Home 紅激光在醫學上的應用

紅激光在醫學上的應用

激光 / 鐳射線

激光 LASER 是 Light Amplification by Stimulated Emission of Radiation 的簡寫,是電磁波的一種,是物體的原子粒受外來能量刺激震動時,所產生的輻射,不同能量會產生不同的光譜。例如當原子粒個別隨機震動時,會產生能量較低的散發性光波,不能聚焦,最為人熟識的電磁波是可見光、及紅外線。
激光是屬於高能量光波,要求原子粒必須同步震動,才能釋放出頻率和波長相同的單色光波、它的光束狹窄、分散率低,並可以用透鏡來聚焦和操縱方向角度。 將激光的能量調高,可以用於外科手術切割或切除組織,能量調低時則可刺激生物組織的癒合和修復。

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LLLT – 紅激光療法

紅激光療法, 也被稱為低能量激光療法、光療、冷激光治療,光生物調整,生物刺激及光線療法,這些療法已在餘千的出版刊物、廣泛流傳、證明了光療能有效地增加細胞的存活,增殖和功能。

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紅激光療法在醫學上的應用

紅激光療法是最古老的治療方法之一, 遠在千百年前,古代埃及人己用太陽光治療疾病。在發明首部個激光儀器的數年後的1967年,一位匈牙利 塞梅爾魏斯恩大學 (Semmelweis University, Budapest, Hungary) 的學生,布達佩斯 Endre Mester,決定激光照射白老鼠,來研究測試激光會否引致致癌。他首先把白老鼠背部的毛剃掉,然後把他們分成兩組,其中一組用低能量的紅寶石激光 (波長694納米) 給牠們照射,另一組作對照。結果被激光照射的老鼠沒有患上癌病,反而背部的毛生長得還要被對照組快。 這就是第一個證明激光能刺激生物的實例。自那時起,光醫學治療漸漸發展萌芽,目前,紅激光或低能量激光治療 (也被稱為或光療、冷激光、軟激光、光生物刺激),己被公認為醫學療法或物理治療的一部份。

紅激光療法的光波可由兩種不同的儀器所產生:由激光二極管 Diodes 所產生的同步光波 coherent light 、和由 LED 所產生的非同步光波 noncoherent light ,以前者的聚焦力和功率較適合醫學上的應用。

自20世紀60年代,激光已被應用於加速傷口的癒合,其後有無數實驗室和臨床實驗,研究激光在醫學上的療法。1904年尼爾斯芬森 Nils Finsen 在光療上創新的開發,令他他獲得了諾貝爾獎。而激光二極管和 LED 的出現,更有助於光療技術進一步的發展,現時光療已成為全球成千上萬人每天生活的一部份。
近年來紅激光治療,更被廣泛地應用於治療遺傳性或後天脫髮。市面上已有激光梳、激光梳、座地激光罩等設備供禿髮患者使用。

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紅激光治療的臨床應用

紅激光或低能量激光治療 LLLT,已被被物理治療師用作治療各種急性和慢性肌肉骨骼酸痛;牙醫則用作治療口腔組織發炎和名種潰瘍。其他不同的專科醫生也存不同的使用方法,例如皮膚科醫生會用作治療浮腫,不癒合的潰瘍,燒傷和皮炎;風濕病學家用作止痛、治療慢性炎症和自身免疫性疾病等。在運動醫學與康復診所中,則用以減少腫脹和血腫,緩解疼痛,​​改善血液循環,治療急性軟組織損傷。光療也被廣泛應用在獸醫上,特別是在賽馬的馬匹培訓中心。

使用時將激光二極管或 LED,直接照射患處,例如,傷口或受傷的部位;或身體上的穴位及壓痛點等。而提供治療光波的方法是多種多樣的,通過光源的選擇(激光二極管或 LED),及調較輸出光波的不同參數 (波長、輸出功率、連續波或脈衝操作模式、脈衝參數、偏光狀態等),便能控制光譜的特徵,產生不同的使用方法和臨床用途。
在2002年,MicroLight Corp 公司所出產的 830-nm半導體激光二極管,獲美國藥物管理局 FDA 批準,用以治療腕管綜合症。此外,有多個對照試驗報告客觀地證實低能量激光,能顯著改善痛症。從那時起,低能量激光在治療廣泛性肌肉骨骼疾病的療效,已被公認相當於軟紅外線加熱燈。

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紅激光的先生物效應

紅激光的光波被細胞的線粒體 mitochondria 吸收後,會增加細胞呼吸,並通過活性氧的誘導,激活細胞核的轉錄因子的。臨床對照試驗顯示,在治療中風,促進傷口癒合,骨科疾病和慢性炎症等,有緩解功效。亦有效地而改善脊髓損傷,周圍性神經退化,心臟病,退化性腦部疾病、和創傷性腦損傷等。

現今科學家要面對的問題,已經不再是紅激光是否能產生光生物效應,而是該如何選擇光源,和調控最佳的光參數,來增加細胞能量和有機體的活動水平,達到最理想的治療效果。

光療醫学透過多項的細胞培養研究、動物實驗,及臨床研究,有一重要發現,證實光能量的密度(fluence)是一個雙相劑量反應 biphasic dose response。低能量的激光是最佳的光劑量,能產生最佳的醫療效應,當光劑量低於或大於這個最佳數值,會減少治療效果,甚至出現負面結果。

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紅激光與細胞生物學 (原文)

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The first law of photobiology states that for low power visible light to have any effect on a living biological system, the photons must be absorbed by electronic absorption bands belonging to some molecular chromophore or photoacceptor [4]. One approach to finding the identity of this chromophore is to carry out action spectra. This is a graph representing biological photoresponse as a function of wavelength, wave number, frequency, or photon energy and should resemble the absorption spectrum of the photoacceptor molecule. The existence of a structured action spectrum is strong evidence that the phenomenon under study is a photobiological one (i.e., cellular photoacceptors and signaling pathways exist).

The second important consideration involves the optical properties of tissue. Both the absorption and scattering of light in tissue are wavelength dependent (both much higher in the blue region of the spectrum than the red) and the principle tissue chromophores (hemoglobin and melanin) have high absorption bands at wavelengths shorter than 600-nm. Water begins to absorb significantly at wavelengths greater than 1150-nm. For these reasons there is a so-called “optical window” in tissue covering the red and near-infrared wavelengths, where the effective tissue penetration of light is maximized (Figure 1). Therefore although blue, green and yellow light may have significant effects on cells growing in optically transparent culture medium, the use of LLLT in animals and patients almost exclusively involves red and near-infrared light (600-950-nm).

It was suggested in 1989 that the mechanism of LLLT at the cellular level was based on the absorption of monochromatic visible and NIR radiation by components of the cellular respiratory chain [5]. Respiration occurs in subcellular organelles called mitochondria. The inner mitochondrial membrane contains 5 complexes of integral membrane proteins: NADH dehydrogenase (Complex I), succinate dehydrogenase (Complex II), cytochrome c reductase (Complex III), cytochrome c oxidase (Complex IV), ATP synthase (Complex V) and two freely-diffusible molecules ubiquinone and cytochrome c that shuttle electrons from one complex to the next. The respiratory chain accomplishes the stepwise transfer of electrons from NADH and FADH2 (produced in the citric acid or Krebs cycle) to oxygen molecules to form (with the aid of protons) water molecules harnessing the energy released by this transfer to the pumping of protons (H+) from the matrix to the intermembrane space. The gradient of protons formed across the inner membrane by this process of active transport forms a miniature battery. The protons can flow back down this gradient, reentering the matrix, only  through another complex of integral proteins in the inner membrane, the ATP synthase complex. In 1995, an analysis of five action spectra suggested that the primary photoacceptor for the red-NIR range in mammalian cells is cytochrome c oxidase [6] (Figure 2). It is remarkable that the action spectra that were analyzed had very close (within the confidence limits) peak positions in spite of the fact that these are seemingly different processes. The enzyme contains two iron centres, haem a and haem a3 (also referred to as cytochromes a and a3), and two copper centres, CuA and CuB [7]. Fully oxidized cytochrome c oxidase has both iron atoms in the Fe(III) oxidation state and both copper atoms in the Cu(II) oxidation state, while fully reduced cytochrome c oxidase has the iron in Fe(II) and copper in Cu(I) oxidation states. There are many intermediate mixed-valence forms of the enzyme and other coordinate ligands such as CO, CN, and formate can be involved. All the many individual oxidation states of the enzyme have different absorption spectra [8], thus probably accounting for slight differences in action spectra of LLLT that have been reported.

A recent paper from Karu’s group [9] gave the following wavelength ranges for four peaks in the LLLT action spectrum: 1) 613.5 – 623.5 nm, 2) 667.5 – 683.7 nm, 3) 750.7 – 772.3 nm, 4) 812.5 – 846.0 nm. Absorption of photons by molecules leads to electronically excited states and consequently can lead to acceleration of electron transfer reactions [10]. More electron transport necessarily leads to increased production of ATP [11]. Light induced increase in ATP synthesis and increased proton gradient leads to an increasing activity of the Na+/H+ and Ca2+/Na+ antiporters and of all the ATP driven carriers for ions, such as Na+/K+ ATPase and Ca2+ pumps. ATP is the substrate for adenyl cyclase, and therefore the ATP level controls the level of cAMP. Both Ca2+ and cAMP are very important second messengers. Ca2+ especially regulates almost every process in the human body (muscle contraction, blood coagulation, signal transfer in nerves, gene expression, etc.).

1. Singlet-Oxygen Hypothesis
In addition to cytochrome c oxidase mediated increase in ATP production, other mechanisms may be operating in LLLT. The first of these we will consider is the “singlet-oxygen hypothesis.” Certain molecules with visible absorption bands like porphyrins lacking transition metal coordination centers [12] and some flavoproteins [13] can be converted into a long-lived triplet state after photon absorption. This triplet state can interact with ground-state oxygen with energy transfer leading to production of a reactive species, singlet oxygen. This is the same molecule utilized in photodynamic therapy (PDT) to kill cancer cells, destroy blood vessels and kill microbes. Researchers in PDT have proposed that very low doses of PDT can cause cell proliferation and tissue stimulation instead of the killing observed at high doses.

2. Redox Properties Alteration Hypothesis
The next mechanism proposed was the “redox properties alteration hypothesis” [14]. Alteration of mitochondrial metabolism and activation of the respiratory chain by illumination would also increase production of superoxide anions O2 •-. It has been shown that the total cellular production of O2 •- depends primarily on the metabolic state of the mitochondria. Other redox chains in cells can also be activated by LLLT. In phagocytic cells irradiation initiates a nonmitochondrial respiratory burst (production of reactive oxygen species, especially superoxide anion) through activation of NADPHoxidase located in the plasma membrane of these cells [15]. The irradiation effects on phagocytic cells depend on the physiological status of the host organism as well as on radiation parameters.

It is now known that under physiological conditions the activity of cytochrome c oxidase is also regulated by nitric oxide (NO). This regulation occurs via reversible inhibition of mitochondrial respiration. It was hypothesized that laser irradiation and activation of electron flow in the molecule of cytochrome c oxidase could reverse the partial inhibition of the catalytic center by NO and in this way increase the respiration rate (“NO hypothesis”) [16]. Recent experimental results on the modification of irradiation effects with donors of NO do not exclude this hypothesis. Note also that under pathological conditions the concentration of NO is increased (mainly due to the activation of macrophages producing NO). This circumstance also increases the probability that the respiration activity of various cells will be inhibited by NO. Under these conditions, light activation of cell respiration may have a beneficial effect.

Several important regulation pathways are mediated through the cellular redox state. This may involve redox-sensitive transcription factors or cellular signaling homeostatic cascades from cytoplasm via cell membrane to nucleus. It is proposed that LLT produces a shift in overall cell redox potential in the direction of greater oxidation.

The overall redox state of a cell represents the net balance between stable and unstable reducing and oxidizing equivalents in dynamic equilibrium and is determined by three couples: NAD/NADH, NADP/NADPH, and GSH/GSSG (GSH = glutathione). It is believed now that extracellular stimuli elicit cellular responses such as proliferation, differentiation, and even apoptosis through the pathways of cellular signaling.

Modulation of the cellular redox state affects gene expression through cellular signaling (and induction of transcription factors. There are at least two well-defined transcription factors — nuclear factor kappa B (NF-kB) and activator protein (AP)-1 that have been identified as being regulated by the intracellular redox state [17-19].

As a rule, oxidants stimulate cellular signaling systems, and reductants generally suppress the upstream signaling cascades, resulting in suppression of transcription factors. It is believed now that redox-based regulation of gene expression appears to represent a fundamental mechanism in cell biology. It is important to emphasize that in spite of some similar or even identical steps in cellular signaling, the final cellular responses to irradiation can differ due to the existence of different modes of regulation of transcription factors. The magnitudes of the LLLT-effects are likely to be dependent on the initial redox status of a cell. The cellular response is weak or absent when the overall redox potential of a cell is optimal or near optimal for the particular growth conditions. The cellular response is stronger when the redox potential of the target cell is initially shifted to a more reduced state (and intracellular pH is lowered). This explains why the degrees of cellular responses can differ markedly in different experiments and why they are sometimes nonexistent.

2009 年荷蘭阿姆斯特丹第十七屆 ISHRS 周年科學研討會 DR. HAMBLIN 的發表