蛇毒制剂治疗脑梗死国内外状况
成都军区昆明总医院血栓疾病研究中心 (650223)
当今世界还没有一种治疗脑梗死的特效药物，而诸多药物正在用于治疗急性脑梗死及其恢复期。一些扩张血管的钙离子拮抗剂和抗凝剂如肝素钙，溶栓药：尿激酶，链激酶，rt-pA都有许多深入研究，结论均不一致，大体上认为钙离子拮抗剂在急性发作期，由于扩张血管可加重脑水肿，没有太多好处，在恢复期由于阻滞钙离子沉积在细胞内，可防止细胞死亡，改善脑细胞功能。抗凝剂应用，国外一些联合研究认为有效，与对照组比较有显著差异，但对栓子的清除，不如溶栓药物，但出血的危险性，也对使用溶栓药物增加顾虑。溶栓剂超早期应用可改善早期缺血性瀑布样反应，减少兴奋性氨基酸及自由基大量产生，早期溶栓改善血循、减少神经细胞损害，多数学者认为利多于弊，问题在于：溶栓剂有严格时间窗限制，在中国乃至全球，发病在2-4 h内用此药的病例为数较少，发病超过4 h以上用链激酶出血率超过25%，rt-pA在20%以上，尿激酶亦有6%-12%，尿激酶由于用药后半衰期较短，仅有15-30分，且损伤血管内皮功能，导致再梗塞的复发率为6%-12%，因此：蛇毒制剂就被中国医学界用以治疗急性脑梗死及其恢复期，因为：第一，蛇毒制剂主要作用机理是降低纤维蛋白原，防止血栓进一步加大。第二，有间接的溶栓作用，由于纤溶后形成的大量FDP，可激活体内的纤溶系统、对已形成的纤维蛋白块产生溶解作用，促进形成堵塞的血管再通。第三，时间窗要求不严，不仅超过8 h，甚至超过24 h以后的血栓，也有一定的作用。第四，对高纤维蛋白原症，高血粘症患者有血栓倾向者，可降低纤维蛋白原，降低血粘度，防止血栓产生。第五，对动脉硬化斑块脱落及心源性形成的栓塞效果欠佳，第六，较为安全，经国内大规模、多中心随机双盲对照研究，用药组与对照组比较，脑出血率无增加。中国大陆自1979年至今24年来用蛇毒制剂治疗脑血栓疾病，其中大部分是脑梗死病例，已超过100多万例，是世界上应用蛇毒制剂最多的国家。过去多无双盲随机对照组研究。自1997年起在国家卫生部领导下，脑血管办公室组织两次共计2000多例双盲、随机、对照研究、为时六年，初步认为Defibrase(降纤酶)组可降低神经功能缺损，提高生活质量，出血率不增加，降低复发率，而对死亡率影响不大。
, 百拇医药
The state of therapying cerebral infarction with snake venom
preparation within our country and abroad
YANG Jinghua
Research Center of Cerebral thrombosis Diseases,Kunming General hospital of Chengdu Military Region
Kunming, China 650223
There hasn’t been a specific remedy to treat cerebral infarction at present in the World. Many drugs are using to treat acute cerebral infarction and its restorative stage. Some calcium antagonist and anticoagulant which used in clinic blood vessel dilation such as heparin calcium; drugs to dissolute thrombosis such as urokinase, streptokinase and rt-PA which have been researched deeply. But the conclusions were different . The general recognition is that since blood vessel dilation may add cerebral edema, the application of calcium antagonist in acute attack stage has no good effect. While in restorative stage, calcium are blocked into the cell and deposit in the cells which can prevent the death of cells and improve the function of cerebral cells. The application of anticogulant considered that there is apparent difference with the control group. But its effect to clear the emboli is less than drugs of thrombosis dissolution. It’s danger of bleeding also increases the worrying of application. Ultra-early application of thrombosis dissolution remedy can improve the early stage of ischemic waterfall-like reaction, reduce large number yield of the free radical and excitatory amino acid. Early stage thrombosis dissolution promotes blood circulation and reduce the damage of nerve cells. Most scholars think its advantages are more than disadvantages. The problem is that thrombosis dissolution remedy has strict of time limit. In China and even the whole world, few cases have used the remedy within 2-4 hours of disease attack. The bleeding ratio was over 25% when using streptokinase more than 4 hours of disease attack . Over 20% when using rt-PA, 6%-12 % when using urokinase, The half life period is shorter (only 15-30 minutes), the recurrent rate caused by the damage of blood vessel endothelial function is 6%-12%.
, 百拇医药
Therefore ,snake venom preparation have been used to therapy acute cerebral infarction and It’s restoration stage by Chinese hospitals. 1.The main effective mechanism of snake venom preparation is reducing the fibrinogen and preventing thrombosis further enlarged. 2.Snake venom preparation possesses indirect effect to dissolute thrombosis. Because of lots of FDP produced after fibrinolysis made it can improve the blocked blood vessels passable again. 3. Requirement to time limit is not strict. It is effective to the which formed over 8 hours even 24 hours. 4. For the patients with possible thrombosis caused by hyperplasminemia and high blood viscosity. The snake venom can reduce the fibrinogen and blood viscosity and prevent the thrombosis being formed. 5. It has no good effect to the embolism which were formed by arterioscherotic plaque scaling and cardiogenic diseases. 6. Safer: Through the comparison between therapeutic groups and control groups which have been researched in large scale with polycentric, random double blind comparison in our country, increase of cerebral bleeding have not yet been found: From 1979 up to now,hospitals in the main land of China have therapied the cerebral thrombosis diseases with snake venom preparation for 24 years. More than I million cases have been therapied. Most of them were cerebral infarction. China is the county using snake venom preparation the most. Before 1997, there were no double blind random control group research. Since 1997, under the leadership of Health Ministry, the Office of Cerebrovascular Diseases organized 2 times (more than 2,000 cases ) of double blind random comparative researches and has continued for 6 years. The primitive recognition is that the Defibrase group can reduce defect of Neuro - function, raise vital quality and reduce the recurrence rate while it did not increase the bleeding rate and had no big influence to mortality., 百拇医药(杨靖华)
当今世界还没有一种治疗脑梗死的特效药物，而诸多药物正在用于治疗急性脑梗死及其恢复期。一些扩张血管的钙离子拮抗剂和抗凝剂如肝素钙，溶栓药：尿激酶，链激酶，rt-pA都有许多深入研究，结论均不一致，大体上认为钙离子拮抗剂在急性发作期，由于扩张血管可加重脑水肿，没有太多好处，在恢复期由于阻滞钙离子沉积在细胞内，可防止细胞死亡，改善脑细胞功能。抗凝剂应用，国外一些联合研究认为有效，与对照组比较有显著差异，但对栓子的清除，不如溶栓药物，但出血的危险性，也对使用溶栓药物增加顾虑。溶栓剂超早期应用可改善早期缺血性瀑布样反应，减少兴奋性氨基酸及自由基大量产生，早期溶栓改善血循、减少神经细胞损害，多数学者认为利多于弊，问题在于：溶栓剂有严格时间窗限制，在中国乃至全球，发病在2-4 h内用此药的病例为数较少，发病超过4 h以上用链激酶出血率超过25%，rt-pA在20%以上，尿激酶亦有6%-12%，尿激酶由于用药后半衰期较短，仅有15-30分，且损伤血管内皮功能，导致再梗塞的复发率为6%-12%，因此：蛇毒制剂就被中国医学界用以治疗急性脑梗死及其恢复期，因为：第一，蛇毒制剂主要作用机理是降低纤维蛋白原，防止血栓进一步加大。第二，有间接的溶栓作用，由于纤溶后形成的大量FDP，可激活体内的纤溶系统、对已形成的纤维蛋白块产生溶解作用，促进形成堵塞的血管再通。第三，时间窗要求不严，不仅超过8 h，甚至超过24 h以后的血栓，也有一定的作用。第四，对高纤维蛋白原症，高血粘症患者有血栓倾向者，可降低纤维蛋白原，降低血粘度，防止血栓产生。第五，对动脉硬化斑块脱落及心源性形成的栓塞效果欠佳，第六，较为安全，经国内大规模、多中心随机双盲对照研究，用药组与对照组比较，脑出血率无增加。中国大陆自1979年至今24年来用蛇毒制剂治疗脑血栓疾病，其中大部分是脑梗死病例，已超过100多万例，是世界上应用蛇毒制剂最多的国家。过去多无双盲随机对照组研究。自1997年起在国家卫生部领导下，脑血管办公室组织两次共计2000多例双盲、随机、对照研究、为时六年，初步认为Defibrase(降纤酶)组可降低神经功能缺损，提高生活质量，出血率不增加，降低复发率，而对死亡率影响不大。
, 百拇医药
The state of therapying cerebral infarction with snake venom
preparation within our country and abroad
YANG Jinghua
Research Center of Cerebral thrombosis Diseases,Kunming General hospital of Chengdu Military Region
Kunming, China 650223
There hasn’t been a specific remedy to treat cerebral infarction at present in the World. Many drugs are using to treat acute cerebral infarction and its restorative stage. Some calcium antagonist and anticoagulant which used in clinic blood vessel dilation such as heparin calcium; drugs to dissolute thrombosis such as urokinase, streptokinase and rt-PA which have been researched deeply. But the conclusions were different . The general recognition is that since blood vessel dilation may add cerebral edema, the application of calcium antagonist in acute attack stage has no good effect. While in restorative stage, calcium are blocked into the cell and deposit in the cells which can prevent the death of cells and improve the function of cerebral cells. The application of anticogulant considered that there is apparent difference with the control group. But its effect to clear the emboli is less than drugs of thrombosis dissolution. It’s danger of bleeding also increases the worrying of application. Ultra-early application of thrombosis dissolution remedy can improve the early stage of ischemic waterfall-like reaction, reduce large number yield of the free radical and excitatory amino acid. Early stage thrombosis dissolution promotes blood circulation and reduce the damage of nerve cells. Most scholars think its advantages are more than disadvantages. The problem is that thrombosis dissolution remedy has strict of time limit. In China and even the whole world, few cases have used the remedy within 2-4 hours of disease attack. The bleeding ratio was over 25% when using streptokinase more than 4 hours of disease attack . Over 20% when using rt-PA, 6%-12 % when using urokinase, The half life period is shorter (only 15-30 minutes), the recurrent rate caused by the damage of blood vessel endothelial function is 6%-12%.
, 百拇医药
Therefore ,snake venom preparation have been used to therapy acute cerebral infarction and It’s restoration stage by Chinese hospitals. 1.The main effective mechanism of snake venom preparation is reducing the fibrinogen and preventing thrombosis further enlarged. 2.Snake venom preparation possesses indirect effect to dissolute thrombosis. Because of lots of FDP produced after fibrinolysis made it can improve the blocked blood vessels passable again. 3. Requirement to time limit is not strict. It is effective to the which formed over 8 hours even 24 hours. 4. For the patients with possible thrombosis caused by hyperplasminemia and high blood viscosity. The snake venom can reduce the fibrinogen and blood viscosity and prevent the thrombosis being formed. 5. It has no good effect to the embolism which were formed by arterioscherotic plaque scaling and cardiogenic diseases. 6. Safer: Through the comparison between therapeutic groups and control groups which have been researched in large scale with polycentric, random double blind comparison in our country, increase of cerebral bleeding have not yet been found: From 1979 up to now,hospitals in the main land of China have therapied the cerebral thrombosis diseases with snake venom preparation for 24 years. More than I million cases have been therapied. Most of them were cerebral infarction. China is the county using snake venom preparation the most. Before 1997, there were no double blind random control group research. Since 1997, under the leadership of Health Ministry, the Office of Cerebrovascular Diseases organized 2 times (more than 2,000 cases ) of double blind random comparative researches and has continued for 6 years. The primitive recognition is that the Defibrase group can reduce defect of Neuro - function, raise vital quality and reduce the recurrence rate while it did not increase the bleeding rate and had no big influence to mortality., 百拇医药(杨靖华)