法舒地尔对阻塞性黄疸大鼠肝缺血再灌注损伤的影响

目的 探讨法舒地尔对阻塞性黄疸大鼠肝缺血再灌注损伤的影响.方法 成熟SD大鼠160只随机分成实验组(A组)及对照组(B组)两大组,两组再分别分为4个亚组,分别为假手术组(A1、B1组)、阻塞性黄疸组(A2、B2组)、肝缺血再灌注组(A3、B3组)及阻塞性黄疸+肝缺血再灌注组(A4、B4组).A2、B2组采用双重结扎切断胆总管的方法建立模型,A3、B3组采用阻断肝门部血管30 min后再灌注的方法建立模型.A4、B4组于建立阻塞性黄疸模型1周后再次建立缺血再灌注模型.A组于缺血前30 min腹腔内注射法舒地尔10 mg/kg,B组对应注射等量生理盐水.两组分别于再灌注0h、1h、2h、6h取材,检测血清肝功能改变及血清内皮素1水平.采用SPSS软件对重复测量结果进行统计分析,光镜下观察肝脏病理学改变.结果 实验组各时点血清转氨酶水平、血清内皮素1水平均显著低于对照组(P＜0.05),实验组各时点光镜下肝脏病理组织学损伤也较对照组明显减轻.结论 法舒地尔对阻塞性黄疸大鼠的肝缺血再灌注损伤具有保护作用.     

法舒地尔对脓毒症所致急性肺损伤及肺组织中HMGB1表达的影响

目的观察法舒地尔对小鼠脓毒症所致急性肺损伤的影响及其使用与否对肺组织中HMGB1表达量的影响。方法将48只BALB-C小鼠随机分为对照组、盲肠结扎穿刺（CLP）组、法舒地尔预处理组,在6、24 h时间点取血、肺泡灌洗液及鼠肺用于结果分析。结果在6、24 h时间点,法舒地尔可以显著降低CLP所致的小鼠血清中TNF-α及HMGB1和肺泡灌洗液中蛋白浓度的增加。除此之外,法舒地尔预处理还可以逆转CLP诱导的小鼠肺组织病理形态改变。同时,法舒地尔能减少CLP所致小鼠肺组织中HMGB1 mRNA表达量的增加。结论法舒地尔能减轻CLP小鼠所致的肺损伤并降低肺组织中HMGB1的表达。     

Fasudil mediates cell therapy of EAE by immunomodulating encephalomyelitic T cells and macrophages

Although Fasudil has shown therapeutic potential in EAE mice, the mechanism of action are still not fully understood. Here, we examined the immunomodulatory effect of Fasudil on encephalitogenic mononuclear cells (MNCs), and tested the therapeutic potential of Fasudil‐treated MNCs in active EAE. Fasudil inhibited expression of CCL20 on T cells and migration of T cells, decreased CD4⁺IFN‐γ⁺ and CD4⁺IL‐17⁺ T cells, but increased CD4⁺IL‐10⁺ and CD4⁺TGF‐β⁺ T cells. Fasudil reduced expression of CD16/32 and IL‐12, while elevating expression of CD206, CD23, and IL‐10. Fasudil also decreased levels of iNOS/NO, enhanced levels of Arg‐1, and inhibited the TLR‐4/NF‐κB signaling and TNF‐α, shifting M1 macrophage to M2 phenotype. These modulatory effects of Fasudil on T cells and macrophages were not altered by adding autoantigen MOG_35–55 to the culture, i.e., autoantigen‐independent. Further, we observed that, in vitro, Fasudil inhibited the capacity of encephalitogenic MNCs to adoptively transfer EAE and reduced TLR‐4/p‐NF‐κB/p65 and inflammatory cytokines in spinal cords. Importantly, Fasudil‐treated encephalitogenic MNCs exhibited therapeutic potential when injected into actively induced EAE mice. Together, our results not only provide evidence that Fasudil mediates the polarization of macrophages and the regulation of T cells, but also reveal a novel strategy for cell therapy in MS.     

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.     

法舒地尔不同给药途径治疗介入操作中脑血管痉挛的疗效评价

目的探讨介入操作中发生脑血管痉挛(CVS)时,法舒地尔不同给药途径治疗CVS的临床疗效,并观察其安全性及预后,为临床治疗提供依据。方法回顾性选取2009年5月至2014年5月介入操作发生CVS的患者80例资料。随机分为对照组和观察组,两组各40例。对照组:法舒地尔30 mg加入0.9%氯化钠注射液100 ml通过静脉点滴途径给药;观察组:法舒地尔15 mg加入0.9%氯化钠注射液100 ml,经微导管注入脑血管痉挛发生部位。观察两组患者的临床疗效,发挥作用时间及安全性。结果观察组患者总有效率为95.00%(38/40),高于对照组80.00%(32/40),差异具有统计学意义(P0.05)。观察组患者平均解痉时间为11.71±3.45 min,少于对照组24.68±4.42 min,差异具有统计学意义(P0.05)。观察组患者治疗后GCS评分和GOS评分分别为13.16±0.52和4.82±0.34,均高于对照组治疗后,差异具有统计学意义(P0.05)。两组患者不良反应结果比较,差异无统计学意义(P0.05)。结论脑血管疾病介入操作治疗中发生CVS,通过微导管动脉注入法舒地尔,应用剂量小,临床治疗效果更佳,起效时间短,预后良好,安全有效。     

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。     

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.     

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。