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盐酸法舒地尔治疗急性脑梗死临床观察

作者 / Author:余 旭

摘要 / Abstract:

目的 分析盐酸法舒地尔治疗急性脑梗死的疗效及对血管内皮生长因子的影响。方法 选取信阳市中心医院2013-02—2016-08收治的120例急性脑梗死患者,随机分为实验组与对照组,每组60例。对照组应用尼莫地平+阿司匹林治疗,实验组应用盐酸法舒地尔+阿司匹林治疗。分析2组总有效率、治疗前后神经功能缺损评分、血清CRP、肿瘤坏死因子、白细胞介素6(IL-6)、白细胞介素4(IL-4)以及对血管内皮生长因子(VEGF)的影响等参数指标。结果 (1)实验组总有效率95.00%(57/60),对照组为87.67%(46/60),实验组总有效率高于对照组(P<0.05);(2)治疗前2组神经功能缺损评分比较差异无统计学意义(P>0.05);治疗后,实验组神经功能缺损评分显著低于对照组(P<0.05);(3)治疗前2组血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平比较差异无统计学意义(P>0.05);治疗后,实验组血清CRP、肿瘤坏死因子、IL-6、IL-4以及血管内皮生长因子(VEGF)表达水平显著低于对照组,差异有统计学意义(P<0.05)。结论 盐酸法舒地尔有效减少急性脑梗死患者血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平,提高临床疗效。

关键词 / KeyWords:

脑梗死,盐酸法舒地尔,C反应蛋白,白细胞介素6,白细胞介素4,血管内皮生长因子
盐酸法舒地尔治疗急性脑梗死临床观察
余 旭
信阳市中心医院重症医学科,河南信阳 464000
作者简介:余旭,Email:371391245@qq.com
 
摘要 目的 分析盐酸法舒地尔治疗急性脑梗死的疗效及对血管内皮生长因子的影响。方法 选取信阳市中心医院2013-02—2016-08收治的120例急性脑梗死患者,随机分为实验组与对照组,每组60例。对照组应用尼莫地平+阿司匹林治疗,实验组应用盐酸法舒地尔+阿司匹林治疗。分析2组总有效率、治疗前后神经功能缺损评分、血清CRP、肿瘤坏死因子、白细胞介素6(IL-6)、白细胞介素4(IL-4)以及对血管内皮生长因子(VEGF)的影响等参数指标。结果 (1)实验组总有效率95.00%(57/60),对照组为87.67%(46/60),实验组总有效率高于对照组(P<0.05);(2)治疗前2组神经功能缺损评分比较差异无统计学意义(P>0.05);治疗后,实验组神经功能缺损评分显著低于对照组(P<0.05);(3)治疗前2组血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平比较差异无统计学意义(P>0.05);治疗后,实验组血清CRP、肿瘤坏死因子、IL-6、IL-4以及血管内皮生长因子(VEGF)表达水平显著低于对照组,差异有统计学意义(P<0.05)。结论 盐酸法舒地尔有效减少急性脑梗死患者血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平,提高临床疗效。
关键词】 脑梗死;盐酸法舒地尔;C反应蛋白;白细胞介素6;白细胞介素4;血管内皮生长因子
中图分类号】  R743.33    【文献标识码】  A    【文章编号】  1673-5110(2019)04-0380-06  DOI:10.12083/SYSJ.2019.04.123
 
Application of fasudil hydrochloride in patients with acute cerebral infarction and its effect on vascular endothelial growth factor
YU Xu
Department of Critical Care MedicineXinyang Central HospitalXinyang 464000,China
Abstract】  Objective  To analyze the application of fasudil hydrochloride in patients with acute cerebral infarction and its effect on vascular endothelial growth factor.Methods  From February 2013 to August 2016,120 patients with acute cerebral infarction admitted to Xinyang Central Hospital were selected as the study subjects.They were randomly divided into experimental group and control group according to the order of admission,with 60 cases in each group.The control group was treated with nimodipine + aspirin,and the experimental group was treated with fasudil hydrochloride + aspirin.Statistical analysis was performed using SPSS 20.0 statistical software.The total effective rate of clinical treatment,neurological deficit score before and after treatment,serum high-sensitivity C-reactive protein,tumor necrosis factor,interleukin-6,interleukin-4 and Parameters such as the influence of vascular endothelial growth factor (VEGF).Results  The total effective rate of clinical treatment in the experimental group was 95.00% (57/60),and the total effective rate in the control group was 87.67% (46/60).The total effective rate of clinical treatment in the experimental group was much higher than that in the control group (P<0.05).Before treatment,there was no significant difference in neurological deficit score between the experimental group and the control group (P>0.05).After treatment,the neurological deficit score of the experimental group was significantly lower than that of the control group.Group (P<0.05).There was no significant difference in serum high-sensitivity C-reactive protein,tumor necrosis factor,interleukin-6,interleukin-4 and vascular endothelial growth factor (VEGF) levels between the two groups before treatment.Significance (P>0.05);after treatment,the serum levels of high-sensitivity C-reactive protein,tumor necrosis factor,interleukin-6,interleukin-4 and vascular endothelial growth factor (VEGF) in the experimental group were significantly lower than those in the control group.Statistical significance (P<0.05).Conclusion  Fasudil hydrochloride can effectively reduce the levels of serum CRP,tumor necrosis factor,IL-6,IL-4 and VEGF in patients with acute cerebral infarction,and improve the total effective rate of treatment.
Key words】  Cerebral infarction;Fasudil hydrochloride;C-reactive protein;Interleukin-6;Interleukin-4;Vascular endothelial growth factor
 
        急性脑梗死具有发病率高和致残率高等特点,有溶栓、抗血小板聚集和抗凝等治疗手段[1-5]。现阶段来看,溶栓是最主要的治疗方法,由于其具有严格的适应证和禁忌证,所以可导致严重并发症。因此,保护好急性脑梗死患者的受损神经元成为研究热点[6-10]。急性脑梗死患者致残率较高的主要原因是缺血后的级联炎症。血管内皮生长因子是内皮细胞有丝分裂原,VEGF是目前发现最为主要作用于血管内皮的生长因子,能够很大程度上增加微血管的通透性,促进血管的生成[11-15]。盐酸法舒地尔作为一种钙离子拮抗剂,具有保护神经元的作用。本文分析盐酸法舒地尔治疗急性脑梗死的疗效及对血管内皮生长因子的影响。
 
1  资料与方法
1.1  临床资料 选取信阳市中心医院2013-02—2016-08收治的120例急性脑梗死患者,均符合急性脑梗死疾病的诊断标准,所有患者经CT检查确诊,均知晓本次实验并签署相关同意书;排除严重心、肺、肾功能不全者,大面积急性脑梗死出现出血者,近期心绞痛者,短暂性脑缺血发作者,免疫系统疾病者以及精神障碍者。对照组男40例,女20例;年龄(62.21±6.36)岁;病程(2.51±1.15)d;体质量(62.02±11.11)kg;神经功能缺损评分:10例重型,35例中型,15例轻型。实验组男38例,女22例;年龄(61.99±6.28)岁;病程(2.52±1.11)d;体质量(62.05±10.79)kg;神经功能缺损评分:9例重型,37例中型,14例轻型。2组一般资料比较差异无统计学意义(P>0.05),具有可比性。
1.2  方法 2组患者均采取20%甘露醇溶液(华润双鹤药业股份有限公司,国药准字H11020861)2.0 mL静滴,80~120 mg盐酸川芎嗪(哈尔滨三联药业股份有限公司,国药准字H20041171)+0.9%氯化钠注射液250~500 mL静滴,1~2次/d。对照组采取30~120 mg尼莫地平(天津市中央药业有限公司,国药准字H109140)口服,3次/d,共2周;阿司匹林(广东九明制药有限公司,国药准字H44021139)50~150 mg/次,1次/d,连服2周。
        实验组采取30 mg盐酸法舒地尔(天津红日药业股份有限公司,国药准字H20040356)50~100 mL生理盐水静滴30 min,2~3次/d;阿司匹林(广东九明制药有限公司,国药准字H44021139)用法同对照组。
1.3  观察指标 分析2组总有效率、治疗前后神经功能缺损评分、血清CRP、肿瘤坏死因子、IL-6、IL-4以及对血管内皮生长因子(VEGF)指标。神经功能缺损评分:(1)0~15分为轻型;(2)16~30分为中型;(3)31~45分为重型。
1.4  疗效评价标准 治愈:治疗后病残程度0级且神经功能缺损评分减少≥90%;显效:治疗后病残程度1~3级且神经功能缺损评分减少50%~89%;有效:治疗后神经功能缺损评分减少20%~49%;无效:治疗后神经功能缺损评分增加19%以上。
1.5  统计学方法 采用SPSS 20.0统计学软件进行统计学分析,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料以百分率(%)表示,采用χ2检验,P<0.05为差异有统计学意义。
 
2  结果
2.1  2组总有效率比较 实验组总有效率高于对照组(P<0.05)。见表1。
2.2  2组治疗前后神经功能缺损评分比较 治疗前2组神经功能缺损评分比较差异无统计学意义(P>0.05),治疗后实验组神经功能缺损评分显著低于对照组(P<0.05)。见表2。
2.3  2组治疗前后炎症因子以及血管内皮生长因子水平比较 治疗前2组血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平比较差异无统计学意义(P>0.05);治疗后实验组血清CRP、肿瘤坏死因子、IL-6、IL-4及血管内皮生长因子(VEGF)表达水平显著低于对照组,差异有统计学意义(P<0.05)。见表3。
表1  2组总有效率比较  [n(%)]
Table 1  Comparison of total effective rate of clinical treatment in 2 groups  [n(%)] 
组别 n 治愈 显效 有效 无效 总有效率
实验组 60 46(76.67) 7(11.67) 4(6.67) 3(5.00 ) 57(95.00)
对照组 60 30(50.00) 3(5.00) 13(21.67) 14(23.33) 46(87.67)
t   10.352 63 15.362 58 17.47151 19.365 22 14.445 65
P   0.05 0.05 0.05 0.05 0.05
表2  2组治疗前后神经功能缺损评分比较  (x±s,分)
Table 2  Comparison of neurological deficit scores before and after treatment in 2 groups  (x±s,score) 
组别 n 治疗前神经功能缺损评分 治疗后神经功能缺损评分
实验组 60 36.02±2.26 9.47±3.23
对照组 60 35.96±4.48 22.55±7.63
t   11.265 52 16.869 56
P   0.05 0.05
表3  2组治疗前后炎症因子以及血管内皮生长因子水平比较  (x±s)
Table 3  Comparison of inflammatory factors and vascular endothelial growth factor levels
before and after treatment in 2 groups  (x±s)
 
组别 n CRP(mg/L)   肿瘤坏死因子(μg/L)   IL-6(ng/L)   IL-4(ng/L)   VEGF(ng/L)
治疗前 治疗后   治疗前 治疗后   治疗前 治疗后   治疗前 治疗后   治疗前 治疗后
实验组 60 27.36±9.74 9.55±3.46   42.87±5.23 43.68±4.36   11.77±3.36 15.24±3.36   6.17±1.09 4.30±0.72   354.77±49.33 176.54±31.05
对照组 60 26.98±8.88 15.46±6.11   42.85±5.45 55.12±5.29   11.80±2.69 29.66±2.37   6.18±0.89 5.56±0.85   347.25±43.18 250.02±29.78
t   2.122 5.236   1.012 3.362   1.774 8.892   1.002 0.158   1.111 6.362
P   >0.05 <0.05   >0.05 <0.05   >0.05 <0.05   >0.05 <0.05   >0.05 <0.05
3  讨论
        炎症因子的释放是脑缺血后炎症反应的关键环节,中性粒细胞是缺血区白细胞浸润的最早效应细胞,灌注损伤5 h 后开始升高,在25~47 h内达到最高峰,继而导致血管基底膜被破坏和细胞毒性酶被释放,使得脑缺血炎症反应进入到恶性循环状态中,加重缺血性脑损伤。IL-6、IL-4和肿瘤坏死因子α(TNF-α)均是脑缺血后主要炎症因子,IL-6诱导血管内皮细胞黏附因子的表达,从而促进IL-4和IL-8等细胞因子的合成,引起血管炎性反应[16-20]。TNF-α是诱导细胞凋亡且促进血管内皮进入血栓状态,使得梗死体积被扩大。由于经济条件,部分急性脑梗死患者溶栓治疗的方法有限,只能常规药物治疗[21-23]
        动物实验表明,神经细胞凋亡和坏死是导致急性脑梗死患者神经功能损害的重要原因。炎症反应在缺血性脑损伤的病理过程中起重要作用,过度炎症反应会加重细胞缺血缺氧情况[24-30]。本研究显示,治疗前2组血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF水平比较差异无统计学意义(P>0.05);治疗后实验组血清CRP、肿瘤坏死因子、IL-6、IL-4以及VEGF表达水平显著低于对照组(P<0.05)。血清CRP是反映体内炎症活动的精确客观指标之一,能够反映组织细胞有无坏死,与炎症和细胞组织损伤成正比。血清CRP通常可作为评价心血管疾病危险性的炎症指标,也可作为急性脑梗死患者病情严重程度的客观指标。VEGF具有以下特性:(1)促进内皮细胞增殖;(2)诱导血管形成。在急性脑梗死患者的病理生理过程中,中心缺血区神经细胞在一定时间内发生不可逆损伤,VEGF能够促进脑缺血区的血管增生,从而改善区域内微循环的血流供应,减少急性脑梗死的总面积。研究显示,测定VEGF水平对急性脑梗死面积大小的预测和病情严重程度的预测等具有很大价值[31-35]
        钙离子拮抗剂在急性脑梗死患者治疗过程中能够改善微循环及减轻脑水肿,其在缺血性脑损伤的保护中受到广泛关注[36-39]。尼莫地平和阿司匹林等能够透过血脑屏障进入脑组织,从而起到保护脑组织的作用[40-42]。盐酸法舒地尔能够与RHo激酶ATP位点结合,增强肌球蛋白磷酸酶的活性作用,使得平滑细胞从收缩状态进入舒张状态,一氧化氮的合成增多,抑制自由基的形成,保护患者的神经元[43-46]。RHo信号通路的主要生理功能是调节细胞骨架蛋白的合成和移动等,参与细胞的整体生命过程[47-52]。盐酸法舒地尔能够有效改善粥样硬化斑块,降低血管内皮细胞的表达水平,最终改善脑组织微循环状况[53-54]。因此,盐酸法舒地尔能够有效降低急性脑梗死患者血清CRP、肿瘤坏死因子、IL-6、IL-4及VEGF水平,提高有效率。
 
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(收稿2018-04-12)
本文责编:关慧
本文引用信息:余旭.盐酸法舒地尔治疗急性脑梗死临床观察[J].中国实用神经疾病杂志,2019,22(4):380-385.DOI:10.12083/SYSJ.2019.04.123

Reference information:YU Xu.Application of fasudil hydrochloride in patients with acute cerebral infarction and its effect on vascular endothelial growth factor[J].Chinese Journal of Practical Nervous Diseases,2019,22(4):380-385.DOI:10.12083/SYSJ.2019.04.123 

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