丁苯酞胶囊对脑动脉粥样硬化性狭窄所致脑低灌注的改善

DL-3-n-butylphthalide improves cerebral hypoperfusion caused by cerebral artherosclerotic stenosis

目的:探讨丁苯酞胶囊改善脑动脉粥样硬化性狭窄所致脑低灌注的作用。方法:采用单中心、随机、双盲、安慰剂对照临床研究,将120例颈动脉系统严重狭窄且伴有脑低灌注患者按1∶1比例分配至治疗组和对照组。治疗组服用丁苯酞胶囊0.2 g,tid,对照组服用丁苯肽胶囊0.02 g,tid,共4周。于治疗前和治疗后12周,采用单光子发射计算机断层成像(SPECT)方法评估狭窄侧大脑中动脉(MCA)感兴趣区(ROI)的局部脑血流量(rCBF),比较两组MCA区域rCBF和整个CBF改善的差异。结果:丁苯酞组48例(54个狭窄血管)和对照组46例(54个狭窄血管)患者完成前后2次SPECT检查,两组狭窄侧MCA区各有54×4=216个ROI区。丁苯酞组治疗后rCBF较治疗前升高[(85.8±12.5)%和(83.5±11.4)%,P=0.000],对照组治疗前后rCBF无变化[(87.8±11.7)%和(86.9±11.6)%,P=0.331]。丁苯酞组rCBF恶化、无变化和改善的ROI比例分别为6.9%,74.5%和18.5%,而对照组为20.8%,67.6%和11.6%,两组间差异显著(P=0.000)。将rCBF改善或恶化的ROI数量≥2个定义为整体CBF改善或恶化,回归分析显示丁苯酞是改善颈动脉系统狭窄患者整体脑低灌注的独立性保护因素[Wald-χ2=5.247,P=0.022,OR=3.31(1.19~9.20)]。结论:丁苯酞胶囊能够改善脑动脉粥样硬化性狭窄所致脑低灌注。

Objective: To explore the improving effect of DL-3-n-butylphthalide( NBP) on cerebral hypoperfusion caused by cerebral atherosclerotic stenosis.Methods: In this single-center, randomized, double-blind,placebo-controlled study, 120 patients with severe stenosis of the carotid artery system and cerebral hypoperfusion were included and randomly assigned into the NBP group or control group at radio of 1∶1. Patients were given NBP200 mg or NBP 20 mg capsules three times daily for four weeks. Single photon emission computed tomography(SPECT) was carried out to assess the regional CBF(rCBF) in four regions of interest(ROIs) corresponding to middle cerebral artery(MCA) ipsilateral to stenosis before and 12 weeks after the trial. The CBF change after the trial was compared between two groups.Results: 48 patients in NBP group and 46 patients in control group completed two SPECT evaluations and were included in the efficacy analysis. There were 54 stenotic arteries and216 ROIs in the MCA territory ipsilateral to stenosis, respectively, in two groups. rCBF was shown increased after the therapy(85.8% ±12.5% vs 83.5% ±11.4%,P= 0. 000) in NBP group but no change(87. 8% ± 11. 7%vs 86.9% ±11.6%,P= 0. 331) in control group. The radios of ROIs with different rCBF changes were significantly different between NBP and control groups(6. 9% vs 20. 8% for rCBF deterioration 74. 5% vs 67. 6% for rCBF stablization,18.5% vs 11.6% for rCBF amelioration,P=0. 000). When the whole CBF deterioration or amelioration was defined as the numbers of rCBF deterioration or amelioration≥2, ordinal regression analysis showed that NBP independently improved the whole CBF in the ipsilateral MCA territory in the patients with carotid arterial stenosis[Wald-χ2= 5. 247,P= 0. 022,OR = 3. 31(1. 19 ~ 9. 20)].Conclusion: NBP capsules can improve the cerebral hypoperfusion caused by cerebral artherosclerotic stenosis.