的氫氣與氧氣 (流速、濃度、比例都可依情況調控)，這種方式不但簡便也更為環保。相信這樣的技術能給予 COPD 患者一個新的臨床治療策略、也期待其對於推進相關學科領域的研究發展具有重要的意義。

The objective of this study is to investigate the application mechanism of a hydrogen-oxygen generator in a chronic obstructive pulmonary disease (COPD) animal model and explore its potential for COPD treatment. COPD is a common respiratory disease, and the current standard treatments involve gas therapy (oxygen) and medication (steroids), which only provide temporary relief. Therefore, researchers aim to find a novel treatment method to alleviate or reduce COPD symptoms. Hydrogen therapy has been proven in previous literature to have anti-inflammatory effects on various organs, including the liver, kidneys, and lungs. In this study, a hydrogen-oxygen generator, capable of stably providing oxygen and hydrogen, will be used for COPD treatment. This treatment approach has the following characteristics: (1) Hydrogen has antioxidant and anti-inflammatory effects. (2) The hydrogen-oxygen generator provides a non-pharmacological treatment, effectively reducing dependence on medication, lowering potential side effects or interactions associated with drugs (such as common steroid treatments), and decreasing medical costs. (3) The generator can supply additional hydrogen and oxygen, effectively alleviating respiratory difficulties. In the experimental process, we first established a cigarette smoke model in rats to simulate COPD patients. Subsequently, we evaluated various physiological and biochemical indicators in COPD rats after receiving treatment with the hydrogen-oxygen generator to validate its effectiveness in COPD treatment. The research findings indicate that in the rat model exposed to cigarette smoke: (1) From the second week of exposure to cigarette smoke, significant differences in body weight among rats were observed. The control group (non-smoking group) showed a weight gain of 25%, 24%, and 26% compared to the smoking group in the first, second, and third months, respectively. (2) In the Bronchoalveolar Lavage Fluid (BALF), after three months of exposure to cigarette smoke, rats exhibited a respective increase of 1.71-fold, 1.26-fold, 4.11-fold, and 2.1-fold in total white blood cell count, neutrophils, lymphocytes, and monocytes. (3) Tricuspid annular systolic excursion (TAPSE) values decreased by 67.1% and 42.8% in the second and third months, respectively, after three months of cigarette smoke treatment compared to the first month. On the other hand, in rats damaged by cigarette smoke and subsequently treated with a hydrogen-oxygen generator: (1) The treatment with the hydrogen-oxygen generator resulted in a total white blood cell count only 0.83-fold of the natural recovery after smoking damage. In contrast, steroid treatment increased it by 2-fold. Additional steroid treatment in the control group (non-smoking group) increased the total white blood cell count by 1.88-fold compared to the control group without treatment. (2) The neutrophil count with hydrogen-oxygen generator treatment was only 0.74-fold of the natural recovery after smoking damage, while steroid treatment increased it by 3.48-fold. (3) The Mean Linear Intercept (MLI) with hydrogen-oxygen generator treatment was reduced it by 0.53-fold of the natural recovery after smoking damage. (4) The Mean Value of Alveolar Density (MAN) with hydrogen-oxygen generator treatment increased by 1.2-fold compared to the natural recovery after smoking damage. (5) In the tricuspid annular systolic excursion (TAPSE) values, treatment with a hydroxyl generator increased the value to 1.08 times that of spontaneous recovery after smoking injury only. Based on the above results, we have successfully established a rat model exposed to cigarette smoke, and the therapeutic effects of a hydrogen-oxygen generator on rats with lung damage are significantly superior to steroids. In addition, the hydrogen-oxygen generator can produce the required hydrogen and oxygen through water electrolysis, with the flow rate, concentration, and ratio adjustable as needed. This method is not only convenient but also more environmentally friendly. We believe that such technology can provide a new clinical treatment strategy for COPD patients and anticipate its significant impact on advancing research development in related disciplines.