Progress on Study of Thrombolysis with Recombinant Tissue Plasminogen Activators for Acute Ischaemic Stroke

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1 , ( ) FDA Progress on Study of Thrombolysis with Recombinant Tissue Plasminogen Activators for Acute Ischaemic Stroke ZHAO Yong-fei 1,2, JIANG Yu-ping 2, XIAO Bao-guo 2 1 Department of Neurology, Huashan Hospital, Fudan University, Shanghai ; 2 Department of Neurology, Jinshan Hospital, Fudan University, Shanghai , China KEY WORDS acute ischaemic stroke; tissue plasminogen activator; thrombolysis ABSTRACT Thrombolysis for acute ischaemic stroke is a key intervention that can reduce disability from stroke. Intravenous thrombolysis with alteplase is the only approved treatment for acute ischaemic stroke by U. S. Food and Drug Administration but has several limitations. Several feasibility studies on the clinical application of recombinant tissue plasminogen activator were carried out in order to improve the efficacy and safety of thrombolytic therapy in recent years. The developing process of thrombolysis with alteplase and other recombinant tissue plasminogen activators for acute ischaemic stroke as well as their pathological and physiological function in the central nervous system were reviewed. activator rt-pa) h rt-pa 3 (National Institute of Neurological Disorders and Stroke NINDS) (recombinant tissue plasminogen 30% (2013) R A, ( 1969-),,, cjcn1993@126.com

2 349 ( ) t-pa t-pa 2 t-pa (tissue-type plasminogen activator t-pa) t-pa t-pa t-pa [2] t-pa t-pa t-pa t-pa t-pa t-pa [3] t-pa NINDS [7] t-pa 3 h t-pa 15% t-pa 3 NINDS (RCT) 4.5 h t-pa t-pa t-pa (alteplase) t-pa (anistreplase) t-pa t-pa t-pa [3,8] rt-pa t-pa t-pa t-pa t-pa t-pa 527 F

3 350 G K1 K2 P 4.5 h F K2 C- 355 Rt-PA t-pa K2 P F G K1 1. rt-pa FDA 10 U 2 min 30 min 4 6 min 10 U 2 min 1995 NINDS 0.9 mg kg mg 10% 60 min NINDS / 3 h 2008 Cronin [9] h FDA [3,12] mrs % 45.2% OR= %CI P<0.05 (2.4%) T103N (0.2%) 90 d N117Q [10] SITS-ISTR min 3 h h 0.9 mg kg -1 [12] 3 PAI-1 mrs 58%( h ) 56.3%( 3 h ) [9,10] 2 3 h 90 min FDA 4.5 h h mg kg h 2. (reteplase) t-pa 4 4 min 15 min 3. (tenecteplase) t-pa 3 KHRRR( )AAAA Haley [13] Liao (2013) h NINDS 4 TIMS-China mg kg h h rt-pa( mg kg -1 ) h 0.5 mg kg d 24 h 90 d NINDS 0.1 mg kg -1 ECASS

4 351 B/ RCT 0.4 mg kg mg kg % µg kg d 14 21% 0.1 mg kg mg kg -1 (5%) (6%) [14] Parsons [15] 0.1 mg kg mg kg -1 B (monteplase) t-pa 24 h CT C84S 90 d T61 N117 (mrs 0 2) min 90 d 28% 10% 0.25 mg kg d 0.1 mg kg -1 [18] 6. (amiteplase) K (desmoteplase) α-1 t- PA K1 30~47 min [19] F β 7. (lanoteplas) t-pa 2.8 h rt-pa F G K1 Hacke [16] N117Q min 3 9 h 30 d 8 h MRI / 20% NIHSS mg µg kg -1 t-pa t-pa MRI 23.1% 46.7% 20% t-pa 1%~3% t-pa 71.4% 90 d 13.3% 46.7% 60% 3~9 h MRI / 90~125 µg kg -1 Hacke [17] >80 2 t-pa t-pa [20] MRI CT 90 µg kg -1 (60 ) 125 µg kg -1 (68 ) (65 ) 1~2 min 90 d [19]

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