前 言

現代健身文化鼓勵人們追求多肌肉，少脂肪，追求輪廓分明的身體形态和線條，這意味着健康、強壯、力量、吸引力和人體美。

對于增肌的原理，大多數健身愛好者練了一輩子，增肌增了一輩子，都是稀裡糊塗的，很多健身博主/科普者也是一知半解。

聽他們講增肌的原理，一會“适應性增粗”，一會“撕裂後超量恢複”，一會“肌肉沒有辦法被迫生長”，讓人覺得捉急，因為這不包含任何信息量，跟沒說一樣。

要把原理講清楚，那就非常複雜了。關鍵詞：蛋白質合成、機械張力、細胞信号、DNA轉錄。

一、大多健身者對蛋白質存在誤解

大多說健身者都以為，我們吃下去的蛋白質作為原料，來構成我們的肌肉，這顯然不對，因為這混淆了“蛋白質”和“氨基酸”。我們構築身體，用的是氨基酸，不是蛋白質。

蛋白質由大量的氨基酸和鍵構成，是結構非常複雜的大分子物質[1]。我們舉兩個具有代表性的例子。第一個，人體血紅蛋白（圖2）。

第二個例子，某些真核生物體内的核糖體蛋白。

大家可以看出，蛋白質具有極其複雜的結構，我們根本不可能直接使用結構如此複雜的大分子物質來構建我們的身體，我們得先把蛋白質消化、拆分。

在消化和拆分的過程中，人利用各種胃蛋白酶，如胰蛋白酶[2][3][4][5]、腸蛋白酶[6][7][8][9]等，把食物中的蛋白質水解[10][11][12]成為最基本單位——氨基酸[13][14][15]、或多個氨基酸組成的短肽[16][17][18]，然後才能用它們用來構築我們的身體。

二、增肌，到底增是哪裡？

很多健身者都能回答：增的是肌纖維。

然後呢？沒了。

大多數人都知道“增粗肌纖維”、增加肌肉中的蛋白質合成，但肌纖維是如何變粗的，蛋白質合成到底在肌纖維的哪裡，卻說不清楚。

對于我們來說，首先要搞清楚肌纖維的結構，肌纖維中的蛋白質增到了哪裡。在一般人的認知中，細胞可能像個球一樣，圓圓的，中間是細胞核。

但肌細胞（肌細胞就是肌纖維）不是個球狀的構成，而是像長長的管子一樣。肌細胞表面是細胞膜，裡面主要有更多更細的“管子”：肌原纖維，它外面包裹着肌漿網，細胞裡還有線粒體、細胞核等等。

我們的肌肉之所以能夠收縮，主要是因為肌纖維内的肌原纖維，它的内部含有更多更細的“肌絲”：粗肌絲、細肌絲[5,6]。

肌肉收縮時，在神經系統釋放的生物電的刺激下[19][20][21][22]，粗細肌絲之間的“鎖”被打開[23][24][25][26][27]，ATP氧化釋放能量，帶動粗/細肌絲相互“滑行”，肌肉縮短，完成收縮[28][29]。

肌動蛋白[30][31][32]構成我們肌纖維中的細肌絲，肌球蛋白[33][34][35][36]構成粗肌絲。例如人心肌中的肌球蛋白複合物：

現在大家應該明白了，所謂增肌，主要增的是肌原纖維上的粗、細肌絲上的蛋白。

三、肌原纖維内的蛋白質是怎麼來的？

許多人簡單的認為，肌纖維中的蛋白質不就是吃下去的蛋白質分解成氨基酸組成的。這個說法沒錯，但幾乎就是廢話，因為氨基酸是如何組成蛋白質，這才是關鍵。

與大多數人想象的不同，實際上，蛋白質的種類非常多[37][38][39][40]。多到什麼程度呢？真核生物一個細胞内的蛋白質，就多達幾萬種。

蛋白質的結構非常複雜[41][42][43]，在空間中呈現立體的幾何形态[44][45]，具有多層的扭曲和折疊性狀[46][47][48][49][50]；隻要稍微有一點變化，它的功能、特性和穩定性就可能發生變化[51][52][53]。

蛋白質的結構非常複雜，當然也包括我們的肌肉。人肌肉裡的蛋白質是大量氨基酸構成的生物大分子物質[54][55][56][57]，人肌肉的肌球蛋白（及其結合物）在儀器的眼光下看上去長這樣。

由于人體肌肉中的蛋白質結構如此複雜，那麼很顯然，大量的氨基酸絕不可能憑白無故的、在沒有指引的前提下，就能按照某種預先設置好的方式來構建如此複雜的大分子蛋白質。

這就像你有大量的磚石，但是用磚石制造建築，需要設計圖，并不是把磚石胡亂堆在一起就是建築了。氨基酸組成蛋白質也是一樣的道理。毫無疑問，有什麼東西在引導它們。

答案是mRNA。

mRNA如同一條鍊子，上面預留了不同類型的氨基酸的結合區（密碼子）。身體把大量的氨基酸運輸過來，每個氨基酸可以對号入座，“組裝”到這條鍊子上。

當然，光是組裝還遠遠不夠。組裝好了以後，這隻是形成了蛋白質的雛形而已，蛋白質有四級空間結構，從宏觀上看，是多重折疊的。例如人體血紅蛋白，3D看是這樣：

但是，人體血紅蛋白，如果用圖形表示，在教科書上，是這樣的：

僅僅氨基酸“組裝”到mRNA上還不夠，還有折疊[58][59][60][61]、修飾[62][63][64][65]、轉運[66][67]等許多工作要做；我們把mRNA變成蛋白質（的雛形）這一步，叫做翻譯'[68][69][70][71][72]。

那mRNA哪來的呢？是DNA以它自身為模闆，複制出來的（單螺旋結構）。這一部叫做轉錄[73][74][75][76]；從DNA到蛋白質，宏觀上主要是轉錄和翻譯這兩步。

每種蛋白質都有對應的DNA。

如果我們把蛋白質視為産品，那麼DNA就是設計圖，蛋白質是依據DNA造出來的[77][78][79][80][81][82][83]。比如我們運輸氧氣的血紅蛋白[84][85]就是生物利用DNA編碼出來的[86]，人體内無窮多種的蛋白質、酶、身體結構，都是如此。

我們的每個細胞不斷凋亡，新的細胞不斷産生，這個産生過程，都是DNA表達的結果。我們也可以說，新陳代謝是依靠DNA來進行的，DNA是生命活動的中心。

四、訓練：刺激DNA表達

我們在前面說了，我們的肌肉中的蛋白質（肌動蛋白/肌球蛋白等）是大量氨基酸以特定方式排列組合而成的。氨基酸的排列組合，依靠mRNA；mRNA是DNA複制的産物。

所以，蛋白質的“制造”過程，最主要是兩部：DNA轉錄為mRNA，mRNA翻譯為蛋白質。

從DNA到蛋白質，這也叫基因的表達。

那為什麼DNA會開始轉錄？答案是，有什麼東西刺激了它。比如訓練，一種施加在肌纖維上的機械外力，也叫機械張力。張，顧名思義，把肌纖維往兩邊張開、拉開、扯開。

例如在啞鈴彎舉中，重力作用于啞鈴，啞鈴把肌纖維往下“扯”，我們自己的骨骼支撐，把肌纖維往上拉，則構成了一個往兩邊張開的力。

機械張力為什麼能刺激DNA表達[87][88][89]（轉錄）呢？因為我們有大量的生物感受器，能把外力信号，轉變為細胞内的生物信号，這些信号一直傳遞到DNA上，刺激了DNA的轉錄，于是我們得到了肌細胞内的蛋白質。

肌肉上能感知機械張力的生物傳感器有哪些呢？

例如肋節[90][91][92]，它将肌細胞膜與肌原纖維、細胞外基質連接起來，加強肌細胞膜的穩定性和強度，還能感受、偵測到施加于及細胞的外力（例如我們所說的機械張力），将其傳導到肌細胞内部，轉化為生物信号[16,17]；

71整合素[93][94]也是一種橫跨細胞膜的受體，它一方面提供連接作用[95]，一方面将機械信号從細胞外傳遞到細胞内。還有磷脂酸（PA）、FAK—粘着斑激酶等也參與機械張力轉化為細胞信号的傳導傳導，就不多說了。

五、訓練是如何刺激DNA表達的？答案是細胞信号

生物感受器将細胞信号傳遞到細胞内，引發一系列細胞信号事件。其中最著名、最核心的細胞信号事件，也被稱為PI3K/Akt/mTOR路徑[96][97][98][99][100]。還有一些别的相對次要的路徑（如ERK），礙于篇幅，我們就不在這裡說了。

mTOR是我們細胞内一種由2549個氨基酸組成的大型信号蛋白[101]——它既是蛋白質，也發揮信号作用。

mTOR全稱“哺乳動物雷帕黴素靶蛋白”，它是哺乳動物調節細胞生長、代謝、蛋白質合成等關鍵生理過程中的重要蛋白[102]。mTOR實際上以mTORC1（複合物1）和mTORC2（複合物2）的形式在人體内存在[103]。

MTORC1主要通過S6K1和eIF4E的磷酸化，來引發DNA表達，促進蛋白質合成[104]。此外，S6k1也提高mRNA的翻譯效率[105]。

對于健身者來說，最典型的激活mTORC1的因素，當然是訓練。

訓練刺激（機械張力）可激活mTORC1，使其磷酸化[106][107][108][109][110][111]；在mTOR的下遊，S6激酶[112][113][114]和eIF4E（真核生物起始因子4E）[115][116]随之也被磷酸化（紅色方框）。

磷酸化是自然界一種非常普遍的、對蛋白質進行化學修飾的過程[117]。

蛋白質磷酸化有效地增加了其複雜性，遠遠超過了基因組所賦予的多樣性[118]。

在磷酸激酶的作用下，生物将磷酸基團加在蛋白質或蛋白類中間産物上，從而将蛋白質磷酸化（或者去磷酸化）。經化學修飾後的蛋白質，功能/生物活性會顯著不同。

目前已知的磷酸激酶多大500多種，可針對超過20000種蛋白質上的25000個點位進行磷酸化[119][120][121][122]；磷酸化決定了在正常/病理狀态下生物體對刺激的反應[123]。

S6k1是DNA轉錄因子[124]，名至實歸。S6k1被激活後，接下來核糖體蛋白6被磷酸化，從而增加了核糖體蛋白與5'端寡核苷酸(5’-top)mRNA的親和力，引起了DNA轉錄[125][126][127]，增加蛋白質合成[128][129][130][131]。

反過來，如果蛋白質攝入不足，氨基酸/原料不夠，則可以導緻核糖體蛋白6的“去磷酸化”[132]。已知的誘導蛋白質去磷酸化的酶超過150種[119]。

研究發現，S6k它的磷酸化水平與增肌之間，存在極強的正相關性，r=0.998。下圖縱軸是肌肉增加的幅度，橫軸是s6k磷酸化水平，用俗話來說，它們幾乎成正比。

圖26：S6k磷酸化與增肌

六、能激活mTOR路徑的，不止有訓練

市面上有一種典型的錯誤觀點，認為訓練才能增肌，比如下面圖上的這種：

注意，圖中有2個錯誤：

錯誤1：認為增肌的原理是損傷修複。這個錯誤我們在前面已經解析過了，增肌的主要原理是DNA表達而不是損傷。民間認為損傷增肌，主要是因為損傷是來自于訓練，訓練能激發DNA表達。

錯誤2：認為訓練是增肌的前提。這也是錯的，除了訓練，營養[133][134][135][136][137][138][139][140][141]和激素[142][143][144][145][146]也都能激發DNA表達，因為他們的分子路徑是高度類似的，原理也相同：都是是通過刺激DNA的表達，來得到更多的肌蛋白。

當然，它們的效果程度不同，這或許是因為三者導緻的mTOR磷酸化程度不一樣。

我們肌肉中的蛋白質就是這麼來的：從激活細胞膜上的受體開始，一個個蛋白/酶依次被激活，最後激活DNA轉錄，然後mRNA翻譯為蛋白質。

許多人很難接受“隻打藥不練就可以長肌肉”，如果他們知道“隻吃蛋白粉不訓練也能長肌肉”，估計就更無法接受了。但這是客觀事實，不以他們的主觀意志為轉移。

Liu等人在《臨床内分泌與代謝雜志》上發表的了一項以10名健康年輕人為對象的研究，對他們注射氨基酸，觀察他們肌細胞内的變化（圖30），灰柱“AA”是注射氨基酸後，白色是注射前。縱軸是磷酸化水平。

氨基酸注射，導緻p70S6K和eIF4E磷酸化，進而增加了核糖體蛋白S6的磷酸化[147]。S6被磷酸化後，促進了一些在蛋白質合成中起重要作用的核糖體蛋白的合成[148][149]。

這些，也就證明了氨基酸注射或攝入能磷酸化4E-BP1、eIF4E、S6，進而引發蛋白合成：換句話說，單純的吃蛋白質不運動，也會多多少少長一些肌肉。

除了飲食/營養/訓練三者，我們還列舉了第四種刺激影響轉錄因子磷酸化的要素：光。

證據表明，光通過刺激SCN（視交叉上核），來影響ERK、或mTOR路徑的下遊因子S6核糖激酶的磷酸化[152]。具體的，在我們之前的文章中有過叙述。

https://www.zhihu.com/question/44055485/answer/1992536661

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