1、数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10754https:/ 凌2,董圣杰3,张国伟11.烟台市烟台山医院影像科(山东烟台264003)2.烟台市烟台山医院神经内科(山东烟台264003)3.烟台市烟台山医院关节外科(山东烟台264003)【摘要】目的 利用高分辨率磁共振血管壁成像(high-resolution magnetic resonance vessel wall imaging,HRMR-VWI)技术探讨芪龙胶囊联合阿托伐他汀钙等对症状性颈动脉易损斑块的疗效及对血脂水平的影响。方法 选取 202
2、0 年 3 月至 2023 年 1 月因脑缺血性单侧肢体无力于烟台市烟台山医院行颈动脉 HRMR-VWI 检查的患者,随机分为西药治疗组(对照组)和西药联合芪龙胶囊治疗组(试验组),并于 6 个月后复查,比较两组的 HRMR-VWI 测量结果及血脂水平。结果 共纳入 32 例患者,对照组 18 例、试验组 14 例。治疗后试验组甘油三酯水平显著低于对照组(1.070.38 vs.1.841.24,P=0.033)。与治疗前相比,对照组远端正常血管面积及重构指数增大,试验组最窄处管腔面积增大,两组脂核面积及甘油三酯均减小(P 0.05)。结论 芪龙胶囊联合西药治疗有显著的降脂作用,可改善颈动脉斑
3、块狭窄,并在一定程度上逆转血管重构效应。【关键词】高分辨率磁共振血管壁成像;颈动脉易损斑块;芪龙胶囊The value of HRMR-VWI in assessing the effect of Qilong capsule combined with Western medicine in the treatment of symptomatic vulnerable carotid plaque Ai-Jie WANG1,Yi-Fan HE1,Chun-Ye WANG1,Ling YU2,Sheng-Jie DONG3,Guo-Wei ZHANG11.Department of Radi
4、ology,Yantaishan Hospital,Yantai 264003,Shandong Province,China2.Department of Neurology,Yantaishan Hospital,Yantai 264003,Shandong Province,China 3.Department of Joint and Bone Surgery,Yantaishan Hospital,Yantai 264003,Shandong Province,ChinaCorresponding author:Guo-Wei ZHANG,Email:【Abstract】Object
5、ive Using high-resolution magnetic resonance vascular wall imaging(HRMR-VWI)technique to explore the efficacy of Qilong capsule combined with atorvastatin calcium and others on symptomatic vulnerable carotid plaque and the effect on lipid levels.Methods Patients who underwent carotid HRMR-VWI at Yan
6、taishan Hospital for cerebral ischemic unilateral limb weakness from March 2020 to January 2023 were selected and randomly divided into a Western medicine treatment group(control group)and a Western 数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10755https:/ combined with Qilong capsu
7、le treatment group(experimental group),and were rechecked after 6 months to compare the HRMR-VWI measurements and lipid levels of the two groups.Results A total of 32 patients were included,18 in the control group and 14 in the experimental group.Triglyceride level was significantly lower in the exp
8、erimental group than that in the control group after treatment(1.070.38 vs.1.841.24,P=0.033).Compared with pre-treatment,the distal normal vessel area and remodeling index increased in the control group,the lumen area at the narrowest point increased in the experimental group,and there was a decreas
9、e in lipid core area and triglycerides in both groups(P0.05).Conclusion Qilong capsule combined with western drug therapy has significant lipid-lowering effect,improves carotid plaque stenosis,and reverses vascular remodeling effect to some extent.【Keywords】HRMR-VWI;Vulnerable carotid plaque;Qilong
10、capsule颈动脉粥样斑块,特别是易损斑块,是引起缺血性脑血管病的独立危险因素,其主要发病机制是血管狭窄导致血流动力学改变及不稳定斑块脱落形成血栓,可能会导致偏瘫、猝死等严重后果1-2。因此,及早检测颈动脉易损斑块并干预其进展是减少脑血管意外发生的关键。高分辨率磁共振血管壁成像(high-resolution magnetic resonance vessel wall imaging,HRMR-VWI)技术可以准确评估血管管壁形态结构及内容成分,为实现个体化精准诊治提供有力支撑,为指导临床斑块的治疗干预、疗效的无创随访观察,甚至斑块的转归提供理论基础3。本研究利用 HRMR-VWI技术观察
11、芪龙胶囊联合阿托伐他汀钙、阿司匹林、依折麦布片等西药治疗症状性颈内动脉起始端易损斑块的结构、成分改变及血脂等临床指标的变化。1 资料与方法1.1 研究对象以 2020 年 3 月至 2023 年 1 月因脑缺血性单侧肢体无力在烟台市烟台山医院行颈动脉HRMR-VWI 的患者为研究对象。纳入标准:一侧肢体的脑缺血症状;无诱发心源性卒中的疾病史。排除标准:磁共振检查禁忌证;房颤史或心源性栓塞史;磁共振证实的其他脑实质疾病及血管病变。本研究患者均已知情同意,研究经烟台市烟台山医院伦理委员会批准通过(烟山伦准 2023058 号)。1.2 方法按照随机数字表法将患者分为对照组和试验组,对照组采用阿托伐
12、他汀钙、普罗布考片、依折麦布片、阿司匹林肠溶片治疗,所有药物建议长期服用。试验组在对照组基础上,加芪龙胶囊连续治疗 1 个月(1 疗程)。所有患者于治疗后6 个月复查,排除失访或检查图像不合格患者。颈动脉 HRMR-VWI 扫描方案:GE Discovery MR750 磁共振扫描仪,8 通道颈动脉表面线圈,以颈动脉分叉层面为中心,采用 3D-TOF MRA 序列、FSE 序列 T2WI 横轴位及 Cube T1WI 冠状位,并行增强扫描 CE-Cube T1WI(钆喷酸葡胺作为对比剂,高压注射器静脉注射,剂量 0.15 mmol/kg,注射速率 2 mL/s,注射完毕5 min后行增强扫描)
13、。颈动脉 HRMR-VWI 相关扫描参数见表 1。表1 颈动脉HRMR-VWI扫描参数Table 1.Carotid HRMR-VWI scanning parameters序列重复时间TR(ms)回波时间TE(ms)视野FOV(cm)矩阵层厚(mm)AX-3D-TOF MRAminimumOut of phase22.03202241.4DWI2 933 9823.01521225.0AX-FSE T2WI7 87610114.05125122.0COR-Cube T1WI800minimum20.02562560.6COR-Cube T1WI+C800minimum20.02562560.
14、6SAG-Cube T1WI+C800minimum20.02562560.6数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10756https:/ 图像由 2 名医师独立分析。易损斑块成分诊断标准包括:活动性炎症、纤维帽菲薄/缺损、大的脂质核心、内皮剥脱伴表面血小板聚集、斑块有裂隙或损伤以及严重的狭窄。次要标准包括:表面钙化斑、黄色有光泽的斑块、斑块内出血和正性重塑2,4。斑块形态学于 GE 工作站或锐科PACS上扫描多方位重建(multi-planar reformation,MPR)颈内动脉易损斑块最厚处的短轴
15、图,通过手工勾画测量最窄处管腔面积、斑块厚度、狭窄远端正常血管面积、脂核面积,计算管壁面积、重构指数、狭窄度(1-最窄处管腔直径/狭窄远端正常血管的直径)及标准化管壁指数5。典型的 HRMR-VWI 影像征象见图 1。1.3 统计分析 采用 SPSS 25 软件进行数据分析,满足正态分布的计量资料用均数和标准差(sx)表示,组间比较采用独立样本 t 检验,治疗前后比较采用配对 t 检验。计数资料用频数和百分比(n,%)表示,行卡方检验或 Fisher 确切概率检验法。以P 0.05 为差异具有统计学意义。2 结果2.1 一般情况共纳入症状责任侧颈动脉分叉处易损斑块患者 32 例,对照组 18
16、例、试验组 14 例。两组间临床资料、基础病史、斑块成分均无统计学差异(P 0.05),见表 2。2.2 磁共振指标与血脂水平治疗后,试验组甘油三酯显著低于对照组(1.070.38 vs.1.841.24,P=0.033),其他指标差异无统计学意义(P0.05)。与治疗前相比,对照组远端正常血管面积、重构指数均显著增加,脂核面积、甘油三酯显著减小(P 0.05);试验组管腔面积增加,脂核面积、甘油三酯显著减小(P 0.05),见表 3。2.3 Spearman相关分析颈动脉易损斑块磁共振各项指标与血脂指标的相关性 Spearman 秩相关结果显示,治疗后颈动脉斑块磁共振各参数差值与血脂各参数变
17、化均未发现相关性(P 0.05),见表 4。图1 颈动脉大脂质核心斑块治疗前后磁共振图Figure 1.MR images of carotid plaque with large lipid core before and after treatment注:1A-1C显示治疗前大脂质核易损斑块(箭头),纤维帽菲薄;2A-2C显示治疗后斑块,其脂质核心面积较前减小。数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10757https:/ 治疗前单侧肢体症状颈动脉斑块患者基本信息Table 2.Basic informa
18、tion of carotid plaque patients with unilateral limb symptoms before treatment项目对照组(n=18)试验组(n=14)t值P值年龄(sx,岁)63.7810.1663.509.840.0780.938性别(n,%)-0.607 女 8(44.4)6(42.9)男10(55.6)8(57.1)高血压(n,%)-0.459 无13(72.2)9(64.3)有 5(27.8)5(35.7)糖尿病(n,%)-0.255 无14(77.8)13(92.9)有 4(22.2)1(7.1)冠心病(n,%)-0.692 无17(94
19、.4)13(92.9)有 1(5.6)1(7.1)吸烟史(n,%)-0.318 无13(72.2)12(85.7)有 5(27.8)2(14.3)饮酒史(n,%)-0.624 无15(83.3)12(85.7)有 3(16.7)2(14.3)纤维帽缺损(n,%)-0.278 无 6(33.3)7(50.0)有12(66.7)7(50.0)表面钙化(n,%)-0.055 无 8(44.4)11(78.6)有10(55.6)3(21.4)斑块内出血(n,%)-0.253 无11(61.1)11(78.6)有 7(38.9)3(21.4)斑块内强化(n,%)-0.459 无 5(27.8)5(35.
20、7)有13(72.2)9(64.3)脂质核心(n,%)-0.403 无 3(16.7)1(7.1)有15(83.3)13(92.9)数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10758https:/ 治疗前后颈动脉易损斑块磁共振指标及血脂水平(sx)Table 3.MR indexes and blood lipid levels of vulnerable carotid plaque before and after treatment(sx)指标治疗前t值P值治疗后t值P值对照组(n=18)试验组(n=14
21、)对照组(n=18)试验组(n=14)管腔面积(mm2)19.1511.6215.868.30 0.8950.37818.6410.2717.777.75c 0.2650.792管壁面积(mm2)41.5522.8744.0320.39-0.3220.74944.4124.2742.7218.73 0.2150.832斑块厚度(mm)3.741.91 3.951.39-0.3460.731 3.711.87 3.931.42-0.3530.727远端正常血管面积(mm2)44.5611.9036.6610.17 1.9820.05747.0912.28b38.989.67 2.030.051重
22、构指数 1.410.47 1.690.55-1.5770.125 1.710.45b 1.640.38 0.4410.662狭窄度(%)0.720.26 0.710.21 0.0980.923 0.700.24 0.720.18-0.2580.798标准化管壁指数 0.670.16 0.720.15-0.9490.350 0.680.15 0.690.13-0.1550.878脂核面积(mm2)9.6414.8810.5311.38-0.1850.855 8.8114.18b 8.3010.74c 0.110.913甘油三酯(mmol/L)2.111.35 1.460.51 1.7040.09
23、9 1.841.24b 1.070.38c 2.2380.033a低密度脂蛋白(mmol/L)4.244.35 3.260.95 0.8240.416 3.061.34 2.820.93 0.5550.583总胆固醇(mmol/L)4.631.48 4.651.03-0.0380.97 4.391.56 4.180.77 0.4430.661注:治疗后对照组与试验组组间比较,aP0.05;对照组治疗前后组内比较,bP0.05;试验组治疗前后组内比较,cP0.05。表4 治疗后磁共振参数差值与血脂参数差值的相关性分析Table 4.Correlation analysis between MR
24、parameter difference and blood lipid parameter difference after treatment指标甘油三酯低密度脂蛋白总胆固醇r值P值r值P值r值P值管腔面积-0.0510.7830.0660.721-0.1460.426管壁面积0.1040.5700.1070.5610.0350.851斑块厚度0.1660.3620.1760.3350.0740.689远端正常血管面积0.1290.4830.0020.991-0.1930.289重构指数0.1410.4420.2050.2610.1620.375狭窄度-0.2250.2160.1170.5
25、25-0.0860.640标准化管壁指数0.1670.362-0.0850.6420.0610.739脂核面积-0.0240.895-0.0610.7410.1270.4883 讨论颈动脉斑块是一种伴随脂质沉积、炎细胞浸润、泡沫细胞形成的慢性炎症性病理过程,特别是易损斑块更是引发脑血管疾病的重要病理基础6。近年来,随着中医药的发展,致力于中西医结合治疗症状性颈动脉斑块的研究越来越多,但其观察指标多以血脂水平及临床症状为主,部分研究采用超声多普勒法测量颈动脉的内膜中层厚度、动脉粥样硬化斑块面积及积分等,缺乏较为直观、可重复的观察方法7-8。随着影像技术的快速发展,HRMR-VWI 在检查时可获得
26、颈动脉管壁的结构图像,且易于测量动脉管壁结构参数,如斑块厚度、动脉管腔面积、管壁面积、血管总面积、管壁标准化指数等,不仅能直观地评价管腔狭窄程度,还可分析斑块负担指标9-10。本研究利用HRMR-VWI 技术观察芪龙胶囊联合阿托伐他汀等西药治疗脑缺血性单侧肢体症状的责任侧颈内动脉起始端易损斑块及血脂等临床指标的变化,结果显示治疗前后斑块内各个成分未发生明显改变。这可能与纳入研究均为易损斑块、斑块成分复杂且一般病史较长而随访时间较短有关11。有研究数理医药学杂志 2023 年 10 月第 36 卷第 10 期 J.Math.Med.Oct.2023,Vol.36,No.10759https:/
27、HRMR-VWI 技术观察芪龙胶囊联合阿托伐他汀等西药治疗颈内动脉易损斑块的变化,结果显示,试验组治疗后部分观察指标发生了变化,最窄处管腔面积较治疗前增大,脂核面积减小及甘油三酯水平降低,结果提示芪龙胶囊组治疗具有一定的逆转血管重构的效果,且能够降低血脂及斑块内脂质成分,特别是甘油三酯的水平。这与之前报道芪龙胶囊辅助治疗高脂血症,且特别适用于合并高三酰甘油血症的结论一致23。综上,芪龙胶囊联合西医治疗有明显降脂作用,可改善颈动脉斑块狭窄并在一定程度上逆转血管重构效应。本研究也存在一定局限性,由于患者年龄及疫情原因,失访率较高;研究样本较小且随访时间较短。因此,芪龙胶囊联合西医治疗的降脂作用还有
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