法舒地尔联合阿司匹林治疗椎-基底动脉供血不足疗效观察

目的：评价盐酸法舒地尔联合阿司匹林治疗椎-基底动脉供血不足的临床疗效和安全性。方法：选择符合人选标准的58例椎-基底动脉供血不足患者,随机分为观察组30例与对照组28例,所有患者基础治疗相同。观察组应用法舒地尔60mg静脉滴注,每日1次,联合阿司匹林0．1g每日1次口服,对照组应用丹参25ml静脉滴注,每日1次,联合阿司匹林0．1g每131次口服,14d为1个疗程。观察治疗效果及不良反应。结果：治疗2周后,观察组显效率35．6％,总有效率90％,对照组显效率14．0％,总有效率75．0％,两组比较,差异有统计学意义（P〈0．05）．均未观察到明显不良反应。结论：椎-基底动脉供血不足应用法舒地尔联合阿司匹林,可有效改善临床表现,无严重不良反应。     

法舒地尔联合蚓激酶治疗急性脑梗死62例临床观察

目的探讨法舒地尔联合蚓激酶治疗急性脑梗死的临床疗效。方法选择本院2007年2月至2009年2月急性脑梗死患者122例,随机分为两组,治疗组和对照组。对照组采用常规治疗,治疗组在对照组治疗基础上给以法舒地尔和蚓激酶治疗,14d为一个疗程,共两个疗程。2个疗程结束后,对两组患者治疗前后进行神经功能缺损程度评分,并比较两组的临床疗效。结果治疗组的总有效率为91．9％,对照组的总有效率为70．O％,两组的总有效率比较,差异有统计学意义（P〈0．01）;治疗组治疗后神经功能缺损程度评分低于对照组,差异有统计学意义（P〈0．01）。结论法舒地尔联合蚓激酶治疗急性脑梗死临床效果显著,能够显著改善患者的神经功能,值得临床借鉴。     

不同浓度法舒地尔促进皮肤创面愈合作用的研究

目的：观察法舒地尔（HA1077）促进创面愈合的效果,并探讨HA1077与创面愈合的量效关系,寻找出促进创面愈合的最佳剂量。方法：18只Wistar大鼠背部左右两侧致直径为2cm的圆形皮肤缺损。随机3只动物6个创面为一组,分为6组,分别给予10、20、40、80和160μmol/L盐酸法舒地尔和生理盐水（对照组）创面喷洒,每个创面0.5ml,隔日创面追加喷洒。实验3、7、10d计算伤口面积,实验10d取创面组织,观察组织学变化。结果：各组大鼠创面面积随伤后时间延长而逐渐缩小,20μmol/L组创面面积明显小于同时间点其他各组,除实验7d与80μmol/L组创面面积比较差异无显著性外,其余各时间点差异均有显著性（P〈0.05）。病理学变化显示,创伤后10d,应用20μmol/L法舒地尔组创面新生肉芽组织生长及新生表皮生长速度明显优于其他各组。结论：HA1077可促进皮肤缺损创面愈合,以20μmol/LHA1077效果更为明显。     

法舒地尔对急性冠状动脉综合征患者血管内皮功能的影响

目的 研究法舒地尔对急性冠状动脉综合征(以下简称急性冠脉综合征)患者血管内皮功能的影响.方法 随机选择急性冠脉综合征患者80例,将入选患者按随机单盲法分为法舒地尔治疗组40例,常规治疗组40例,另外随机选择40例正常人做对照组.分别测定两组治疗前及治疗后4周血浆内皮素、一氧化氮含量.结果 急性冠脉综合征患者血浆一氧化氮水平明显下降,与对照组比较差异有统计学意义(P<0.01);血浆内皮素水平明显升高,与对照组比较差异有统计学意义(P<0.01);急性冠脉综合征组和常规治疗组两组治疗前血浆内皮素、一氧化氮水平比较差异无统计学意义(P>0.05).急性冠脉综合征组治疗后一氧化氮水平较前明显升高, 血浆内皮素水平较前明显降低,与治疗前比较差异有统计学意义(P<0.01),与常规治疗组治疗后比较差异亦有统计学意义(P<0.05).结论 法舒地尔对急性冠脉综合征患者具有保护血管内皮功能的作用. Abstract： Objective To explore the effect of fasudil on vascular endothelial function in patients with acute coronary syndrome.Methods Randomly selected patients with acute coronary syndrome in 80 cases, all patients were selected randomly divided into single-blind fasudil group of 40 patients, 40 patients with conventional treatment group, and randomly selected 40 cases of normal people to the control group. The two groups were measured before and after treatment for 2 weeks ET, nitric oxide.Results Acute coronary syndrome patients with decreased levels of nitric oxide, there was a significant difference compared with the control group (P<0.01).Plasma ET levels were significantly increased compared with the control group,and there was a significant difference (P<0.01).ET, nitric oxide levels were not significantly different between the two groups before treatment (P>0.05). The level of nitric oxide significantly increased, plasma ET levels significantly decreased than that before treatment and the difference was significant (P<0.01), and compared with the conventional treatment group, the difference was also significant (P<0.05).Conclusions Fasudil on patients with acute coronary syndrome has the protection of vascular endothelial function.     

Rho激酶抑制剂对急性缺血性脑卒中的治疗研究

目的评价Rho激酶抑制剂在急性缺血性脑卒中的临床疗效，方法选择急性缺血性脑卒中患者196例，治疗组98例、对照组98例，分别在入院时及治疗后2周对患者进行神经功能缺损评分并进行临床结局评定。结果治疗组患者神经功能缺损评分改善较对照组差异有统计学意义（P〈0．05，临床结局改善明显优于对照组。结论急性缺血性脑卒中患者急性期使用Rho激酶抑制剂能降低患者神经功能受损程度，抑制卒中后继发性脑损伤。     

Effects of the Rho-kinase inhibitors,Y-27632 and fasudil,on the corpus cavernosum from diabetic mice

Relaxant responses to two Rho-kinase inhibitors, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and fasudil, were compared in the corpus cavernosum obtained from diabetic and non-diabetic mice. Streptozotocin (100 mg kg(-1) day(-1), for 2 days) induced diabetes with a blood glucose level of 318+/-55.4 mg dl(-1); whereas it was 85.4+/-4.1 mg dl(-1) in control mice (P<0.05). Electrical field stimulation (40 V, 0.5 ms, 1, 2, 4, 8, 16 Hz for 15 s) and acetylcholine-induced relaxations were markedly attenuated in the corpus cavernosum from streptozotocin-diabetic mice whereas responses to Y-27632 (10(-9)-3 x 10(-5) M) and fasudil (10(-9)-3 x 10(-5) M) were not altered. EC(50) values for Y-27632 were 2.98+/-0.89 and 4.19+/-2.71 microM in the corpus cavernosum from control and diabetic mice, respectively (P>0.05). The values for fasudil were 7.42+/-4.91 and 3.53+/-1.41 microM in the corpus cavernosum from control and diabetic mice, respectively (P>0.05). These results may suggest that, in diabetes, the relaxant effects of the Rho-kinase inhibitors may not be changed and thus, they may have a beneficial therapeutic effect in diabetic erectile dysfunction.     

法舒地尔对慢性阻塞性肺疾病患者肺动脉高压及右心功能的疗效观察

目的：评价不同给药次数的法舒地尔对慢性阻塞性肺疾病(COPD)继发肺动脉高压治疗效果的差异。方法将72例COPD继发肺动脉高压患者随机分为常规治疗组、每日1次组、每日2次组，其中常规治疗组26例，每日1次组25例，每日2次组21例。常规治疗组行吸氧、抗感染、化痰、平喘、强心利尿或无创呼吸机辅助通气等治疗；每日1次组和每日2次组分别在常规治疗基础上加法舒地尔30 mg每天1次和每天2次滴注治疗。比较各组患者治疗前后测定肺动脉收缩压、动脉血二氧化碳分压(PaCO2)、N末基末端脑钠肽前体(NT-proBNP)水平及住院时间差异。结果用药后3组患者肺动脉收缩压、PaCO 2、NT-proBNP均有不同程度改善，法舒地尔治疗组改善幅度高于常规治疗组(P<0.05)。两两比较中肺动脉收缩压、PaCO 2在常规治疗组与每日1次组、常规治疗组与每日2次组之间存在统计学差异(P<0.05)；NT-proBNP仅在常规治疗组与每日2次组之间存在统计学差异(P<0.05)。3组患者住院时间比较，差异无统计学意义。结论法舒地尔能降低COPD继发的肺动脉高压，改善肺通气及右心功能。增加法舒地尔给药次数未发现能进一步降低COPD患者的肺动脉收缩压。     

法舒地尔对急性心肌梗死大鼠心肌的保护作用

目的:通过检测急性心肌梗死(AMI)大鼠左心室梗死面积及缺血区凋亡细胞来评价法舒地尔对大鼠AMI后心肌的保护作用.方法:雌性Wistar大鼠随机分为3组,AMI组:结扎左前降支(LAD);治疗组:术前1 h法舒地尔30 mg/kg腹腔注射,结扎LAD;假手术组:仅在LAD下穿线但不结扎.术后24 h,伊文蓝-红四氮唑双染色,确定缺血面积和梗死面积,TUNEL法检测缺血区凋亡细胞,免疫组织化学染色法检测缺血区bcl-2和bax的表达,逆转录一聚合酶链式反应测定Rho激酶mRNA的表达.结果:治疗组与AMI组比较,梗死面积显著减小(26.04±2.51)%:(32.27±3.07)%,P＜0.01,缺血面积差异无统计学意义.AMI组与假手术组比较,凋亡指数明显增加(31.94±3.03):(2.44±1.37),P＜0.01,bcl-2表达降低,bax表达增加,Rho激酶mRNA表达增加(均P＜0.01).而治疗组与AMI组比较,凋亡指数显著降低.bcl-2表达增加,bax表达降低,Rho激酶mRNA表达降低,均P＜0.01.结论:Rho激酶参与了AMI心肌细胞的凋亡,法舒地尔的心肌保护作用与其抗心肌细胞凋亡效应有关.     

Effect of Fasudil on Remyelination Following the Cuprizone-Induced Demyelination in Male C57BL/6 Mice

Background Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disease of the central nervous system (CNS) characterized by de-/ remyelination, neuroinflammation and oligodendrocyte loss. Although a greater understanding of MS have increased acquaintance of the pathogenesis and pathophysiology, the exploration of treatment is still challenging. Fasudil, one of the most thoroughly studied Rho kinase (ROCK) inhibitors, has been shown to have effects in neurodegenerative diseases. However, the effect of Fasudil on preventing the progression of the demyelination in MS has not been evaluated. Cuprizone (CPZ)-induced demyelination is a model used to study de-/ remyelination in the CNS. Some aspects of the histological pattern induced by CPZ are similar to MS. The aim of the study is to investigate the effect of Fasudil on CPZ-induced demyelination, and to explore the mechanisms for the possible remyelination. Materials and Methods Male C57BL/6 mice (10–12 weeks old) were assigned into normal group, fed a normal diet; CPZ group, fed CPZ and intraperitoneally (i.p.) injected with normal saline after 4 weeks for consecutive 2 weeks; Fasudil-treated CPZ group, which were i.p. injected with Fasudil (40 mg/kg/day) after 4 weeks for consecutive 2 weeks. All groups were assessed by Elevated plus-maze (EPM) test and Pole test at the end of the experiment. For examing the extent of demyelination, Luxol Fast Blue (LFB) staining, Black Gold II and myelin basic protein (MBP) immunohistochemistry staining were used for slides of brains. Splenic MNCs were fixed and stained with the following antibodies: Alexa Fluor B220, FITC-CD4/PE-IFN-γ, FITC-CD4/PE-IL-17. At least 10, 000 events were collected using flow cytometer. Results Following CPZ-exposure, mice presented a lower density of LFB, Black Gold II and MBP expression, loss of mature oligodendrocytes. Spleen atrophy was observed in CPZ-group compared to normal mice, and we firstly found that CPZ feeding induced the formation of MOG antibody. Fasudil treatment improved behavioral abnormality, promoted remyelination, inhibited spleen atrophy and production of MOG antibodies, prevented the infiltration of peripheral T cells, B cells, macrophages, and declined the neuroinflammation by inhibiting Iba1+iNOS+, Iba1+NF-κB+ microglia. Fasudil treatment also reduced the levels of IL-1β, IL-6 and TNF-α. Discussion In this study, we demonstrated that demyelinating model was successfully established. Then we tested whether Fasudil plays a remyelinating role in this model. Spleen atrophy was observed after CPZ-feeding compared to normal mice. Previous studies have shown that splenic atrophy in experimental stroke may contribute to brain injury possibly through the release of inflammatory mediators and spleen-derived inflammatory cells to the circulation and migration into the brain, which aggravate the brain inflammatory response and led to secondary injure. At present, we lack direct evidence to elucidate the mechanisms for spleen atrophy in CPZ-induced demyelination. We firstly found that CPZ-feeding induced the formation of MOG antibody. Recent study indicated that BBB hyperpermeability precedes demyelination in CPZ-demyelinating model. Another study suggested that debris of damaged cells in the CNS may present as antigens after penetrating the BBB, giving rise to autoantibodies. Therefore, it is possible that the myelin debris produced the destruction of myelin sheath can enter the blood circulation and stimulate the immune response of T and B cells. We found that MOG antibody was elevated in the supernatant of cultured plenocytes, indicating that the MOG antibodies were derived from peripheral immune cells. Our results showed that the level of MOG antibody in the brain homogenate of CPZ-treated mice was higher than that of normal mice, suggesting that antibodies can enter brain tissue and anti a-synuclein antibody was negative, which indicate that anti MOG antibody is a specific antibody. In our study, MOG antibody was capable of being detected in the brain of CPZ-treated mice, providing a possibility for specific MOG antibody-mediated oligodendrocyte damage. CPZ induced a wide range of Iba-1+ microglia, which was inhibited by Fasudil. These results suggest that the suppression of inflammatory microenvironment may contribute to the remyelination. In conclusion, the administration of Fasudil promoted remyelination by multiple mechanisms.     

法舒地尔治疗AECOPD相关性肺动脉高压患者的临床近期疗效分析

目的探讨法舒地尔治疗慢性阻塞性肺疾病急性加重期（AECOPD）相关性肺动脉高压的临床近期疗效。方法选取本院2010年10月-2013年10月诊治的AECOPD相关性肺动脉高压患者110例,采用随机数字表法分为两组,55例患者实施常规治疗为对照组,55例患者在常规治疗基础上加用法舒地尔治疗为观察组,比较两组患者肺功能指标的改变情况、相关指标的改变情况、治疗效果。结果治疗后,两组患者FEV1（1s用力呼气容积）、FVC（用力肺活量）、FEV1/FVC（气道阻塞的肺量测定）、血氧饱和度、动脉血氧分压、6min步行距离均显著增加,而肺动脉收缩压均显著降低。观察组患者FEV1、FVC、FEV1/FVC、血氧饱和度、动脉血氧分压、6min步行距离、总有效率均明显高于对照组,观察组患者肺动脉收缩压明显低于对照组,差异均有统计学意义（P〈0.05）。结论法舒地尔是治疗AECOPD相关性肺动脉高压的有效药物,可明显改善患者的心肺功能,临床近期疗效显著,值得临床推广使用。