辛伐他汀对大鼠蛛网膜下腔出血后脑血管痉挛的治疗效果研究
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摘要
目的:观察辛伐他汀对大鼠蛛网膜下腔出血后脑血管痉挛的治疗效果并探讨其可能机制。方法:将48只健康Wistar大鼠随机分为正常对照组、模型组、辛伐他汀组,每组各16只。模型组以及辛伐他汀组给予枕大池注入自体动脉血法以建立大鼠蛛网膜下腔出血后脑血管痉挛的动物模型,辛伐他汀组于第1次注血后开始给予辛伐他汀皮下注射,其余两组给予等体积生理盐水皮下注射。比较各组大鼠情况、组织学检查结果、蛛网膜下腔出血量评分、神经功能缺损评分、血管内径、血管舒张度、血管痉挛程度、eNOS以及TNF-α蛋白表达水平。结果:实验过程中,正常对照组无大鼠死亡,模型组大鼠死亡率为33.33%,辛伐他汀死亡率为6.67%,较模型组显著降低(P<0.05)。治疗后,与正常对照组相比,模型组及辛伐他汀组大鼠蛛网膜下腔出血量评分及TNF-α阳性表达率较高(P<0.05),神经功能缺损评分、血管内径、D/T及eNOS阳性表达率较低(P<0.05);与模型组相比,辛伐他汀组蛛网膜下腔出血量评分及TNF-α阳性表达率较低(P<0.05),神经功能缺损评分、血管内径、D/T及eNOS阳性表达率较高(P<0.05)。结论:辛伐他汀可有效改善蛛网膜下腔出血后脑血管痉挛,这可能与其上调eNOS蛋白表达并下调TNF-α蛋白表达有关。
Objective: To observe the efficacy of simvastatin on the treatment of cerebral vasospasm after subarachnoid hemorrhage in rats. Methods: 48 healthy WISTAR rats were divided into normal control group, model control group and simvastatin group,with 16 rats in each group. The rats in the model control group and model control group were given intracisternal injection of autologous arterial blood to establish the rat animal model of cerebral vasospasm after subarachnoid hemorrhage, and the rats in the simvastatin group were given simvastatin after the first injection of blood, while the other two groups were given saline subcutaneous injection. Then the rats situations, histological examination results, subarachnoid haemorrhage amount grade score, neural function defect score, blood vessel diameter, blood vessels tension degree, vasospasm degree, eNOS and TNF-α protein expression levels of the three groups were observed and compared. Results: In the experiment, there was no death in the normal control group, there were five rats died in the model control group with the death rate of 33.33%, and there was a rat died in the simvastatin group with the death rate of 6.67%. After treatment, compared with the normal control group, the subarachnoid haemorrhage amount score were higher in the model control group and simvastatin group(P<0.05), and neural function defect score, blood vessel diameter and D/T were lower(P<0.05); Compared with model control group, the subarachnoid haemorrhage amount score was lower in the simvastatin group(P<0.05), and neural function defect scale,blood vessel diameter and D/T were higher(P<0.05). Compared with normal control group, eNOS positive expression rate in the model control group and simvastatin group were lower(P<0.05), and the TNF-α positive expression rate was higher(P<0.05); Compared with model control group, the eNOS positive expression rate was higher in the simvastatin group(P<0.05), and the TNF-α positive expression rate was lower(P<0.05). Conclusions: Simvastatin in the treatment of subarachnoid hemorrhage is safe and effective, which can increase the eNOS protein expression, decrease the TNF-α protein expression, reduce the incidence rate of ischemic neurological dysfunction and blood vessel spasm, and it is expect to provide new methods of intervention for clinical treatment.
Objective: To observe the efficacy of simvastatin on the treatment of cerebral vasospasm after subarachnoid hemorrhage in rats. Methods: 48 healthy WISTAR rats were divided into normal control group, model control group and simvastatin group,with 16 rats in each group. The rats in the model control group and model control group were given intracisternal injection of autologous arterial blood to establish the rat animal model of cerebral vasospasm after subarachnoid hemorrhage, and the rats in the simvastatin group were given simvastatin after the first injection of blood, while the other two groups were given saline subcutaneous injection. Then the rats situations, histological examination results, subarachnoid haemorrhage amount grade score, neural function defect score, blood vessel diameter, blood vessels tension degree, vasospasm degree, eNOS and TNF-α protein expression levels of the three groups were observed and compared. Results: In the experiment, there was no death in the normal control group, there were five rats died in the model control group with the death rate of 33.33%, and there was a rat died in the simvastatin group with the death rate of 6.67%. After treatment, compared with the normal control group, the subarachnoid haemorrhage amount score were higher in the model control group and simvastatin group(P<0.05), and neural function defect score, blood vessel diameter and D/T were lower(P<0.05); Compared with model control group, the subarachnoid haemorrhage amount score was lower in the simvastatin group(P<0.05), and neural function defect scale,blood vessel diameter and D/T were higher(P<0.05). Compared with normal control group, eNOS positive expression rate in the model control group and simvastatin group were lower(P<0.05), and the TNF-α positive expression rate was higher(P<0.05); Compared with model control group, the eNOS positive expression rate was higher in the simvastatin group(P<0.05), and the TNF-α positive expression rate was lower(P<0.05). Conclusions: Simvastatin in the treatment of subarachnoid hemorrhage is safe and effective, which can increase the eNOS protein expression, decrease the TNF-α protein expression, reduce the incidence rate of ischemic neurological dysfunction and blood vessel spasm, and it is expect to provide new methods of intervention for clinical treatment.
引文
[1]Kondziella D,Friberg C K,Wellwood I,et al.Continuous EEG monitoring in aneurysmal subarachnoid hemorrhage:A systematic review[J].Neurocritical care,2015,22(3):450-461
[2]Vergouwen M D I,Jong-Tjien-Fa A V,Algra A,et al.Time trends in causes of death after aneurysmal subarachnoid hemorrhage A hospital-based study[J].Neurology,2016,86(1):59-63
[3]Laban K G,Vergouwen M D I,Dijkhuizen R M,et al.Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage:a systematic review and meta-analysis[J].Journal of Cerebral Blood Flow&Metabolism,2015,35(7):1085-1089
[4]Boukobza M,Crassard I,Bousser M G,et al.Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage:a series of 22 cases[J].Neuroradiology,2016,58(1):11-16
[5]Mees S M D,Algra A,Wong G K C,et al.Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage Individual Patient Data Meta-Analysis[J].Stroke,2015,46(11):3190-3193
[6]Beitzke M,Enzinger C,Wünsch G,et al.Contribution of convexal subarachnoid hemorrhage to disease progression in cerebral amyloid angiopathy[J].Stroke,2015,46(6):1533-1540
[7]Ly J V,Singhal S,Rowe C C,et al.Convexity subarachnoid hemorrhage with Pi B positive PET scans:clinical features and prognosis[J].Journal of Neuroimaging,2015,25(3):420-429
[8]Leclerc J L,Blackburn S,Neal D,et al.Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage[J].Proceedings of the National Academy of Sciences,2015,112(4):1155-1160
[9]Donkelaar C E,Bakker N A,Veeger N J G M,et al.Predictive Factors for Rebleeding After Aneurysmal Subarachnoid Hemorrhage Rebleeding Aneurysmal Subarachnoid Hemorrhage Study[J].Stroke,2015,46(8):2100-2106
[10]Kumar G,Shahripour R B,Harrigan M R.Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage:a systematic review and meta-analysis[J].Journal of neurosurgery,2016,124(5):1257-1264
[11]Wong G K C,Chan D Y C,Siu D Y W,et al.High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage Multicenter Randomized Controlled Double-Blinded Clinical Trial[J].Stroke,2015,46(2):382-388
[12]Fontana J,Moratin J,Ehrlich G,et al.Dynamic autoregulatory response after aneurysmal subarachnoid hemorrhage and its relation to angiographic vasospasm and clinical outcome[J].Neurocritical care,2015,23(3):355-363
[13]Schallner N,Pandit R,Robert Le Blanc III A J T,et al.Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1[J].The Journal of clinical investigation,2015,125(7):2609
[14]Boluijt J,Meijers J C M,Rinkel G J E,et al.Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage:a systematic review[J].Journal of Cerebral Blood Flow&Metabolism,2015,35(5):724-733
[15]Dasenbrock H H,Bartolozzi A R,Gormley W B,et al.Clostridium difficile infection after subarachnoid hemorrhage:a nationwide analysis[J].Neurosurgery,2016,78(3):412-420
[16]De Marchis G M,Pugin D,Meyers E,et al.Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome[J].Neurology,2016,86(3):253-260
[17]Fok A,Chandra R V,Gutman M,et al.Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage After Lumboperitoneal Shunt for Fulminant Idiopathic Intracranial Hypertension[J].Journal of Neuro-Ophthalmology,2016,36(2):164-166
[18]Kurtz P,Helbok R,Claassen J,et al.The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage[J].Neurocritical care,2016,24(1):118-121
[19]Alexiades N G,Ellis J A,Meyers P M,et al.Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection:is early surgical exploration warranted?[J].Journal of neurointerventional surgery,2016,8(6):e22-e22
[20]Chugh C,Nyirjesy S C,Nawalinski K P,et al.Red blood cell distribution width is associated with poor clinical outcome after subarachnoid hemorrhage:A pilot study[J].Neurocritical care,2015,23(2):217-224
[2]Vergouwen M D I,Jong-Tjien-Fa A V,Algra A,et al.Time trends in causes of death after aneurysmal subarachnoid hemorrhage A hospital-based study[J].Neurology,2016,86(1):59-63
[3]Laban K G,Vergouwen M D I,Dijkhuizen R M,et al.Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage:a systematic review and meta-analysis[J].Journal of Cerebral Blood Flow&Metabolism,2015,35(7):1085-1089
[4]Boukobza M,Crassard I,Bousser M G,et al.Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage:a series of 22 cases[J].Neuroradiology,2016,58(1):11-16
[5]Mees S M D,Algra A,Wong G K C,et al.Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage Individual Patient Data Meta-Analysis[J].Stroke,2015,46(11):3190-3193
[6]Beitzke M,Enzinger C,Wünsch G,et al.Contribution of convexal subarachnoid hemorrhage to disease progression in cerebral amyloid angiopathy[J].Stroke,2015,46(6):1533-1540
[7]Ly J V,Singhal S,Rowe C C,et al.Convexity subarachnoid hemorrhage with Pi B positive PET scans:clinical features and prognosis[J].Journal of Neuroimaging,2015,25(3):420-429
[8]Leclerc J L,Blackburn S,Neal D,et al.Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage[J].Proceedings of the National Academy of Sciences,2015,112(4):1155-1160
[9]Donkelaar C E,Bakker N A,Veeger N J G M,et al.Predictive Factors for Rebleeding After Aneurysmal Subarachnoid Hemorrhage Rebleeding Aneurysmal Subarachnoid Hemorrhage Study[J].Stroke,2015,46(8):2100-2106
[10]Kumar G,Shahripour R B,Harrigan M R.Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage:a systematic review and meta-analysis[J].Journal of neurosurgery,2016,124(5):1257-1264
[11]Wong G K C,Chan D Y C,Siu D Y W,et al.High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage Multicenter Randomized Controlled Double-Blinded Clinical Trial[J].Stroke,2015,46(2):382-388
[12]Fontana J,Moratin J,Ehrlich G,et al.Dynamic autoregulatory response after aneurysmal subarachnoid hemorrhage and its relation to angiographic vasospasm and clinical outcome[J].Neurocritical care,2015,23(3):355-363
[13]Schallner N,Pandit R,Robert Le Blanc III A J T,et al.Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1[J].The Journal of clinical investigation,2015,125(7):2609
[14]Boluijt J,Meijers J C M,Rinkel G J E,et al.Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage:a systematic review[J].Journal of Cerebral Blood Flow&Metabolism,2015,35(5):724-733
[15]Dasenbrock H H,Bartolozzi A R,Gormley W B,et al.Clostridium difficile infection after subarachnoid hemorrhage:a nationwide analysis[J].Neurosurgery,2016,78(3):412-420
[16]De Marchis G M,Pugin D,Meyers E,et al.Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome[J].Neurology,2016,86(3):253-260
[17]Fok A,Chandra R V,Gutman M,et al.Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage After Lumboperitoneal Shunt for Fulminant Idiopathic Intracranial Hypertension[J].Journal of Neuro-Ophthalmology,2016,36(2):164-166
[18]Kurtz P,Helbok R,Claassen J,et al.The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage[J].Neurocritical care,2016,24(1):118-121
[19]Alexiades N G,Ellis J A,Meyers P M,et al.Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection:is early surgical exploration warranted?[J].Journal of neurointerventional surgery,2016,8(6):e22-e22
[20]Chugh C,Nyirjesy S C,Nawalinski K P,et al.Red blood cell distribution width is associated with poor clinical outcome after subarachnoid hemorrhage:A pilot study[J].Neurocritical care,2015,23(2):217-224