銆€姝︽眽鐢熺墿鍒跺搧鐮旂┒鎵€鐙傜姮鐥呮娴嬩腑蹇?/span>
銆€銆€銆€閫氫俊浣滆€咃細涓ュ鏂帮紝Email: yanjx45@163.com
1. 鐙傜姮鐥呯柅鑻楀彂灞曞彶涓婄殑閲嶈閲岀▼纰?/span>
鏈€杩戯紝鍥介檯涓婄媯鐘梾鐤嫍鐨勭爺绌跺彇寰椾簡閲嶅ぇ绐佺牬銆?/span>Dietzschold灏忕粍鐮斿彂鍑轰竴绉?/span>鏂板瀷鐙傜姮鐥呭噺姣掓椿鐤嫍锛岃鐤嫍涓庝互寰€鐙傜姮鐥呯柅鑻楃浉姣旓紝鏁堝姏鏇撮珮鑰屼笖楂樺害瀹夊叏锛岀敋鑷?/span>鏈?/span>鍙兘鐢ㄤ簬
鐙傜姮鐥呭彂鐥呭悗鐨勬棭鏈熸不鐤椼€?/span>2009骞?/span>7鏈?/span>6鏃?/span>鐨勮嫳鍥姐€?/span>NATURE銆嬫潅蹇?/span>[1]鍜?/span>7鏈?/span>7鏃?/span>鐨勩€婄編鍥界瀛﹂櫌闄㈡姤銆?/span> [2]鍒嗗埆鍙戣〃浜嗙浉鍏虫柊闂诲拰璁烘枃銆?/span>
杩欓」鎴愭灉鐢辩編鍥借垂鍩庢澃鏂愰€婂ぇ瀛︾殑Dietzschold鍗氬＋棰嗗鐨勪竴缁勭梾姣掑瀹跺拰鍏嶇柅瀛﹀鍙栧緱銆備粬浠埄鐢ㄥ弽鍚戦仐浼犲鎶€鏈敼閫犵媯鐘梾鐥呮瘨锛屽紑鍙戝嚭楂樺害鍑忔瘨鐨勭媯鐘梾娲荤梾姣掔柅鑻椼€?/span>姝ら」杩涘睍鏄嚜鐙傜姮鐥呯柅鑻楄癁鐢熶竴鐧惧骞存潵鐨勪竴涓噸瑕侀噷绋嬬锛屾瀬鏈夊彲鑳芥垚涓虹媯鐘梾鐤嫍鍙戝睍鍙蹭笂涓€涓噸澶ц浆鎶樼偣銆?/span>
甯歌鐢ㄤ簬鏆撮湶鍚庢帴绉嶇殑浜虹敤鐙傜姮鐥呯柅鑻楀惈鏈夌伃娲荤梾姣掞紝瀹冧滑涓嶈兘鍦ㄤ綋鍐呯敓闀挎垨澧炴畺锛岃姹傚娆℃帴绉嶆墠鑳戒骇鐢熼€傚綋鐨勫厤鐤弽搴斻€傝€屽父瑙勭殑鍑忔瘨娲荤柅鑻楋紙鐜颁富瑕佺敤浜庨噹鐢熷姩鐗╋級鍚湁鍑忔瘨鐨勬椿鐥呮瘨锛屽畠浠櫧鐒惰兘姣旂伃娲荤梾姣掕瀵兼洿寮虹殑鍏嶇柅鍙嶅簲锛屼絾瀹冧滑鏈韩鍙兘寮曡捣鐤剧梾锛屽緢闅惧厖鍒嗕繚璇佸叾瀹夊叏鎬с€?/span>Dietzschold鍜屼粬鐨勭爺绌跺皬缁勭爺鍒剁殑鏂板瀷鐤嫍鏃㈣兘涓庣伃娲荤柅鑻椾竴鏍峰畨鍏紝鍗充娇鍦ㄦ柊鍑虹敓鐨勫辜榧犺剳鍐呮帴绉嶏紝涔熷彲浠ョ‘淇濅笉寮曡捣鐤剧梾锛涘悓鏃跺張姣斿叾瀹冨噺姣掓椿鐤嫍鏇村姞鏈夋晥銆傜洰鍓嶅浜虹被鐨勬毚闇插悗娌荤枟锛屽繀椤诲湪鏆撮湶鍚?/span>20灏忔椂鍐呭紑濮嬫帴绉嶇柅鑻楋紝 鑰屾柊鍨嬬柅鑻?/span>涔熷彲浠ュ湪鏆撮湶鍚庤緝鏅氳繘琛屾帴绉嶏紱鍗充娇鍙戠梾鐨勬棭鏈熺棁鐘跺凡鍑虹幇锛屽崟娆℃帴绉嶄篃瓒充互浠庡叾浣撳唴娓呴櫎鐥呮瘨[1]銆?/span>
Dietzschold绛夌爺鍒舵柊鍨嬬柅鑻楅噰鐢ㄧ殑鍩烘湰鏂规硶鏄鐥呮瘨鐨勮〃闈㈢硸铔嬬櫧锛?/span>glycoprotein, GP锛?/span>杩涜閬椾紶瀛︿慨鏀广€?/span>GP鍦ㄤ汉浣撶殑鍏嶇柅绯荤粺涓兘鍙戞尌鐩稿綋浜庤缃閽熺殑浣滅敤锛屼絾閫氬父瀹冪殑浜ч噺闈炲父浣庯紝鏃犳硶鍏呭垎鍙戞尌鍚姩浣撳唴鐨勯槻寰＄郴缁熺殑浣滅敤銆?/span>Dietzschold绛夊皢GP鍩哄洜鐨勪笁涓嫹璐濆悓鏃舵彃鍏ュ埌鐥呮瘨鍩哄洜缁勫悗锛屽彲琛ㄨ揪澶ч噺鐨?/span>GP锛岃繖灏变负鍏嶇柅绯荤粺鍒涢€犱簡涓€涓洿濂界殑闈舵爣锛屽彲浠ュ揩閫熷惎鍔ㄥ厤鐤弽搴斿苟鎻愬崌鍏嶇柅鍙嶅簲鐨勬按骞筹紝浠庤€岃兘闃叉鐥呮瘨杩涗竴姝ヨ敁寤躲€傚悓鏃讹紝涓轰簡纭繚鏂板瀷鐤嫍姣掓牚鐨勫畨鍏ㄦ€э紝浠栦滑棰勫厛鏀瑰彉GP搴忓垪涓殑涓や釜姘ㄥ熀閰镐娇鍏舵垚涓烘棤姣?/span>GP锛屼粠鑰岃兘娑堥櫎璇ユ瘨鏍殑姣掑姏銆備粬浠皢鍚?/span>3涓棤姣?/span>GP鐨勬瘨鏍洿鎺ユ敞灏勫埌鍋ュ悍鐨?/span>5d榫勫辜榧犲ぇ鑴戜腑锛岀粨鏋滄病鏈夋樉绀轰换浣曠媯鐘梾杩硅薄锛岃繖鎰忓懗鐫€璇ユ瘨鏍瘮鍏跺畠鍑忔瘨娲荤柅鑻楁墍鐢ㄦ瘨鏍畨鍏ㄥ緱澶氥€備负浜嗛獙璇佹墍鐮斿彂鍑忔瘨鏍殑鏈夋晥鎬э紝浠栦滑鐢ㄨ嚧姝绘€х媯鐘梾鐥呮瘨鏍劅鏌撴垚骞村皬榧狅紝閲囩敤鑲岃倝娉ㄥ皠鎴栬剳鍐呮敞灏勶紝缁撴灉鍙戠幇鍦ㄦ毚闇插悗3d鍐呮帴绉嶆柊鐤嫍浠嶅彲浠ラ槻姝㈠彂鐥呫€傝鐤嫍鐢ㄤ簬鏆撮湶鍓嶅鐞嗕篃鏈夎壇濂芥晥鏋滐紝鑰岀洰鍓嶇媯鐘梾鐤嫍涓昏鏄互杩欑鏂瑰紡鐢ㄤ簬閲庣敓鍔ㄧ墿鍜岀嫍銆傚皬榧犲湪3鍛ㄥ墠鎺ョ涓€娆¤鐤嫍锛岀劧鍚庣敤鑷存鎬х梾姣掕繘琛屾劅鏌擄紝缁撴灉灏忛紶涓嶅彂鐥咃紝杩欒瘉鏄庤鐤嫍鐩稿綋瀹夊叏鑰屼笖鏈夋晥锛屽彲浠ヨ€冭檻浣滀负涓€绉嶄竴娆℃敞灏勭粓鐢熸湁鏁堢殑鐤嫍銆?/span>
2. GP涓庣媯鐘梾鐥呮瘨鑷寸梾鎬у拰鍏嶇柅鍘熸€х殑鍏崇郴
鐙傜姮鐥呯梾姣掑熀鍥犵粍鏍搁吀涓轰笉鍒嗚妭娈电殑鍗曡偂璐熼摼RNA锛岀敱11928鎴?/span>11932涓牳鑻烽吀缁勬垚锛屽叾3’鍒?/span>5’绔緷娆℃帓鍒楃潃N銆?/span>P銆?/span>M銆?/span>G鍜?/span>L鍩哄洜锛屽垎鍒紪鐮?/span>5绉嶇粨鏋勮泲鐧斤細鏍歌泲鐧?/span>(nucleoprotein锛?/span>NP)銆佺７閰稿寲铔嬬櫧(phosphoprotein锛?/span>PP)銆佽啘鍩鸿川铔嬬櫧(matrix protein锛?/span>MP)銆佺硸铔嬬櫧(glyeoprotein锛?/span>GP)鍜岃浆褰曢叾澶ц泲鐧?/span>(1arge protein锛?/span>LP)锛?/span>NP銆?/span>PP銆?/span>LP鍜屽熀鍥犵粍RNA鍏卞悓鏋勬垚鏍歌泲鐧藉鍚堜綋(nucleoprotein complex锛?/span>RNP) [3]銆傜媯鐘梾鐥呮瘨鐨勫叆渚点€佹劅鏌撱€佸鍒朵互鍙婅嚧鐥呯瓑杩囩▼鍧囨槸閫氳繃鍏剁粨鏋勫拰鍔熻兘铔嬬櫧鏉ュ畬鎴愩€?/span>
2.1 GP涓庣媯鐘梾鐥呮瘨鑷寸梾鎬х殑鍏崇郴
GP鏃犺浠庣粨鏋勪笂鎴栧厤鐤按骞充笂閮芥槸琚爺绌舵渶澶氱殑涓€绉嶇媯鐘梾鐥呮瘨铔嬬櫧锛屽畠鏃㈡槸鐙傜姮鐥呯梾姣掍笌缁嗚優鍙椾綋缁撳悎鐨勯厤浣擄紝鍙堟槸鏈夋晥鐨勪繚鎶ゆ€ф姉鍘燂紝鑳借瀵间骇鐢熶腑鍜屾姉浣撳拰鍒烘縺缁嗚優鍏嶇柅搴旂瓟[4]銆?/span>GP涓庣媯鐘梾鐥呮瘨姣掑姏瀛樺湪鐫€瀵嗗垏鐨勫叧绯汇€傞鍏堬紝瀹冭兘鍚姩鐥呮瘨涓庣粏鑳炵壒寮傛€у彈浣撶殑缁撳悎锛屽洜姝ゅ畠鍦ㄧ梾姣掔殑缁勭粐鍡滄€т笂璧峰喅瀹氭€т綔鐢紱鍏舵锛?/span>GP鑳藉寰堝ソ鍦颁笌RNA-NP-MP澶嶅悎鐗╃浉浜掍綔鐢ㄤ互甯姪鐥呮瘨鍑鸿娊閲婃斁锛涘悓鏃讹紝GP琛ㄨ揪缁存寔鍦ㄦ渶浣庢按骞筹紝鑳介槻姝㈣鎰熸煋鐨勭缁忕粏鑳炲彂鐢熷姛鑳界己鎹熶粠鑰岄€冮伩瀹夸富鐨勫厤鐤簲绛旓紝涓虹媯鐘梾鐥呮瘨鍦ㄧ缁忕郴缁熷唴鐨勬挱鏁ｆ彁渚涗簡鍩虹[5]銆傚綋GP姘ㄥ熀閰稿簭鍒椾腑姘ㄥ熀閰告畫鍩哄彂鐢熸敼鍙樻椂锛岀媯鐘梾鐥呮瘨鐨勬瘨鍔涗細鍙楀埌褰卞搷銆傚綋鐙傜姮鐥呯梾姣掔硸铔嬬櫧鑶滃鍖?/span>330浣嶇殑璧栨皑閰稿拰333浣嶇殑绮炬皑閰稿垎鍒澶╅棬鍐皑閰稿拰鐢茬～姘ㄩ吀鍙栦唬鏃讹紝瀹冧細鏄庢樉闄嶄綆GP鍜岀缁忕槫缁嗚優涔嬮棿鐨勭浉浜掍綔鐢紝瀵艰嚧璇ュ弻绐佸彉鐙傜姮鐥呯梾姣掓牚瀵规垚骞村皬榧犳病鏈夎嚧鐥呮€?/span>[6]銆傚叾瀹冪殑鐮旂┒鍙戠幇锛屽綋鐙傜姮鐥呯梾姣掔殑GP姘ㄥ熀閰稿簭鍒楃殑绗?/span>333浣嶇簿姘ㄩ吀琚紓浜皑閰搞€佽胺閰拌兒銆佽胺姘ㄩ吀鎴栫敇姘ㄩ吀鏇挎崲鍚庯紝涓嶇浠ヤ綍绉嶅墏閲忎綍绉嶉€斿緞鎰熸煋灏忛紶锛屽潎鏃犺嚧鐥呮€с€傝繖浜涢兘琛ㄦ槑GP涓333浣嶇簿姘ㄩ吀鍐冲畾浜嗙媯鐘梾鐥呮瘨鍦ㄧ缁忕郴缁熷唴鐨勬挱鏁ｆ€?/span>[7] 銆?/span>Takayama-lto绛夌爺绌跺彂鐜帮紝闈炶嚧鐥呮€х媯鐘梾鐥呮瘨鏍殑绗?/span>194浣嶇殑澶╁啲閰拌兒鑻ヨ璧栨皑閰告浛鎹紝鑳藉鑷村叾姣掑姏澧炲己鑰屼娇鐥呮瘨瀵瑰涓荤殑鑷寸梾鑳藉姏鎻愰珮[8]銆?/span>
2.2 GP涓庣媯鐘梾鐥呮瘨鍏嶇柅鍘熸€х殑鍏崇郴
GP鏄媯鐘梾鐥呮瘨涓渶鏈夋晥鐨勪繚鎶ゆ€ф姉鍘燂紝瀹冧篃鏄敮涓€鑳借瀵间綋娑插厤鐤殑鐙傜姮鐥呯梾姣掕〃闈㈡姉鍘燂紝涓嶄粎璇卞鏈轰綋浜х敓涓拰鎶椾綋瀹炵幇浣撴恫鍏嶇柅锛屽悓鏃朵篃鏄満浣撳疄鐜扮粏鑳炲厤鐤殑鑹ソ鎶楀師銆傚叾鑶滃鍖哄喅瀹氫簡鐙傜姮鐥呯梾姣掔殑鎶楀師鐗规€э紝璇ュ尯娈靛井灏忕殑鍙樺寲鍗冲彲鑳藉奖鍝嶅埌鐥呮瘨鐨勬姉鍘熸€с€?/span>
鐢ㄥ崟鍏嬮殕鎶椾綋涓拰璇曢獙鐮旂┒GP鍒嗗瓙涓婄殑鎶楀師缁撳悎浣嶇偣锛屽彂鐜?/span>GP涓婅嚦灏戝瓨鍦?/span>3涓腑鍜屾姉浣撶粨鍚堜綅鐐癸細GI銆?/span>G鈪?/span>鍜?/span>G鈪?/span>銆?/span>G鈪?/span>鍜?/span>G鈪?/span>涓嶄絾鏄瀵间骇鐢熶腑鍜屾姉浣撶殑鎶楀師琛ㄤ綅锛岃€屼笖涔熸槸GP鎶樺彔鍜岃繍杈撶殑蹇呴渶閮ㄥ垎銆?/span>GP鎶楀師鎬у彉鍖栦富瑕佹槸鐢?/span>GII浣嶇偣涓?/span>34锝?/span>42浣嶃€?/span>147浣嶃€?/span>184浣嶃€?/span>198锝?/span>200浣嶆皑鍩洪吀锛屼互鍙?/span>G鈪?/span>浣嶇偣涓?/span>330锝?/span>340浣嶆皑鍩洪吀鐨勬浛鎹㈠紩璧凤紝GP涓婂崟涓€姘ㄥ熀閰哥殑鏀瑰彉鍗宠兘鏀瑰彉鐙傜姮鐥呯梾姣掔殑鎶楀師鎬с€?/span>Irie绛?/span>[9]鐢ㄥ崟鍏嬮殕鎶椾綋鐮旂┒鐙傜姮鐥呯梾姣?/span>GP涓婄殑1涓瀯璞¤〃浣嶆椂鍙戠幇锛岀36浣嶈嫃姘ㄩ吀琚劘姘ㄩ吀鏇挎崲褰㈡垚鐨勭獊鍙樻牚涓㈠け浜嗚繖涓€鎶楀師琛ㄤ綅锛屽崟鍏嬮殕鎶椾綋灏变笉鑳戒腑鍜岃绐佸彉鏍紱绗?/span>39浣嶄笣姘ㄩ吀琚嫃姘ㄩ吀鏇挎崲褰㈡垚鐨勭獊鍙樻牚铏借兘涓庡崟鍏嬮殕鎶椾綋缁撳悎锛屼絾鍏剁┖闂存瀯璞″彂鐢熶簡鏀瑰彉锛屽崟鍏嬮殕鎶椾綋宸蹭笉鑳戒腑鍜岀獊鍙樻牚銆?/span>
3.銆€鏂板瀷鐙傜姮鐥呭噺姣掓椿鐤嫍鐨勪富瑕佷紭鐐?/span>
瀵瑰悎鏍肩殑鏈夊疄鐢ㄤ环鍊肩殑鐙傜姮鐥呯梾姣掑噺姣掓椿鐤嫍鐨勫熀鏈姹傛湁5椤?/span>[10]锛?/span>鈶?/span>瀹夊叏鎬э細灏?/span>鑷寸梾鍙兘鎬ч檷鑷虫渶浣庯紱鈶?/span>鏈夋晥鎬э細鍦ㄥ彈璇曞璞′腑鑳藉浜х敓瓒冲鐨勫厤鐤繚鎶ゅ姏锛?/span>鈶?/span>閬椾紶绋冲畾鎬э紱鈶?/span>鐑ǔ瀹氭€э紱鈶?/span>楂樹骇锛氱柅鑻楁瘨鏍?/span>鍦ㄧ粍缁囧煿鍏讳腑鑳藉杈惧埌杈冮珮鐨勬淮搴︼紙鏁堜环锛夈€傛柊鍨嬬媯鐘梾鍑忔瘨娲荤柅鑻楀叏闈㈢鍚堣繖5椤瑰熀鏈姹傘€?/span>
3.1 娑堥櫎鎴栭檷浣庣媯鐘梾鐥呮瘨鐨勮嚧鐥呮€э紙瀹夊叏鎬э級
GP涓婄殑333浣嶇簿姘ㄩ吀鎴栬禆姘ㄩ吀鏄媯鐘梾鐥呮瘨鑷寸梾鍐冲畾鍥犲瓙锛屽洜姝わ紝杩欎釜娈嬪熀琚€変负浜х敓鍑忔瘨鏍殑闈朵綅鐐?/span>[11]銆備负浜嗘秷闄ょ媯鐘柅鑻楁牚SPBN鐨勮嚧鐥呮€э紝Faber绛?/span>[5]灏?/span>SPBN GP姘ㄥ熀閰稿簭鍒楃殑绗?/span>333浣嶇簿姘ㄩ吀鏇挎崲涓鸿胺姘ㄩ吀锛?/span>Arg333 →Glu333锛夛紝骞跺皢杩欎釜鍚湁绐佸彉鐨勫噺姣掓牚鍛藉悕涓?/span>SPBNGA銆傚悓鏃朵负浜嗗鍔犺鐤嫍鏍殑鍏嶇柅鍘熸€э紝浠栦滑鍙堢敤涓や釜绐佸彉鐨?/span>G鍩哄洜鍙栦唬鍘熸潵鐨勪竴涓?/span>G鍩哄洜鑰屾瀯寤轰簡鍑忔瘨鏍?/span>SPBNGA-GA銆?/span>Blanton绛?/span>[12-14]鐨?/span>鐮旂┒琛ㄦ槑锛屽皢SPBNGA鍜?/span>SPBNGA-GA鍑忔瘨鏍劅鏌撶嫍銆佹担鐔婂拰鐛寸瓑鍔ㄧ墿鍚庯紝娌℃湁寮曡捣鐙傜姮鐥呭拰浠讳綍鐨勭浉鍏崇棁鐘躲€傜敤涓変釜鏃犳瘨鐨?/span>G鍩哄洜鍙栦唬鍘熸潵鐨勪竴涓?/span>G鍩哄洜鑰屾瀯寤虹殑鍑忔瘨鏍?/span>SPBNGAS-GAS-GAS鍒欒繘涓€姝ラ檷浣庝簡鍥炲绐佸彉鎴愯嚧鐥呮瘨鏍殑鍙兘鎬э紝浠庤€岃繘涓€姝ユ彁楂樹簡瀹夊叏鎬?/span>[2]銆?/span>
3.2 鎻愰珮鐤嫍鐨勫厤鐤師鎬э紙鏈夋晥鎬э級
鐙傜姮鐥呯梾姣掑噺姣掓牚GP鐨勮〃杈炬按骞冲強鍏朵績杩涚粏鑳炲噵浜＄殑鑳藉姏鐩存帴鍐冲畾浜嗗畠寮曡捣鍏嶇柅搴旂瓟鐨勫己搴?/span>[15 ]銆備负浜嗗寮哄噺姣掓椿鐤嫍姣掓牚鐨勫厤鐤師鎬э紝Faber绛?/span>[5]鍦ㄥ噺姣掔媯鐘梾鐥呮瘨鍩哄洜缁勪腑鎻掍汉棰濆鐨?/span>G鍩哄洜锛屼互澧炲姞GP鍦ㄦ劅鏌撶粏鑳炰腑鐨勮〃杈炬按骞炽€傚湪璇ラ」鐮旂┒涓紝Faber绛夋瀯寤轰簡鍚湁2涓浉鍚?/span>G鍩哄洜鐨勯噸缁勭媯鐘梾鐥呮瘨SPBNGA-GA鏍紝杩?/span>2涓?/span>G鍩哄洜鍧囧寘鍚簡鍑忔瘨鐩稿叧绐佸彉锛屽嵆濡傚墠杩板湪GP鐨?/span>333浣嶇偣鐨勬皑鍩洪吀娈嬪熀鏈夋敼鍙樸€傚悓鏃讹紝Faber绛夐€氳繃鍏嶇柅娌夋穩鍜屾祦寮忕粏鑳炰华鍒嗘瀽鍙戠幇锛屼笌鍚湁鍗曚釜G鍩哄洜鐨勭梾姣?/span>(SPBNGA鏍?/span>)鐩告瘮锛屽湪鎰熸煋浜?/span>SPBNGA-GA姣掓牚鐨勫煿鍏荤粏鑳炰腑鑳戒骇鐢?/span>2鍊嶇殑GP锛岃€屼笖鍚庤€呮墍璇卞鐨勭粏鑳炲噵浜℃洿涓哄己鐑堛€備粬浠篃鍙戠幇锛岀敤SPBNGA-GA鏍厤鐤殑灏忛紶姣旂敤SPBNGA鏍彲浜х敓鏇翠负鏈夋晥鐨勪繚鎶ゆ€у厤鐤€?/span>Faber绛?/span>[2]灏?/span>SPBNGA鍑忔瘨鏍?/span>GP涓?/span>194浣嶇殑澶╁啲姘ㄩ吀琚浛鎹负涓濇皑閰告瀯寤轰簡鏂扮殑鍑忔瘨鏍?/span>SPBNGAS锛岃€屽悗鎶婅GP鍩哄洜澶嶅埗涓や唤鏋勫缓鍑轰竴绉嶅惈3涓獊鍙?/span>GP鍩哄洜鐨勬柊鍨嬮珮搴﹀噺姣掓牚SPBNGAS-GAS-GAS锛岃繖绉嶅噺姣掓椿鐤嫍瀵规柊鐢熷皬榧犵敋鑷虫槸鍏嶇柅鍔熻兘瀛樺湪缂洪櫡鐨勫皬榧犻兘娌℃湁鑷寸梾鎬э紝骞朵笖鍏锋湁鑹ソ鐨勫厤鐤師鎬с€傚畠鑳藉湪灏忛紶鍜岄潪浜虹伒闀跨被鍔ㄧ墿涓揩閫熻鐢熸湁鏁堢殑鎶楃媯鐘梾鍏嶇柅鍙嶅簲锛屼互鑷充竴娆℃帴绉嶅氨鑳藉鎻愪緵瀹屽叏鐨勪繚鎶や綔鐢紱鑰屼笖锛岃鐤嫍鍦ㄦ毚闇插墠鍜屾毚闇插悗鎺ョ鍧囨湁鏁堛€?/span>
3.3 鎻愰珮鐤嫍鐨勯仐浼犵ǔ瀹氭€с€佺儹绋冲畾鎬у強鍦ㄧ粏鑳炲煿鍏讳腑鐨勬淮搴︼紙楂樹骇锛?/span>
閲嶇粍鐥呮瘨鍦ㄥ惈鏈夊噺姣掔浉鍏崇獊鍙樼殑鎯呭喌涓嬶紝鐥呮瘨鍦ㄦ帴绉嶅姩鐗╃殑浣撳唴杩涜绻佹畺鐨勮繃绋嬩腑锛岀敱浜庢煇绉嶇獊鍙樺Θ纰嶄簡鐥呮瘨鍑忔瘨鐗规€х殑琛ㄧ幇锛岃鐥呮瘨鏈夊彲鑳藉彉鎴愯嚧鐥呮牚銆傛墍浠ョ媯鐘梾鍑忔瘨娲荤柅鑻楀繀椤诲叿鏈夎壇濂界殑閬椾紶绋冲畾鎬с€?/span>Faber绛夐€氳繃鍦ㄦ柊鐢熷皬榧犱腑灏嗛噸缁勭梾姣掔柅鑻椾紶浠ｅ彂鐜帮細鍑忔瘨鏍?/span>SPBNGA 骞朵笉绋冲畾锛屽湪浼犱唬鐨勮繃绋嬩腑鍏?/span>GP涓?/span>194浣嶇殑澶╁啲姘ㄩ吀绐佸彉涓鸿禆姘ㄩ吀锛堝懡鍚嶄负SPBNGAK鏍級锛屽苟鎭㈠浜嗚嚧鐥呮€с€傚叿鏈夎嚧鐥呮€х殑SPBNGAK鏍湪浣撳唴鍜屼綋澶栭兘琛ㄧ幇鍑哄緢寮虹殑鎾暎鎬э紝鍙互蹇€熸劅鏌撶粏鑳炲苟淇冭繘缁嗚優鑶滆瀺鍚?/span>[7]銆備负浜嗕娇閲嶇粍鐨勭梾姣掕兘澶熺ǔ瀹氾紝Faber 绛夊皢SPBNGA鍑忔瘨鏍?/span>GP涓?/span>194浣嶇殑澶╁啲姘ㄩ吀鏇挎崲涓轰笣姘ㄩ吀鏋勫缓浜嗘柊鐨勫噺姣掓牚SPBNGAS锛岃€屽悗鎶?/span>GP鍩哄洜澶嶅埗鏋勫缓鎴?/span>SPBNGAS-GAS鏍€傚啀灏嗚繖浜涘噺姣掓牚鍦ㄥ皬榧犱腑浼犱簲浠ｅ悗鍙栨柊鐢熷皬榧犵殑鑴戠粍缁囧垎绂荤梾姣掑苟鍒嗘瀽RNA搴忓垪锛屽彂鐜板苟鏈嚭鐜板熀鍥犵獊鍙樻垨缂哄け銆傚悓鏃讹紝璇ョ爺绌剁粍鐢?/span>SPBNGAS鏍粡棰呭唴鎰熸煋绗簲浠ｅ皬榧狅紝鍙戠幇骞舵湭寮曡捣灏忛紶鍙戠梾鎴栨浜★紝浜嬪疄璇佹槑杩欎竴鏇挎崲甯︽潵浜嗙ǔ瀹氭€э紝浣嗘病鏈夊鍔犲噺姣掓牚鐨勮嚧鐥呮€э紝璇存槑涓濇皑閰告浛鎹㈠ぉ鍐皑閰告槸鍙鐨勩€備负浜嗚瘉鏄庢槸鍚︿负澶嶅埗鐨?/span>GA鍩哄洜褰卞搷浜嗗噺姣掓牚鐨勯仐浼犵ǔ瀹氭€э紝鐮旂┒浜哄憳[16]鍒嗗埆娴嬭瘯鍖呮嫭GA鍜?/span>GAK鍩哄洜鐨勬瘨鏍紙SPBNGA-GAK鍜?/span>SPBNGAK-GA锛夛紝浠ュ強鍚袱涓?/span>GAK鍩哄洜鐨勬瘨鏍紙SPBNGAKGAK锛夛紝缁撴灉鍙戠幇SPBNGAKGAK鍏锋湁鑷寸梾鎬э紝鑰?/span>SPBNGA-GAK鍜?/span>SPBNGAK-GA閮芥棤鑷寸梾鎬с€傝繖浜涜鏄?/span>GA鍩哄洜鍐冲畾鐨勯潪鑷寸梾鎬у己浜?/span>GAK鍩哄洜鍐冲畾鐨勮嚧鐥呮€э紝Faber绛夋瀯寤虹殑姣掓牚SPBNGAS-GAS-GAS鍏锋湁楂樺害鍑忔瘨鎬т篃璇佹槑浜嗚繖涓€鐐广€?/span>
瀵逛簬鐙傜姮鐥呭噺姣掔柅鑻楁潵璇达紝搴斿叿鏈夎壇濂界殑娓╁害閫傚簲鎬э紙鐑ǔ瀹氭€э級锛屽嵆鍦ㄤ竴瀹氱殑娓╁害鑼冨洿鍐呬粛鑳戒繚鎸佹劅鏌撳姏銆?/span>绛?/span>[17]灏嗗噺姣掓牚SPBNGA鍜?/span>SPBNGA-GA鏀剧疆鍦ㄤ笉鍚岀殑娓╁害锛?/span>4锛?/span>25鍜?/span>37鈩?/span>锛変竴瀹氱殑鏃堕棿锛?/span>14d锛夊悗鍙戠幇锛屽畠浠湪4鈩?/span>鏉′欢涓嬫斁缃袱鍛ㄥ彲浠ュ熀鏈繚鎸佹淮搴︿笉鍙橈紝鍙湁鍦?/span>37鈩?/span>鐨勬潯浠朵笅婊村害瀛樺湪涓€瀹氬樊寮傘€傝鏄庡惈鏈夐澶?/span>GA鍩哄洜鐨?/span>SPBNGA-GA鍦ㄦ甯告潯浠朵笅骞舵湭寮曡捣鐥呮瘨鐑ǔ瀹氭€х殑鏄庢樉鍙樺寲锛岃繖缁欏噺姣掓椿鐤嫍鍦ㄤ繚瀛樻柟闈㈡彁渚涗簡璐ㄩ噺淇濊瘉銆?/span>
鑳藉惁鍦ㄧ粏鑳炲煿鍏讳腑鑾峰彇楂樻淮搴︾殑鐥呮瘨锛屽喅瀹氫簡鐙傜姮鍑忔瘨娲荤柅鑻楁槸鍚﹀叿鏈夊晢涓氫环鍊笺€?/span>Dietzschold 绛?/span>[17]閲囩敤鍦ㄧ敓鐗╁弽搴旂郴缁熶腑浼樺寲鍩瑰吇鏉′欢锛屽湪BSR缁嗚優涓煿鍏?/span>SPBNGA鍜?/span>SPBNGA-GA鏍椂鍙戠幇鍏舵渶楂樻淮搴﹀彲浠ュ垎鍒彲杈惧埌1×1010 FFU/ml鍜?/span>9.3×109 FFU/ml锛岃鏄庤繖浜涘噺姣掔殑鐤嫍鏍€傜敤浜庡晢涓氭€уぇ瑙勬ā鐢熶骇銆?/span>
4. 灞曟湜
涓栫晫鍗敓缁勭粐鍊¤锛屽埌2020骞村湪鍏ㄧ悆娑堢伃鐙傜姮鐥呫€備笉涔呭墠锛屼笘鐣岀媯鐘梾鍙戠梾浜烘暟鏈€澶氱殑鍗板害涔熸寮忓甯冨皢鍦ㄥ崄骞村唴娑堢伃鐙傜姮鐥呫€傛嵁鎮夛紝涓浗鍗敓閮ㄧ洰鍓嶄篃姝ｅ湪閰濋吙鍒跺畾涓浗鐨勩€婄媯鐘梾闃叉不瑙勫垝銆嬶紝浼拌涓浗涔熷皢鍔涗簤鍦ㄥ崄骞村唴娑堢伃鐙傜姮鐥?/span>[18]銆傚瀹跺吇鍔ㄧ墿锛堢姮銆佺尗绛夛級鍙婁笌浜烘帴瑙︾浉瀵硅緝涓哄瘑鍒囩殑閲庣敓鍔ㄧ墿閲囧彇鏈夋晥鐨勫厤鐤帾鏂斤紝杩欎笉浣嗘槸棰勯槻浜虹媯鐘梾鏈€鏈夋晥鐨勬帾鏂斤紝涔熸槸娆х編绛夊彂杈惧浗瀹舵帶鍒剁媯鐘梾鎴愬姛鐨勭粡楠岋紝杩欏皢瀵归檷浣庢垜鍥界殑鐙傜姮鐥呭彂鐥呯巼鍙婃湁鏁堟帶鍒剁敋鑷冲疄鐜版秷鐏媯鐘梾鐨勭洰鏍囪捣鍒板喅瀹氭€х殑浣滅敤銆?/span>
鐩墠浣跨敤鐨勭媯鐘梾鐤嫍鏄伃娲荤柅鑻楋紝闇€瑕佸湪28d澶╁唴娉ㄥ皠5閽堬紙鍏朵腑鏈夊緢澶т竴閮ㄥ垎杩橀渶瑕佹敞灏勭媯鐘梾鍏嶇柅鐞冭泲鐧斤級锛屾棦楹荤儲鍙堣垂閽便€傚挨鍏舵槸鍦ㄤ竴浜涘彂灞曚腑鍥藉锛屼汉浠鐙楀挰浼ゅ悗鐢变簬缁忔祹鎴栨椂闂村師鍥狅紝鏍规湰鏃犳硶鍧氭寔鎵撳畬鐤嫍锛屾渶缁堝鑷寸梾鍙戞浜°€傝€屾柊鍨嬬媯鐘梾鐤嫍锛屾敞灏勪竴閽堝嵆瓒充互鎻愪緵鍏呭垎鐨勫厤鐤繚鎶わ紝璇ョ柅鑻楀皢鏈夊姪浜庢棭鏃ュ湪鍙戝睍涓浗瀹跺疄鐜板熀鏈秷鐏媯鐘梾鐨勭洰鏍囥€?/span>
鐙傜姮鐥呯梾姣掔殑鍙嶅悜閬椾紶瀛︽妧鏈负鎴戜滑鎻愪緵浜嗗紑鍙戞柊涓€浠ｇ媯鐘梾鐤嫍鐨勫彲鑳芥€с€備綔涓轰竴绉嶉拡瀵逛汉鍏藉叡鎮ｇ梾鐨勭柅鑻楋紝璇ョ柅鑻楀彲棣栧厛寮€鍙戜负鍏界敤鐤嫍銆傚湪鍏界敤鐤嫍鍟嗕笟鍖栨帹骞垮簲鐢ㄧ殑鍚屾椂锛屽彲鑳界Н绱ぇ閲忔湁浠峰€肩殑璧勬枡锛屼互渚胯繘涓€姝ョ‘璁よ繖浜涚粡鍩哄洜鏀归€犵殑鐙傜姮鐥呭噺姣掓椿鐤嫍鏄惁鍏锋湁瓒冲鐨勪綔涓轰汉鐢ㄧ柅鑻楃殑娼滆川锛?/span>浠庤€屽彲鑳藉湪涓嶄箙鐨勫皢鏉ヤ负浜虹敤鐙傜姮鐥呯柅鑻楁彁渚涗竴绉嶅粔浠峰拰浣跨敤绠€渚跨殑鏇夸唬鍝?span style="mso-bidi-font-weight: bold">銆?/span>
鍙傝€冩枃鐚?/span>
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锛堟敹绋挎棩鏈燂細2009锛?/span>12锛?/span>10锛?/span>
