Fasudil hydrochloride could promote axonal growth through inhibiting the activity of ROCK

Objective: This study aims to investigate the neuroprotective effect of Rho kinase inhibitor fasudil hydrochloride in ischemia/reperfusion injury N2a neuron. Methods: In vitro, N2a cells induced by ischemia and ischemia-reperfusion were treated with fasudil hydrochloride, cell damage was analyzed by MTT. On the other hand, the cytoskeleton of N2a cells was scanned through immunofluorescence techniques by Confocal Laser Microscopy which stained with FITC-phalloidin for F-actin visualization. Results: The activation of ROCK-II increased significantly in the damaged local during the following phase of ischemia/reperfusion injury. Ischemia induced a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity of the peripheral filament actin bands and formation of the long and thick stress fibers, but pretreatment of Fasudil hydrochloride could reversed the changes of ultra-structure on the cellular surface. MTT assay showed that Fasudil hydrochloride could prolong the survival time of the N2a cells after mimic ischemia-reperfusion for 24 h. Conclusions: The activation of ROCK-II has an exceptional hoist after ischemia/reperfusion injury, it is likely to induce the collapse of the growth cone through MLC-P. Fasudil hydrochloride could promote axonal growth on inhibitory of ROCK activity.     

Rho激酶抑制剂治疗短暂性脑缺血发作疗效观察

目的：分析Rho激酶抑制剂治疗短暂性脑缺血发作的效果。方法将172例短暂性脑缺血发作患者分为两组，对照组给予常规治疗，治疗组给予法舒地尔注射液治疗。结果治疗组治疗总有效率高于对照组，不良反应轻微不影响治疗。结论 Rho激酶抑制剂治疗短暂性脑缺血发作效果显著。     

奥扎格雷联合法舒地尔对短暂性脑缺血发作患者脑氧代谢及炎性指标的影响研究

目的:探讨奥扎格雷联合法舒地尔对短暂性脑缺血发作患者脑氧代谢及炎性指标的影响。方法:选择采用阿司匹林进行治疗的31例短暂性脑缺血发作患者为对照组,同期采用奥扎格雷联合法舒地尔进行治疗的31例患者为观察组,将两组患者治疗前及治疗后5 d、10 d的脑氧代谢及炎性指标进行检测及比较。结果:观察组治疗后5 d、10 d的SjvO2及CjvO2均高于对照组,而Da-jvO2及CaO2均低于对照组,血清炎性指标均低于对照组,差异有统计学意义(P<0.05)。结论:奥扎格雷联合法舒地尔可显著改善短暂性脑缺血发作患者的脑氧代谢及炎性指标,可有效改善患者的疾病状态。     

Impacts of Rho kinase inhibitor Fasudil on Rho/ROCK signaling pathway in rabbits with optic nerve injury

Objective: The aim of this study was to study the impacts of Rho kinase inhibitor Fasudil on expressions of Rho/ROCK signaling pathway associated genes in rabbits with optic nerve injury (ONI), and to explore the therapeutic mechanisms towards ONI. Methods: The rabbit ONI model was established, then the rabbits were divided into model group (treated with saline), control group (treated with dexamethasone, Dex), and intervention group (treated with Fasudil, Fas). The eyeball and optic nerve were sampled at 3, 7, 14 and 21 days after injury. The morphological changes of retina and optic nerve were observed. The expressions of RhoA, Caspase-3, Rock 2 and Nogo-A gene were determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Results: At different time after injury, there were significant differences of RhoA, Caspase-3, Rock 2 and Nogo-A gene expression among three groups (P < 0.05). Conclusions: After ONI, Fas can decrease the expression of Caspase-3 gene, and down-regulate the expressions of Nogo-A and Rock 2 gene. Therefore, it can treat ONI through affecting the Rho/ROCK signaling pathway.     

沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床观察

目的 观察沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床效果。方法 选取于延安市人民医院心内科住院的冠心病心力衰竭患者80例,随机分成对照组和观察组各40例,均接受常规治疗,对照组采用沙库巴曲缬沙坦治疗,观察组采用沙库巴曲缬沙坦联用法舒地尔,比较两组患者的临床疗效、治疗前后左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、血浆脑钠肽(NT-proBNP)、血清可溶性细胞间黏附分子-1(sICAM-1)和血浆内皮微粒(EMPs)水平及不良反应。结果 观察组总有效率高于对照组,差异有统计学意义(P＜0.05)。治疗前,两组患者LVEDD、LVESD、LVEF、NT-proBNP、EMPs、sICAM-1对比,差异无统计学意义(P＞0.05);治疗后,两组患者LVEDD、LVESD、LVEF、NT-proBNP、EMPs、sICAM-1均较本组治疗前明显改善,且观察组改善更显著,差异有统计学意义(P＜0.05)。两组患者不良反应发生率低。结论 沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床效果显著,可抑制心肌重塑,降低炎症因子水平,改善心功能,安全性高。     

法舒地尔通过Rho-ROCK通路抑制高糖诱导的单核细胞与内皮细胞黏附

目的观察Rho激酶抑制剂法舒地尔能否抑制高糖诱导的单核细胞(THP-1)与人脐静脉内皮细胞黏附,初步探讨其潜在机制。方法使用荧光显微镜观察荧光标记的THP-1与人脐静脉内皮细胞黏附。血管细胞黏附分子1和单核细胞趋化蛋白1的mRNA及蛋白表达水平分别通过RT-PCR、Western blot检测。使用Western blot检测RhoA、ROCK-1、p-MYPT及MYPT蛋白表达水平变化。结果法舒地尔显著抑制高糖诱导的THP-1与人脐静脉内皮细胞黏附,并呈剂量依赖性,其中,低浓度法舒地尔(10-6 mmol/L)干预24 h黏附减少约33.4%,高浓度法舒地尔(10-5 mmol/L)干预24 h黏附减少约42.8%(P值均0.05),干预12 h组趋势相同。法舒地尔显著减低高糖诱导的人脐静脉内皮细胞血管细胞黏附分子1及单核细胞趋化蛋白1的mRNA及蛋白表达水平,并呈时间依赖性和剂量依赖性。高糖显著增加p-MYPT/MYPT比值,而法舒地尔减弱高糖对p-MYPT/MYPT比值的影响,抑制Rho/RCOK通路激活。结论法舒地尔抑制高糖诱导的THP-1与人脐静脉内皮细胞黏附,减低高糖诱导的人脐静脉内皮细胞血管细胞黏附分子1和单核细胞趋化蛋白1的表达,减少高糖诱导的Rho/RCOK通路激活,提示法舒地尔可能成为新的糖尿病大血管病变治疗药物。     

法舒地尔在难治性高血压治疗中的应用

目的 评价法舒地尔在难治性高血压治疗中的地位.方法 选择我院2009年1月至2013年9月所有符合难治性高血压诊断标准的患者68例,随机分为试验组34例和对照组34例.对照组采用规范的个体化口服降压治疗措施.试验组除采用规范的药物抗高血压治疗外,均予以应用法舒地尔静点.比较两组患者治疗2周后血压下降程度、达标率、联用药物种类及不良反应之间的差异.结果 试验组与对照组相比,在24 h平均收缩压（141.91±16.36 vs 149.23±13.38） mmHg、舒张压（78.71±13.60 vs 86.94±11.72）mmHg、平均动脉血压（99.77±11.77 vs 107.71±9.31）mmHg方面均下降明显,达标率明显高于对照组（70.6％ vs 44.1％）,且用药种类明显减少（4.06±0.78 vs 4.44±0.56）,而不良反应未见明显升高（32.4％ vs 55.9％）.结论 法舒地尔能显著降低血压水平,提高住院期间高血压控制达标率,减少联用药物的种类,是治疗难治性高血压的重要辅助治疗措施之一.     

盐酸法舒地尔注射液治疗急性脑梗死疗效观察

目的探讨盐酸法舒地尔注射液治疗急性脑梗死的临床疗效。方法 114例急性脑梗死患者随机分为观察组和对照组,观察组54例采用盐酸法舒地尔注射液治疗,对照组60例采用一般方法治疗。治疗前后对患者的临床神经功能缺损程度及生活质量进行评分,比较两组生活质量评分及总有效率。结果观察组和对照组治疗后神经功能缺损程度与治疗前比较差异均有统计学意义（P〈0.05）。观察组和对照组在治疗后相比差异有统计学意义（P〈0.05）。两组总有效率差异有统计学意义（P〈0.05）。结论盐酸法舒地尔注射液能够有效改善患者的神经功能缺损,促进急性脑梗死患者康复,是治疗急性脑梗死的有效方法。     

法舒地尔辅助高压氧治疗椎-基底动脉供血不足性眩晕的临床效果

目的：研究法舒地尔辅助高压氧治疗椎-基底动脉供血不足性眩晕的临床效果。方法选取2012年1月~2014年1月本科收治的66例椎-基底动脉供血不足性眩晕患者,将其随机分为观察组34例和对照组32例。观察组采用法舒地尔药物治疗,同时给予高压氧治疗;对照组单纯给予常规传统药物治疗。治疗10 d后观察两组的临床疗效,对比椎、基底动脉血流改善情况。结果治疗10 d后,观察组总有效率高于对照组（P〈0.05）;观察组经颅多普勒（TCD）检测椎、基底动脉平均血流速度快于对照组（P〈0.05）;观察组和对照组治疗后未发现明显不良反应。结论法舒地尔辅助高压氧治疗椎-基底动脉供血不足性眩晕,临床效果较好,无明显不良反应,值得推广。     

Administration of the Rho-Kinase Inhibitor Fasudil Before Ischemia or just After Reperfusion,but not 30 min After Reperfusion,Protects the Stunned Myocardium in Swine

OBJECTIVES: We assessed the effect of administration time for fasudil treatment of the stunned myocardium in 40 anesthetized open chest swine. MATERIALS AND METHODS: All swine were subjected to 12 min ischemia followed by reperfusion to generate stunned myocardium. Group A (n = 11) received saline in place of fasudil both before ischemia and after reperfusion. Group B (n = 10) received 30 min intravenous fasudil at a rate of 13 mug/kg/min starting 45 min before ischemia and received saline after reperfusion. Groups C (n = 10) and D (n = 9) received saline before ischemia, and received fasudil at a rate of 13 mug kg(-1) min(-1) starting just before reperfusion in group C and 30 min after reperfusion in group D. In both groups, treatment lasted 30 min. Myocardial contractility was assessed by percent segment shortening (%SS). RESULTS AND DISCUSSION: Three swine in group A, 2 swine in each of groups B and C, and one swine in group D had ventricular fibrillation or tachycardia after reperfusion and were excluded from further analysis. The changes of %SS from baseline at 90 min after reperfusion in groups B and C were 68 +/- 8% and 75 +/- 8%, respectively, which were significantly higher than in group A or D (47 +/- 10% or 43 +/- 8%). CONCLUSION: We conclude that fasudil administered before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium.