漆偉 雷偉 嚴(yán)亞波 張揚(yáng) 劉帥 曹鵬沖 樊勇
·綜述·
冬蟲夏草藥理學(xué)作用的研究進(jìn)展
漆偉 雷偉 嚴(yán)亞波 張揚(yáng) 劉帥 曹鵬沖 樊勇
冬蟲夏草是中國(guó)的一種傳統(tǒng)名貴中藥,富含了蟲草多糖、蟲草素、蟲草酸、蟲草多肽、麥角甾醇等多種單體活性成分?,F(xiàn)代醫(yī)學(xué)發(fā)現(xiàn)其具有抗腫瘤、免疫調(diào)節(jié)、降血糖、抗氧化、對(duì)腎臟的保護(hù)作用等廣泛的藥理學(xué)功能。目前的研究已證實(shí)冬蟲夏草及其單體活性成分可以有效的治療多種疾病。本文在檢索近幾年來有關(guān)冬蟲夏草及單體活性成分藥理作用的相關(guān)研究資料的基礎(chǔ)上,主要從冬蟲夏草的單體活性成分的研究現(xiàn)狀及冬蟲夏草的藥理學(xué)作用的研究進(jìn)展兩個(gè)方面對(duì)目前冬蟲夏草及單體活性成分藥理作用進(jìn)行歸納和總結(jié),為今后進(jìn)一步開發(fā)和利用冬蟲夏草提供幫助。
冬蟲夏草; 單體活性成分; 藥理學(xué)作用
冬蟲夏草Cordycepssinensis是寄生在蝙蝠蛾科昆蟲幼蟲上的一種麥角菌科真菌,后與幼蟲尸體結(jié)合形成的復(fù)合體,“蟲”是蟲草蝙蝠蛾的幼蟲,“菌”是蟲草真菌。早在1757年,清代的醫(yī)學(xué)家吳儀洛在其所著的《本草從新》中就對(duì)冬蟲夏草有過詳細(xì)的描述,指出其具有保肺、益腎、止血、祛痰、止喘之功效。后來,清代的另外一名學(xué)者趙學(xué)敏在《本草綱目拾遺》中也對(duì)冬蟲夏草進(jìn)行過記載,稱其“味甘性溫,益氣秘精,專補(bǔ)命門,功同人參”。而國(guó)外學(xué)者對(duì)冬蟲夏草的研究最早始于1947年,Mains教授首次分析并驗(yàn)證了冬蟲夏草相關(guān)成分及藥理學(xué)作用[1]。之后幾十年里,隨著現(xiàn)代生物技術(shù)的飛速發(fā)展,全世界對(duì)冬蟲夏草的關(guān)注程度逐漸加大,對(duì)其藥理學(xué)性質(zhì)及作用研究更是日新月異。本文將近年來國(guó)內(nèi)外對(duì)冬蟲夏草藥理學(xué)的相關(guān)研究進(jìn)行綜述,為后來學(xué)者的研究提供參考依據(jù)。
不同的學(xué)者采用不同的方法對(duì)冬蟲夏草及其菌絲體的化學(xué)成分進(jìn)行了廣泛的研究,其化學(xué)成分大致可分為多糖類、蛋白質(zhì)及氨基酸類、脂類、核苷類、甘露醇、麥角甾醇類、微量元素等。
在眾多活性成分中,目前研究最多、藥理學(xué)功效最為顯著的有蟲草多糖、蟲草素、蟲草酸以及蟲草多肽,這些單體成分已經(jīng)被證實(shí)在抗腫瘤、抗炎、抗菌、抗氧化、降血糖等多個(gè)方面具有顯著的效果,這為臨床應(yīng)用提供了新的方向。
1.1 蟲草多糖(Cordyceps Polysaccharide)
冬蟲夏草含有大量的多糖類物質(zhì),稱之為蟲草多糖,是冬蟲夏草中占比重最大的成分。這些醛糖和(或)酮糖通過糖苷鍵連接在一起的多聚物可以占到蟲草干重的20%~35%,其主要來源于菌絲體的分泌[2]?,F(xiàn)有研究證實(shí),蟲草多糖具有多種生物學(xué)活性, 包括抗腫瘤[3]、抗氧化[4]、免疫調(diào)節(jié)[5-6]、增強(qiáng)單核巨噬細(xì)胞的吞噬能力[7-8]和抗纖維化作用[9]等。特別是抗腫瘤作用尤為明顯。動(dòng)物實(shí)驗(yàn)證實(shí),從大團(tuán)囊蟲草中分離出來的蛋白結(jié)合多聚糖可以顯著的抑制大鼠肉瘤S-180的生長(zhǎng)[10]。但是,蟲草多糖并不僅僅是一種多聚糖,而是冬蟲夏草中許多分子量大小不同,結(jié)構(gòu)迥異的多糖的統(tǒng)稱,Sasaki等[11]研究表明,真菌多糖抗腫瘤活性與分子量有關(guān),只有分子量大于16000 g/mol時(shí)才具有抗腫瘤活性。因此,目前很多學(xué)者都在積極研究從蟲草中分離出具有較高活性的蟲草多糖組分,從而更加有效運(yùn)用于臨床治療。另外,蟲草多糖還可以降低糖尿病動(dòng)物的血糖水平,并升高血清胰島素水平,其機(jī)制是可能通過刺激胰島素釋放和(或)減少胰島素代謝來降低血糖水平[12]。
1.2 蟲草素(Cordycepin)
1951年,Cunningham等[13]首次從蛹蟲草中分離得到一種化學(xué)結(jié)構(gòu)為3’-脫氧腺苷的核苷類物質(zhì),也就是蟲草素。蟲草素在體內(nèi)代謝大部分遵循嘌呤核苷酸代謝途徑,在腺苷脫氨酶(ADA)作用下快速脫氨基而成為無生物活性的代謝產(chǎn)物3’-脫氧次黃嘌呤核苷,小部分磷酸化為三磷酸蟲草素。隨著研究的深入,人們對(duì)蟲草素的生物活性的認(rèn)識(shí)不斷清晰。蟲草素本身就是核苷類物質(zhì),因此可以滲透入腫瘤的DNA或者RNA中發(fā)揮作用。Ioannidis等[14]研究發(fā)現(xiàn),蟲草素能夠顯著抑制多聚A核酸聚合酶的活性,干擾mRNA的形成,繼而影響蛋白質(zhì)的合成。也有研究報(bào)道稱蟲草素可提高JNK蛋白激酶以及p38激酶活性,增加Bcl-2家族蛋白的表達(dá),抑制膀胱癌細(xì)胞,結(jié)腸癌細(xì)胞增殖,誘導(dǎo)其凋亡[15]。另有學(xué)者發(fā)現(xiàn),蟲草素可激活糖原合成酶激酶p38和抑制細(xì)胞周期蛋白D1來激活腫瘤細(xì)胞中腺嘌呤核苷A3受體產(chǎn)生,抑制小鼠黑色素瘤B16-BL6細(xì)胞和Lewis肺癌細(xì)胞的增殖[16-17]。值得注意的是,蟲草素還具有廣譜抗菌的作用,它既能抑制多種細(xì)菌的滋生,還能顯著抑制真菌的生長(zhǎng)[18-19]。另外,蟲草素還具有強(qiáng)大的抗病毒作用,研究發(fā)現(xiàn),蟲草素可以抑制皰疹病毒Dejulian-Ortiz活性,對(duì)抗莫洛尼鼠白血病病毒,對(duì)人體免疫缺陷病毒HIV-I型的侵入及其反轉(zhuǎn)錄酶的活性具有顯著的抑制作用[20-22]。除此之外,蟲草素還具有抗炎[23-24]、降血糖[25]、降脂[26-27]等多種藥理學(xué)作用。
1.3 蟲草酸(Cordycepic acid)
蟲草酸是由Chatterjee等人在1957年首次從冬蟲夏草中提取出來并命名,其化學(xué)結(jié)構(gòu)為 1,3,4,5-四羥基環(huán)已酸[28],后被證實(shí)為D-甘露醇。張小強(qiáng)等[29]通過實(shí)驗(yàn)發(fā)現(xiàn),蟲草酸對(duì)于羥自由基(Hydroxy free radical,HFR)可以有效的清除,可以推測(cè)D-甘露醇是蟲草中對(duì) HFR具有清除作用的主要的有效組分。另外,有研究表明,蟲草素可以有效分解食物中的粗蛋白及纖維素,促進(jìn)腸道益生菌的生長(zhǎng)[30-31]。
1.4 蟲草多肽(Cordymin)
蟲草多肽是從冬蟲夏草中提取的多肽類物質(zhì),其N端序列為AMAPPYGYRTPDAAQ,分子量為10906 Da,含量在冬蟲夏草中所占比例較小[32]。但是目前研究證實(shí),蟲草多肽具有很活躍的藥理學(xué)效用。Wang等[33]的研究表明,應(yīng)用蟲草多肽可以顯著拮抗炎癥因子IL-1β和TNF-α的水平,有效的降低血清中補(bǔ)體C3的含量,并且可以明顯的對(duì)抗動(dòng)物體內(nèi)脂質(zhì)過氧化物反應(yīng)(lipid peroxidation,LPO),抑制谷胱甘肽過氧化物酶(glutathione peroxidase,GPx),谷胱甘肽還原酶(glutathione reductase,GR),過氧化氫酶(catalase,CAT),Na+-K+-ATP酶,谷胱甘肽S-轉(zhuǎn)移酶(glutathione S transferase,GST)的活性,可以說,蟲草多肽具有抗氧化及抗炎的作用。另外,有學(xué)者也發(fā)現(xiàn),蟲草多肽還具有鎮(zhèn)痛的作用,可以強(qiáng)烈的對(duì)抗溶神經(jīng)素(neurolysin)對(duì)人體造成的疼痛刺激[34]。國(guó)內(nèi)學(xué)者對(duì)蟲草多肽研究后發(fā)現(xiàn),給予小鼠連續(xù)灌胃蟲草多肽30天,能提高小鼠的抗體生成細(xì)胞數(shù)和血清溶血素水平,促進(jìn)小鼠的單核—巨噬細(xì)胞碳廓清功能及腹腔巨噬細(xì)胞的吞噬能力。促進(jìn)小鼠的遲發(fā)型變態(tài)反應(yīng),顯著提高小鼠的自然殺傷細(xì)胞活性。由此可見,蟲草多肽具有增強(qiáng)小鼠免疫力功能作用[35]。而在最新的研究中也發(fā)現(xiàn),蟲草多肽可以明顯的降低糖尿病大鼠的血糖,刺激胰島素的分泌,保護(hù)胰島β細(xì)胞的損失,具有顯著的降血糖的作用[36]。
1.5 麥角甾醇(Ergosterol)
麥角甾醇是脂溶性維生素D2的前體,其次生代謝產(chǎn)物可產(chǎn)生麥角甾醇氧化物。上個(gè)世紀(jì)80年,中國(guó)的科學(xué)家從首次從冬蟲夏草中分離出麥角甾醇,之后開始對(duì)其進(jìn)行不斷的研究。蟲草中的麥角甾醇具有顯著的抗腫瘤作用[37]。有學(xué)者研究發(fā)現(xiàn),麥角甾醇可以發(fā)揮抗腫瘤活性,通過靶向阻礙JAK2/STAT3信號(hào)傳導(dǎo)通路激活從而抑制多發(fā)性骨髓瘤U266細(xì)胞血管生成,進(jìn)而達(dá)到殺死多發(fā)性骨髓瘤細(xì)胞的目的[38]。另外,麥角甾醇還具有顯著的抗炎效果。Kuo等[39]發(fā)現(xiàn),蟲草中提取的麥角甾醇可以顯著抑制動(dòng)物體內(nèi)T淋巴細(xì)胞的增殖,同時(shí)也明顯減少血液中白細(xì)胞介素2、白細(xì)胞介素4、白細(xì)胞介素10和干擾素-γ等細(xì)胞因子的水平。此外,蟲草中的麥角甾醇還具有顯著的抗纖維化作用,有學(xué)者研究證實(shí),麥角甾醇通過抑制細(xì)胞增殖和減弱細(xì)胞骨架蛋白表達(dá)并且直接阻礙轉(zhuǎn)化生長(zhǎng)因子-β1誘導(dǎo)的絲裂原活化蛋白激酶通路的激活可以有效抑制慢性腎炎中轉(zhuǎn)化生長(zhǎng)因子-β1引起的成纖維細(xì)胞活化[40]。
冬蟲夏草作為上述有效成分的結(jié)合體,所具有的多種藥理作用必然反映出其所含的有效成分的效能,同時(shí)也體現(xiàn)了中藥多組分、多環(huán)節(jié)、多靶點(diǎn)治療疾病的特點(diǎn)。
2.1 抗腫瘤作用
在冬蟲夏草眾多藥理學(xué)作用中,抗腫瘤作用是最早被人們所認(rèn)識(shí)并應(yīng)用于臨床治療中[41]。Chen等[42]通過實(shí)驗(yàn)發(fā)現(xiàn)冬蟲夏草可以增強(qiáng)人體造血細(xì)胞的活性,并且能夠顯著抑制人白血病U937細(xì)胞的增殖和分化,同時(shí)明顯的提高血液中干擾素-γ、腫瘤壞死因子-α、白細(xì)胞介素-1等抗腫瘤細(xì)胞因子的水平。Yang等[43]學(xué)者發(fā)現(xiàn),冬蟲夏草能夠通過激活Caspase-8信號(hào)通路同時(shí)抑制NF-kappa B信號(hào)通路達(dá)到明顯促進(jìn)大鼠MA-10睪丸間質(zhì)腫瘤細(xì)胞的凋亡。Park等[44]將冬蟲夏草的萃取液與NCI-H460移植瘤細(xì)胞共培養(yǎng)4周后發(fā)現(xiàn)與冬蟲夏草萃取液共培養(yǎng)的腫瘤細(xì)胞的生長(zhǎng)抑制率達(dá)到了80%以上,同時(shí)腫瘤的重量和體積也明顯的雖小。有學(xué)者之前已經(jīng)證明,冬蟲夏草的萃取液對(duì)各種癌細(xì)胞系具有有效的抑制效果,并在B16誘發(fā)的黑色素瘤C57BL/6J小鼠體內(nèi)檢測(cè)到抗腫瘤活性[45]。冬蟲夏草發(fā)揮上述抗腫瘤作用的機(jī)制可能是通過抑制核酸、蛋白質(zhì)合成或葡萄糖跨膜轉(zhuǎn)運(yùn),抑制腫瘤細(xì)胞的生長(zhǎng),同時(shí)間接通過促進(jìn)免疫細(xì)胞的增殖、分泌,增強(qiáng)免疫細(xì)胞的功能等發(fā)揮抗腫瘤作用[46]。
2.2 免疫調(diào)節(jié)作用
冬蟲夏草是一種非特異性免疫促進(jìn)劑,表現(xiàn)在正常或免疫功能低下時(shí),冬蟲夏草可能增強(qiáng)機(jī)體的免疫功能。Zhu等[47]的研究表明,給H22荷瘤小鼠服用冬蟲夏草可以顯著增強(qiáng)巨噬細(xì)胞的吞噬能力,促進(jìn)脾細(xì)胞的增殖和干擾素-γ和腫瘤壞死因子-α的水平。而另一方面,在免疫增強(qiáng)狀態(tài)下冬蟲夏草又發(fā)揮免疫抑制作用,顯示出對(duì)免疫功能的雙向調(diào)節(jié)作用。Zhang等[48]在給予心臟移植大鼠口服冬蟲夏草治療后發(fā)現(xiàn),冬蟲夏草可以有效抑制移植后的免疫反應(yīng),減少血液中免疫因子的水平,同時(shí)可以有效地對(duì)抗感染,延長(zhǎng)移植器官及動(dòng)物的生存時(shí)間。另外,有學(xué)者在體外試驗(yàn)中發(fā)現(xiàn)冬蟲夏草萃取物與C3H/HeJ小鼠Peyer’s patch細(xì)胞共培養(yǎng),之后取培養(yǎng)液的上清液再次與骨髓細(xì)胞進(jìn)行培養(yǎng)分析發(fā)現(xiàn),骨髓細(xì)胞的數(shù)量增加1.9倍。在光學(xué)顯微鏡下觀察發(fā)現(xiàn),與對(duì)照組相比,各種類型的骨髓細(xì)胞包括巨噬細(xì)胞樣及粒細(xì)胞樣的細(xì)胞明顯增多,而在上清液中證實(shí)了白細(xì)胞介素-6及巨噬細(xì)胞—粒細(xì)胞集落刺激因子的存在。從而推測(cè)冬蟲夏草可以通過激活巨噬細(xì)胞來調(diào)節(jié)白細(xì)胞介素-6的表達(dá), 同時(shí)提高造血生長(zhǎng)因子 (如Peyer’s patch細(xì)胞分泌的巨噬細(xì)胞—粒細(xì)胞集落刺激因子和白細(xì)胞介素-6 ) 的表達(dá), 后者作用于全身免疫系統(tǒng), 從而起到系統(tǒng)的免疫調(diào)節(jié)作用[49]。
2.3 抗氧化作用
天然冬蟲夏草可通過清除體內(nèi)羥自由基[50],抑制脂質(zhì)過氧化反應(yīng)。在體外,從冬蟲夏草的熱水提取物中檢測(cè)出了抗氧化活性,包括抑制亞油酸過氧化作用,對(duì)DPPH、羥基和超氧陰離子自由基清除能力以及亞鐵離子螯合能力。這項(xiàng)研究表明,冬蟲夏草的天然和人工培養(yǎng)的菌絲包含強(qiáng)有力的抗氧化劑活性,除了亞油酸過氧化反應(yīng)之外,在所有體外實(shí)驗(yàn)中測(cè)定的人工培養(yǎng)菌絲的抗氧化能力都優(yōu)于天然的菌絲。另一方面,冬蟲夏草熱水提取物被證實(shí)具有穩(wěn)定的氧化還原能力和金屬螯合能力。從這項(xiàng)研究中,有趣的是要注意培養(yǎng)菌絲體促使其使用在耗盡自然菌的強(qiáng)勁表現(xiàn)[51]。另有學(xué)者對(duì)鈷-60照射的BALB/c小鼠血清中丙二醛和超氧化物歧化酶抗氧化活性進(jìn)行檢測(cè),結(jié)果顯示,與鈷-60照射組相比,冬蟲夏草中、低劑量組小鼠血清中丙二醛的含量分別下降了17%和20%。而冬蟲夏草低、中、高劑量組的超氧化物歧化酶水平較鈷-60照射組分別提高了11%,2%和15%。提示冬蟲夏草提取物可以減少氧化應(yīng)激并且激活抗氧化酶活性從而達(dá)到增強(qiáng)動(dòng)物免疫力的作用[4, 52]。
2.4 降血糖作用
Lo等[53]的研究發(fā)現(xiàn),冬蟲夏草的子實(shí)體、菌絲以及發(fā)酵液都具有顯著的拮抗高血糖的作用。另有學(xué)者發(fā)現(xiàn),冬蟲夏草、牛磺酸和它們的組合經(jīng)口服后可以明顯降低糖尿病大鼠的血糖、果糖胺、總膽固醇及甘油三酯水平,同時(shí)還可以顯著降低胰島素抵抗指數(shù)和胰島丙二醛含量。另外,冬蟲夏草還可以顯著增加血清胰島素、高密度脂蛋白、還原型谷胱甘肽的含量,提高總抗氧化能力水平,改善胰腺β細(xì)胞功能[54]。Kan等[55]學(xué)者通過實(shí)驗(yàn)發(fā)現(xiàn),冬蟲夏草提取液能夠顯著升高高密度脂蛋白/低密度脂蛋白比率并能減輕體重。而且應(yīng)用冬蟲夏草治療可以有效控制高血糖并避免胰島素抵抗的發(fā)生。同時(shí)在體外MTT試驗(yàn)表明,冬蟲夏草保護(hù)鏈脲霉素的毒性對(duì)胰腺β細(xì)胞的損傷。
2.5 對(duì)腎臟保護(hù)作用
一項(xiàng)針對(duì)慢性移植腎病(chronic allograft nephropathy,CAN)患者服用冬蟲夏草治療6個(gè)月腎功能改善情況的研究發(fā)現(xiàn),冬蟲夏草可以明顯改善患者的血肌酐水平及肌酐清除率,而24小時(shí)尿蛋白定量、β2-微球蛋白含量及尿轉(zhuǎn)化生長(zhǎng)因子-β1水平明顯下降[56]。而冬蟲夏草對(duì)于急性腎功能衰竭也具有顯著的治療效果,其機(jī)制可能是保護(hù)腎小管上皮細(xì)胞鈉泵的活性;減弱腎小管上皮細(xì)胞溶酶體功能的過度表達(dá);減少腎小管上皮細(xì)胞脂質(zhì)過氧化反應(yīng)從而減輕毒性損傷[57]。另外也有學(xué)者研究表明,冬蟲夏草可以有效的減輕因脂多糖損傷引起的腎功能不全大鼠體內(nèi)PK1和MDCK細(xì)胞的死亡,同時(shí)可以顯著的改善腎血流量,腎小球?yàn)V過率,血漿尿素氮,肌酐水平及白細(xì)胞數(shù)量[58]。在保護(hù)腎臟缺血再灌注損傷方面,冬蟲夏草可以有效的減輕腎小管的損傷,增加基質(zhì)細(xì)胞衍生因子-1α及趨化因子受體4的表達(dá)。組織學(xué)研究表明冬蟲夏草可以誘導(dǎo)基質(zhì)細(xì)胞衍生因子-1α在腎小囊,腎小球系膜細(xì)胞,遠(yuǎn)曲小管和近曲小管的鱗狀細(xì)胞上進(jìn)行表達(dá),從而減輕缺血再灌注造成的組織損傷[59]。
冬蟲夏草的藥理學(xué)作用十分廣泛,除了上述的作用外,人們還發(fā)現(xiàn)冬蟲夏草可以降血脂、改善心肌血流量、緩解心律失常、抑制血小板聚集、防止肝纖維化、止咳平喘等。特別是在抗炎以及抗氧化等藥效學(xué)方面具有明顯優(yōu)勢(shì),但其機(jī)制與原理尚需做進(jìn)一步探索。至今為止,尚未有學(xué)者對(duì)冬蟲夏草對(duì)骨質(zhì)疏松癥作用進(jìn)行直接的研究,目前相關(guān)報(bào)道間接地提示冬蟲夏草可以調(diào)節(jié)細(xì)胞骨架的重組[60],增強(qiáng)成骨細(xì)胞分化[61],但是具體的作用效果還缺乏相關(guān)的實(shí)驗(yàn)證據(jù)。
冬蟲夏草的藥理學(xué)作用十分廣泛,但是目前人們對(duì)于它的藥用價(jià)值的認(rèn)識(shí)還很有限,能夠進(jìn)一步挖掘出冬蟲夏草的藥理學(xué)作用具有重要意義。隨著冬蟲夏草藥理學(xué)研究的不斷深入,其發(fā)揮作用的有效單體成分逐一被分離并驗(yàn)證,將進(jìn)一步增加人們對(duì)于冬蟲夏草的認(rèn)識(shí),同時(shí)也為臨床開發(fā)出毒副作用小,療效明顯且具有自主知識(shí)產(chǎn)權(quán)的藥物提供理論依據(jù)。
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(本文編輯:秦楠)
PharmacologicalstudyprogressoftheCordycepssinensis
QIWei,LEIWei,YANYa-bo,etal.
DepartmentofOrthopaedics,XijingHospital,TheFourthMilitaryMedicalUniversity,Xi’an710032,China
Correspondingauther:QIWei,E-mail:chris.qi.wei@gmail.com
Cordycepssinensis, a kind of famous and precious traditional Chinese medicine, is rich in a variety of active ingredients such as Cordyceps Polysaccharide, Cordycepin, Cordycepic acid, Cordymin and Ergosterol. Modern medicine has found extensive pharmacological actions ofCordycepssinensisincluding anti-tumor, immunomodulatory, hypoglycemic, anti-oxidation and the protective effect of kidney function. The present study has confirmed thatCordycepssinensisand monomeric active ingredients are useful in treatment of many diseases. This paper summarizes the study progress of the pharmacological action ofCordycepssinensisand its monomeric active ingredients from two aspects: the research status of the monomeric active ingredients and the pharmacological effects ofCordycepssinensisbased on retrieving information in recent years, and aims to contribute to the further exploitation and application ofCordycepssinensis.
Cordycepssinensis; Monomeric active ingredients; Pharmacological action
710032 西安,第四軍醫(yī)大學(xué)西京骨科醫(yī)院骨四科[漆偉(博士研究生)、雷偉、嚴(yán)亞波、張揚(yáng)、劉帥(博士研究生)、曹鵬沖(博士研究生)、樊勇];解放軍第520醫(yī)院外科(漆偉)
漆偉(1983- ),2011級(jí)在讀博士研究生,主治醫(yī)師。研究方向:脊柱內(nèi)固定生物力學(xué)研究、骨質(zhì)疏松癥的藥物治療。E-mail: chris.qi.wei@gmail.com
R285
A
10.3969/j.issn.1674-1749.2014.03.020
2014-01-12)