本文選題：靜脈局部麻醉 + 大鼠　； 參考：《四川大學(xué)》2007年碩士論文

【摘要】： 背景： 靜脈局部麻醉(Intravenous regional anesthesia；IVRA)，又稱Bier Block，于1908年開始應(yīng)用于臨床。此種方法主要適用于成人的四肢短小手術(shù)，具有經(jīng)濟、簡便、效果確切、無神經(jīng)創(chuàng)傷等優(yōu)點，現(xiàn)歐美等國家仍廣泛應(yīng)用。目前報道應(yīng)用于IVRA研究的動物模型有狗和兔子等，但此類模型價格昂貴、操作復(fù)雜、重復(fù)性差，因此需要建立新的經(jīng)濟實用的動物模型。 阿米替林是一種傳統(tǒng)的三環(huán)類抗抑郁藥，主要經(jīng)全身用藥治療抑郁癥、緩解神經(jīng)病理性疼痛等。最近動物實驗研究發(fā)現(xiàn)阿米替林可以產(chǎn)生與傳統(tǒng)局麻藥類似的神經(jīng)阻滯作用。本研究旨在建立大鼠IVRA模型，利用該模型研究阿米替林的IVRA效能、作用時間、局部應(yīng)用毒性、安全范圍等，探討阿米替林在IVRA中應(yīng)用的可能性，為臨床應(yīng)用提供理論及實驗基礎(chǔ)。 第一部分大鼠IVRA模型的建立 目的： (1)建立大鼠IVRA模型(2)驗證大鼠IVRA模型中藥物擴散(3)觀察模型中止血帶阻斷時間對鼠尾神經(jīng)功能影響。 方法： (1)健康成年雄性SD大鼠16只，隨機均分為0.5％利多卡因?qū)嶒灲M和生理鹽水對照組。將鼠尾均分成三段，即上段、中段、末段。進行鼠尾靜脈穿刺、驅(qū)血、固定止血帶(鼠尾上段、中段交界處)、注藥等操作建立大鼠IVRA模型。以夾尾反應(yīng)陰性(夾尾無逃避等反應(yīng))做為鼠尾局部麻醉作用的有效指標(biāo)，以甩尾反應(yīng)時間(Tail-Flick Latency，TFL)恢復(fù)至1—4秒基礎(chǔ)范圍內(nèi)為鼠尾感覺神經(jīng)恢復(fù)的判斷指標(biāo)。觀察并記錄給藥后鼠尾各段夾尾反應(yīng)、TFL以及松止血帶后夾尾反應(yīng)、甩尾反應(yīng)的恢復(fù)時間，并于第二日觀察TFL及鼠尾皮膚情況。 (2)健康成年雄性大鼠3只，如實驗第(1)建立大鼠IVRA模型，給予美藍(lán)0.5ml。通過觀察給藥后鼠尾皮膚顏色變化，驗證模型中藥物的擴散。 (3)健康成年雄性大鼠24只，隨機均分為四組：止血帶阻斷時間為10分鐘組(S_(10)組)，15分鐘組(S_(15)組)，30分鐘組(S_(30)組)，60分鐘組(S_(60)組)。如實驗(1)建立大鼠IVRA模型，給予生理鹽水0.5ml，四組分別留置不同時間的止血帶。觀察給予鹽水后及松止血帶前1分鐘夾尾反應(yīng)，松止血帶后第1、5、10、20、30、60分鐘、第二日的TFL及第二日的鼠尾皮膚情況。 結(jié)果： (1)利多卡因組：大鼠給藥后僅產(chǎn)生鼠尾中、末段(止血帶以下)的夾尾反應(yīng)陰性，且TFL為10秒。松止血帶后鼠尾中段、末段夾尾反應(yīng)恢復(fù)時間分別為17.5±11.2分鐘，26.4±19.6分鐘，；TFL恢復(fù)時間分別為30.3±20.5分鐘，41.5±29.4分鐘。鼠尾中、末段恢復(fù)時間比較均有統(tǒng)計學(xué)差異(P＜0.05)。生理鹽水組：大鼠給藥后鼠尾中、末段夾尾反應(yīng)陽性，各時點TFL均＜4秒，TFL和基礎(chǔ)值無統(tǒng)計學(xué)差異(P＞0.05)。兩組鼠尾上段夾尾反應(yīng)陽性，各時點TFL均＜4秒，和基礎(chǔ)值比較無統(tǒng)計學(xué)差異(P＞0.05)。兩組大鼠第二日鼠尾各段TFL和基礎(chǔ)值比較均無統(tǒng)計學(xué)差異，鼠尾皮膚完好。 (2)3只大鼠給藥后僅止血帶以下的鼠尾皮膚變?yōu)樗{(lán)黑色。 (3)四個不同止血帶時間組，大鼠給予生理鹽水后夾尾反應(yīng)均為陽性；松止血帶后僅S_(60)組鼠尾中、末段第1分鐘TFL＞4秒，和基礎(chǔ)值比較有統(tǒng)計學(xué)差異(P＜0.05)。其余各組各時間點TFL和基礎(chǔ)值比較均無統(tǒng)計學(xué)差異(P＞0.05)。大鼠第二日各組鼠尾各段TFL和基礎(chǔ)值比較均無統(tǒng)計學(xué)差異，鼠尾皮膚完好。 結(jié)論： 大鼠IVRA簡單易行，經(jīng)濟實用，成功率高，具有臨床IVRA特點，可以用作IVRA的藥物相關(guān)研究等。 第二部分阿米替林、布比卡因及利多卡因IVRA效能的比較 目的： 本實驗采用序貫法研究阿米替林IVRA作用的半數(shù)有效濃度(EC_(50))，并和傳統(tǒng)的局麻藥布比卡因、利多卡因比較，探討阿米替林的IVRA麻醉效能。 方法： 體重為190—240克的健康成年雄性大鼠90只，隨機均分為阿米替林組、布比卡因組及利多卡因組。建立大鼠IVRA模型，以鼠尾中段夾尾反應(yīng)陰性作為鼠尾局部麻醉作用的判斷指標(biāo)，以序貫法分別求出三種藥物的EC_(50)值，直到實驗中出現(xiàn)有效到無效6個交叉點時終止實驗。計算EC_(50)值及藥物效價比。 結(jié)果： 阿米替林、布比卡因及利多卡因的IVRA作用EC_(50)分別為0.11％、0.06％及0.13％。阿米替林和布比卡因的效價比為0.54(95％CI，0.38-0.71)，阿米替林和利多卡因的效價比為1.18(95％CI，1.52-0.84)。布比卡因和利多卡因的效價比為0.46(95％CI，0.31-0.61)。 結(jié)論： 大鼠IVRA模型可用作藥物IVRA效能的測定。阿米替林IVRA效能高于利多卡因，效價比為1.18(95％CI，1.52-0.84)；低于布比卡因，效價比為0.54(95％CI，0.38-0.71)。 第三部分阿米替林、布比卡因局部麻醉作用持續(xù)時間及局部組織毒性的比較 目的： 通過和等效濃度的布比卡因比較，探討阿米替林局部麻醉作用持續(xù)時間和局部組織毒性。 方法： 體重為190—240克的健康成年雄性大鼠32只，隨機分為四組，即藥物等效濃度實驗組：0.22％阿米替林組(A_(2EC50)組，n=8)、0.33％阿米替林組(A_(3EC50)組，n=8)、0.12％布比卡因組(B_(2EC50)組，，n=8)，0.18％布比卡因組(B_(3EC50)組，n=8)。建立大鼠IVRA模型，各組分別給予0.22％阿米替林0.5ml、0.33％阿米替林0.5ml、0.12％布比卡因0.5ml、0.18％布比卡因0.5ml。觀察實驗當(dāng)日局部麻醉作用、神經(jīng)功能恢復(fù)時間，并于第二、五、九日進行夾尾反應(yīng)、TFL測量及鼠尾大體皮膚組織評分。 結(jié)果： B_(2EC50)組、B_(3EC50)組局部麻醉作用恢復(fù)時間分別為38.7±16.8分鐘、51.3±17.7分鐘；A_(2EC50)組及A_(3EC50)組局部麻醉作用恢復(fù)時間分別為232.5±96.4分鐘和380.0±127.9分鐘，顯著長于布比卡因組(P＜0.001)，約為同等效濃度布比卡因的6—7倍。第二、五、九日A_(2EC50)組及B_(2EC50)組、B_(3EC50)組及A_(3EC50)組的5只大鼠：大鼠各段夾尾反應(yīng)陽性，TFL均在1—4秒內(nèi)，和基礎(chǔ)值比較均無統(tǒng)計學(xué)差異(P＞0.05)；鼠尾皮膚完好，皮膚評分為0分。A_(3EC50)組另外3只大鼠夾尾反應(yīng)和TFL未恢復(fù)；皮膚損傷，皮膚評分為6分。 結(jié)論： 1．阿米替林局部麻醉作用時間長，為同等效濃度布比卡因長的6—7倍。 2．阿米替林組織毒性與濃度相關(guān)，0.33％可產(chǎn)生局部神經(jīng)損傷。 小結(jié) 本研究(1)利用大鼠鼠尾特點，建立新的IVRA模型。應(yīng)用夾尾反應(yīng)作為鼠尾局部麻醉作用的判斷指標(biāo)，應(yīng)用甩尾時間作為鼠尾神經(jīng)功能恢復(fù)的評價指標(biāo)。大鼠IVRA模型中，通過給予美藍(lán)試劑，證明藥物可以通過滲透至止血帶以下皮膚組織；通過給予利多卡因，證明局麻藥可以產(chǎn)生止血帶以下的局部麻醉作用；止血帶阻斷60分鐘未造成鼠尾神經(jīng)不可逆損傷，阻斷30分鐘未影響松止血帶后的TFL。新建的大鼠IVRA模型有以下優(yōu)點：①具有臨床IVRA的基本特點。②評價指標(biāo)明確③模型成功率高④簡單經(jīng)濟⑤可重復(fù)性強等。(2)利用大鼠IVRA模型，采用序貫法得出阿米替林、布比卡因及利多卡因IVRA作用的EC_(50)分別為0.11％、0.06％及0.13％。阿米替林與兩種傳統(tǒng)的局麻藥效價比分別為0.54(95％CI，0.38-0.71)和1.18(95％CI，1.52-0.84)。(3)大鼠IVRA模型中，等效濃度的阿米替林麻醉作用恢復(fù)時間顯著長于布比卡因(P＜0.001)，約為布比卡因的6-7倍。0.33％阿米替林組3只大鼠出現(xiàn)TFL未恢復(fù)，鼠尾皮膚組織損傷，說明①阿米替林和布比卡因相比，雖然IVRA效能較低，但一旦達到有效濃度后，其產(chǎn)生神經(jīng)阻滯時間明顯長于同等效濃度甚至更高濃度的布比卡因。②阿米替林存在濃度相關(guān)的局部組織毒性等，0.33％可產(chǎn)生局部組織損傷。綜上所述，大鼠IVRA模型簡單易行，經(jīng)濟實用，成功率高，可以用作IVRA的藥物相關(guān)研究等。根據(jù)阿米替林作用時間長、效能低、高濃度會產(chǎn)生局部組織毒性的特點，探討阿米替林和傳統(tǒng)的局麻藥合用或作為局麻藥的輔助藥發(fā)揮其超長效神經(jīng)阻滯作用等具有重要意義。
[Abstract]:Background :





Intravenous regional anesthesia
IVRA , also known as Bier Block , began to be used in clinic in 1908 . This method is mainly applicable to adult limb short - term operation , has the advantages of economy , convenience , exact effect , no nerve trauma , etc . It is widely used in animal models such as dogs and rabbits . However , the models are expensive , complex in operation and poor in repeatability . Therefore , it is necessary to establish a new economic and practical animal model .





Amidlin is a kind of traditional tricyclic antidepressants . It is mainly used for treating depression and relieving neuropathic pain . Recently , it has been found that amitripin can produce nerve block similar to traditional Chinese medicine . This study aims to establish the rat IVRA model , and use the model to study the IVRA efficacy , the action time , the local application toxicity , the safety range and so on . The possibility of the application of amitriptimibe in IVRA is discussed , and the theory and experimental basis for clinical application are provided .





The establishment of the IVRA model in the first part of rats





Purpose :





( 1 ) To establish the rat IVRA model ( 2 ) to verify the effect of tourniquet blocking time on the rat tail neurological function in the rat IVRA model .





Method :





( 1 ) Sixteen healthy adult male SD rats were randomly divided into 0.5 % lidocaine group and normal saline control group . The rats were divided into three segments : upper segment , middle segment and last segment .





( 2 ) The rat IVRA model was established in 3 healthy adult male rats ( 1 ) , and 0.5 ml of methylene blue was given . After observation of the color change of the tail skin of rats , the diffusion of the drug in the model was verified .





( 3 ) Twenty - four healthy male rats were randomly divided into four groups : group S _ ( 10 ) , 15 - minute group ( S _ ( 15 ) group ) , 30 - minute group ( S _ ( 30 ) group ) and 60 - minute group ( S _ ( 60 ) group ) .





Results :





( 1 ) In the lidocaine group , only the tail of the rat tail was produced after the administration of the rats , the tail end ( below the tourniquet ) was negative , and the TFL was 10 seconds . The recovery time of the tail of the tail of the tail was 17.5 鹵 11.2 min , 26 . 4 鹵 19.6 min , respectively .
The recovery time of TFL was 30 . 3 鹵 20 . 5 min , 41 . 5 鹵 29 . 4 min .





( 2 ) After administration of 3 rats , only the tail skin of the mouse tail below the tourniquet became blue - black .





( 3 ) After four different tourniquet time groups , the tail reaction was positive after the rats were given physiological saline .
There was no statistical difference between the TFL and the basal values in the other groups ( P > 0.05 ) . There was no statistical difference between the TFL and the basal values at the second day of the rats , and the tail skin was intact .





Conclusion :





IVRA in rats is simple , economical , practical and has high success rate . It has the characteristics of IVRA and can be used as a drug - related study of IVRA .





Comparison of the efficacy of the second part of Amidin , bupivacaine and lidocaine IVRA





Purpose :





In this experiment , the effective concentration ( EC _ ( 50 )) of IVRA was studied by sequential method , and compared with traditional local anesthetic bupivacaine and lidocaine , the efficacy of IVRA in amitripis was discussed .





Method :





Ninety - four healthy adult male rats weighing 190 - 240 g were randomly divided into amitriplin group , bupivacaine group and lidocaine group . The model of IVRA was established . The EC _ ( 50 ) value of three drugs was determined by sequential method . The EC _ ( 50 ) value and the drug effect ratio were calculated .





Results :





The potency ratio of amitriplocillin , bupivacaine and lidocaine was 0.11 % , 0.06 % and 0.13 % , respectively . The potency ratio of amitripinide and bupivacaine was 0.54 ( 95 % CI , 0.38 - 0.71 ) , and the potency ratio of amitriplocillin and lidocaine was 1.18 ( 95 % CI , 1.52 - 0.84 ) . The potency ratio of bupivacaine and lidocaine was 0.46 ( 95 % CI , 0.31 - 0.61 ) .





Conclusion :





The IVRA model could be used as the efficacy of IVRA in rats . The efficacy of amitripinidine IVRA was higher than that of lidocaine and the potency ratio was 1.18 ( 95 % CI , 1.52 - 0.84 ) ;
Below bupivacaine , the potency ratio was 0.54 ( 95 % CI , 0.38 - 0.71 ) .





Comparison of the duration of local anesthesia and local tissue toxicity in the third part of amitripin and bupivacaine





Purpose :





The duration of local anesthesia and local tissue toxicity of amitriplocillin were investigated by comparison with bupivacaine in the equivalent concentration .





Method :





Thirty - two healthy adult male rats weighing 190 - 240 g were randomly divided into four groups : group A _ ( 2 _ 50 ) , n = 8 ) , 0 . 33 % ( group A _ ( 3 EC50 ) group , n = 8 ) , 0 . 12 % bupivacaine group ( group B _ ( 2 EC50 ) , n = 8 ) , 0 . 18 % bupivacaine group ( group B _ ( 3 EC50 ) , n = 8 ) . A rat IVRA model was established , and the rats were given 0 . 22 % Amidlin 0.5 ml , 0 . 33 % amoeteine 0.5 ml , 0 . 12 % bupivacaine 0.5 ml , 0 . 18 % bupivacaine 0.5 ml . observe the local anesthetic effect on the day of the experiment , the nerve function recovery time , and the second , fifth and ninth day carry on the tail reaction , the TFL measurement and the rat tail gross skin tissue score .





Results :





The recovery time of local anesthesia in group B _ ( 2EC50 ) group and B _ ( 3EC50 ) group was 38.7 鹵 16.8 minutes , 51.3 鹵 17.7 min , respectively .
The recovery time of local anesthesia in A _ ( 2EC50 ) group and A _ ( 3EC50 ) group was 232.5 鹵 96.4 minutes and 38.0 鹵 127.9 minutes , respectively , which was significantly longer than that of bupivacaine group ( P < 0.001 ) , which was about 6 - 7 times of the same equivalent concentration bupivacaine . The second , fifth , nine - day A _ ( 2EC50 ) group and B _ ( 2EC50 ) group , B _ ( 3EC50 ) group , and A _ ( 3EC50 ) group had no statistical difference ( P > 0.05 ) .
The skin was intact and the skin score was 0 . The other 3 rats in the A _ ( 3 EC50 ) group did not recover from the tail reaction and TFL .
Skin injury , skin score of 6 points .





Conclusion :





1 . The local anesthetic duration of amitripin is 6 - 7 times longer than that of bupivacaine .





2 . The toxicity and concentration of amitrip盲lin were correlated , 0.33 % could result in local nerve injury .





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In this study , a new IVRA model was established by using tail - tail characteristics of rats . The tail - tail reaction was used as the index to evaluate the local anesthetic effect of rat tail . The tail - tail time was used as the evaluation index for the recovery of rat tail nerve function .
By administering lidocaine , it is shown that the local anesthetic effect of the local anesthetic can be produced by the local anesthetic .
The results showed that the recovery time of IVRA in rats was significantly longer than that of bupivacaine ( P & lt ; 0.001 ) .
【學(xué)位授予單位】：四川大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R614;R-332

【參考文獻】

相關(guān)期刊論文 前1條

1 周素鳳,申彪,祁英杰,霍展樣;大鼠尾部動靜脈血管的觀察[J];新鄉(xiāng)醫(yī)學(xué)院學(xué)報;1999年01期

本文編號：1986602