【作者】 罗钢；

【导师】 杨思进；

【作者基本信息】 泸州医学院 ， 中西医结合临床， 2008， 硕士

【摘要】 目的:蛭龙活血通瘀胶囊治疗急性脑梗塞有效性及安全性临床研究,并初步探讨其对大鼠缺血再灌注脑梗塞区神经细胞凋亡的影响。方法:1临床部分采用随机、对照、平行试验研究。将符合纳入标准的研究对象按随机数字表1:1随机分入观察组和对照组进行研究。符合病例选择标准共计60例,其中观察组30例,对照组30例。中医诊断、分型标准参照《中药新药治疗中风病的临床研究指导原则》的标准。西医诊断标准参照1995年第4次全国脑血管病学术会议修订的“各类脑血管疾病诊断要点”中有关脑梗死的诊断标准。中医辨证属中风中经络型中的风痰瘀阻型。观察组采用基础治疗加蛭龙活血通瘀胶囊4粒tid,对照组采用基础治疗,2周为一疗程。观察中医证候、中国脑卒中临床神经功能缺损评分(CSS)、美国国立卫生研究院卒中量表(NIHSS)评分、日常生活活动能力量表Barthel指数(BI)评分、实际完成日常生活活动的量表改良Rankin量表(MRS)评分、血脂、血液流变学、血管内皮细胞分泌功能检测及药物安全性监测。2实验部分采用线拴法建立大鼠局灶性脑缺血再灌注损伤模型,将40只雄性SD大鼠随机分为观察组(蛭龙活血通瘀胶囊)10例、对照组(步长脑心通)10例、模型组10例及假手术组10例,用药7天,应用TUNEL法和免疫组织化学法检测各组大鼠脑组织凋亡细胞的分布及bcl-2、Caspase3蛋白的表达。结果:1临床研究(1)治疗后观察组总有效率93.33%,对照组总有效率76.67%,两组有着显著差异(P<0.01);治疗后两组CSS、NIHSS、BI、MRS评分均有不同程度改善,观察组CSS及BI两项评分改善较对照组更为显著(P<0.05);观察组治疗后肢体麻木、口舌歪斜、头晕目眩、痰多而粘、舌象均有明显改善(P<0.01),对照组仅肢体麻木、头晕目眩、脉象三项有所改善(P<0.05),且观察组在改善各症状优于对照组(P<0.05)。(2)治疗后观察组TC、TG和LDL-C显著降低(p<0.01),且疗效显著优于对照组(p<0.05);观察组全血粘度(高切、低切值)、红细胞聚集指数、血沉、血小板聚集率和纤维蛋白原明显下降(p<0.01),疗效显著优于对照组(p<0.01);两组经治疗后血管内皮细胞分泌功能检测指标都有不同程度改善,观察组内皮素(ET)、血栓烷B2(TXB2)、纤溶酶原激活剂抑制物-1(PAI-1)显著降低,并使ET/NO比值显著降低,tPA/PAI比值显著增高(P<0.05,P<0.01),而对照组在ET、6-酮-前列腺素F1a(6-keto-PGF1α)、组织纤溶酶原激活物(tPA)和PAI-1有所改善,但观察组ET,PAI改善较对照组更为明显(P<0.01)。(3)整个观察过程中未发现明显不良事件。2动物实验(1)实验证实了急性脑梗塞缺血再灌注损伤凋亡细胞的存在,模型组脑神经细胞凋亡数量显著高于假手术组(P<0.01),蛭龙活血通瘀组与步长脑心通药物干预组与模型组相比细胞凋亡指数显著下降(P<0.01),但蛭龙活血通瘀组与步长脑心通药物干预组二者比较无明显差异(P>0.05)。(2)免疫组化法检测细胞凋亡基因bcl-2及Caspase3蛋白表达的表达。模型组脑神经细胞bc1-2和Caspase-3基因蛋白表达均显著高于假手术组(P<0.01),与模型组相比,蛭龙活血通瘀组与脑心通组明显上调bc1-2的基因表达(P<0.01),明显抑制Caspase-3基因蛋白表达(P<0.01),蛭龙活血通瘀组与步长脑心通药物干预组间比较无明显差异(P>0.05)。结论:1蛭龙活血通瘀胶囊治疗急性脑梗塞疗效较为满意,能有效改善神经功能缺损评分、中医证候疗效,降低血脂、改善血液流变学指标和改善血管内皮分泌功能失调。2蛭龙活血通瘀胶囊对急性脑梗塞引起的神经细胞凋亡有明显抑制作用。其机制可能与上调bcl-2,抑制Caspase-3有关。更多还原

【Abstract】 Objective: Zhilong Huoxue Tongyu capsule on the treatment of patients with acute cerebral infarction efficacy and safety of clinical research, and to explore their areas of rat cerebral infarction cell apoptosis.Methods: 1 Part of a Clinical: A randomized, controlled ,Parallel,trial study. Into the standard will be consistent with the object of study by a random number table: a randomized into the treatment group and the control group were studied. Case selection criteria with a total of 60 cases, of which 30 treatment group, the control group of 30 patients. TCM diagnosis, classification criterion-referenced "new Chinese medicine treatment of stroke clinical study of the guiding principles of standards". Western medicine diagnostic criterion-referenced 1995 4th National Conference cerebrovascular disease revised "various cerebrovascular disease diagnosis of cerebral infarction" in the diagnostic criteria. TCM Meridian is a type of stroke in the wind phlegm Yuzu-treatment group based therapy plus a Zhilong Huoxue Tongyu capsule four tid, and the control group used for the basis, for a two week course. Observation security, Syndrome, neurological impairment score, stroke Scale (NIHSS) score, ADL Scale Barthel Index (BI) score, the actual completion of the activities of daily living scale modified Rankin scale (MRS) score, serum lipids, blood rheology, vascular endothelial cell function testing.2 Part of Experimental:Rat model of focal cerebral ischemia, 40 male SD rats were randomly divided into Zhilong Huoxue Tongyu capsule Observer Group 10 cases, step Naoxintong positive control group and 10 cases, the model group 10 and 10 cases of sham-operated group, 7-day drug application TUNEL method and immunohistochemical detection of the rat brain and the distribution of apoptotic bcl-2, Caspase3 immunoreactive cells observation.Results: 1 Clinical results show that: After treatment observation group, the total efficiency of 93.33% in control group, the total efficiency of 76.67%, compared with the significant differences (P<0.01) after treatment groups CSS, NIHSS, BI, in varying degrees MRS score improvement Observer Group CSS and BI score improved significantly more than the control group (P<0.05) observed before and after treatment numbness, and awaking askew, dizziness dizzying, and visco-Tan Zhi, tongue and have significantly improved (P<0.01), the control group only numbness, dizziness dizzying, pulse 3 has improved (P <0.05), and the Observer Group in improving symptoms than the control group (P<0.05); Observer Group to reduce TC, TG, LDL-C, treatment and there is significant difference (P<0.01), and compared with the control group there were significant differences (P<0.05); Observer Group whole blood viscosity (high and low shear value), erythrocyte aggregation index, ESR and platelet aggregation and fibrinogen decreased significantly (P<0.01), and compared with the control group there were significant differences (P<0.01), vascular endothelial cell function testing of the two groups after treatment indicators have improved to varying degrees, Observer Group to endothelin (ET), thromboxane B2 (TXB2), plasminogen activator inhibitor-1 (PAI-1) was significantly reduced, and ET / NO ratio was significantly decreased, and TPA / PAI ratio was significantly higher (P<0.05,P<0.01), while the control group in ET, 6-F1a prostaglandin (6-keto-PGF1α), tissue plasminogen activator (TPA), PAI-1 had improved, but improved compared with the control group more obvious group (P<0.01) in the entire process of observation found no significant adverse events.2 The experimental results show that: Through DNA nick end labeling (TUNEL) confirmed acute cerebral ischemia and reperfusion in the presence of apoptotic cells. Model group neuronal apoptosis was significantly higher than the number of sham-operated group, Huoxue Tongyu group and Naoxintong drug intervention group compared with the model group apoptosis index decreased significantly (P<0.01), indicating Zhilong Huoxue Tongyu capsule and Step long Naoxintong capsule on the brain cells inhibit apoptosis. Immunohistochemistry was used to detect apoptosis gene bcl-2 protein expression and Caspase3 changes. Model group brain cells bc1-2 and Caspase-3 gene expression were significantly higher than the sham-operated group (P<0.01), compared with the model group, Huoxue Tongyu Naoxintong group and the group can enhance bc1-2 gene expression (P< 0.01) significantly inhibited Caspase-3 gene expression (P <0.01).Concusion: 1 Zhilong Huoxue Tongyu capsule treatment of patients with acute cerebral infarction more satisfied with the improvement of neurologic impairment score Syndrome effective than the control group, the main symptom improvement is better than the control group, serum lipid lowering efficacy superior to the control group, improving hemorrheology Indexes, effective than the control group, reversed secretion of vascular endothelial dysfunction, better than the control group. 2 cerebral infarction and neural cell apoptosis, Zhilong Huoxue Tongyu capsule on the treatment of acute cerebral ischemia may be inhibited by injury at the same time block Caspase-3 activation and inhibition of apoptosis alleviate neuronal apoptosis.更多还原