Efficacy of recombinant human TNK tissue-type plasminogen activator thrombolysis combined with atorvastatin calcium in patients with acute cerebral infarction

doi:10.3760/cma.j.issn.1007-1245.2024.24.002

Abstract

Abstract:

Objective　To study the efficacy of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis combined with atorvastatin calcium in patients with acute cerebral infarction (ACI). Methods　This study was a randomized controlled trial. A total of 90 ACI patients admitted to Department of Neurology, The Third Affiliated Hospital of Xi'an Medical University from May 2021 to December 2023 were selected as the study objects. The patients were divided into a control group (45 cases) and an observation group (45 cases) by the random number table method. The control group included 23 males and 22 females, aged (51.47±7.70) years, with a body mass index (BMI) of (24.12±2.69) kg/m². The observation group included 26 males and 19 females, aged (53.18±8.45) years, with a BMI of (23.68±2.40) kg/m². The control group was treated with rhTNK-tPA thrombolytic therapy, and the observation group was treated with atorvastatin calcium based on the control group. Both groups were treated for 2 weeks and followed up for 6 months. The clinical efficacy, serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), myelin basic protein (MBP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) before and after treatment, neurological function [National Institutes of Health Stroke Scale (NIHSS) score] and motor function [Fugl-Meyer Motor Function Assessment (FMA) score] before and after treatment and 3 months after treatment, occurrence of adverse drug reactions during treatment, and prognosis (death, vascular recanalization, and intracranial hemorrhage) during follow-up were compared between the two groups. Independent sample t test, χ² test and Fisher exact probability method were used for statistical analysis. Results　The total effective rate of the observation group was higher than that of the control group [93.33% (42/45) vs. 77.78% (35/45)] (P<0.05). After treatment, the levels of serum sICAM-1, MBP, and Lp-PLA2 in the observation group were lower than those in the control group [(291.45±22.81) μg/L vs. (308.62±23.50) μg/L, (2.24±0.41) μg/L vs. (2.58±0.46) μg/L, (142.71±20.56) μg/L vs. (157.31±19.40) μg/L] (all P<0.05). After treatment and 3 months after treatment, the NIHSS scores in the observation group were lower than those in the control group, and the FMA scores were higher than those in the control group [(5.56±1.08) points vs. (5.90±1.39) points, (3.64±0.75) points vs. (3.90±0.86) points, (68.73±10.46) points vs. (62.41±9.22) points, (79.44±10.34) points vs. (73.51±9.83) points] (all P<0.05). During treatment, there was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05). After 6 months of follow-up, the vascular recirculation rate in the observation group was higher than that in the control group [95.56% (43/45) vs. 82.22% (37/45)] (P<0.05). Conclusion　rhTNK-tPA combined with atorvastatin calcium in the treatment of ACI patients can improve the clinical efficacy, serum sICAM-1, MBP, and Lp-PLA2 levels and exercise ability, and increase the vascular revascularization rate, which is safe and reliable.

Key words:

Acute cerebral infarction, Recombinant human TNK tissue-type plasminogen activator, Atorvastatin calcium, Efficacy, Serum biomarkers, Vascular recanalization

摘要：

目的　研究重组人TNK组织型纤溶酶原激活剂（rhTNK-tPA）溶栓联合阿托伐他汀钙对急性脑梗死（ACI）患者的疗效。方法　本研究为随机对照试验。选取2021年5月至2023年12月西安医学院第三附属医院神经内科收治的90例ACI患者作为研究对象，采用随机数字表法，将患者分为对照组（45例）和观察组（45例）。对照组男23例，女22例；年龄（51.47±7.70）岁；体重指数（24.12±2.69）kg/m²。观察组男26例，女19例；年龄（53.18±8.45）岁；体重指数（23.68±2.40）kg/m²。对照组采用rhTNK-tPA溶栓治疗，观察组在对照组基础上联合阿托伐他汀钙治疗。两组均连续治疗2周，随访6个月。比较两组临床疗效，治疗前后血清可溶性细胞间黏附分子-1（sICAM-1）、髓鞘碱性蛋白（MBP）和脂蛋白相关磷脂酶（Lp-PL）A2水平，治疗前后和治疗后3个月神经功能［美国国立卫生研究院脑卒中量表（NIHSS）评分］、运动功能［Fugl-Meyer运动功能评定量表（FMA）评分］，治疗期间药物不良反应发生情况，随访期间预后情况（病死、血管再通、颅内出血）。采用独立样本t检验、χ²检验和Fisher确切概率法进行统计学分析。结果　观察组治疗总有效率高于对照组［93.33%（42/45）比77.78%（35/45）］（P<0.05）。治疗后，观察组血清sICAM-1、MBP和Lp-PLA2水平均低于对照组［（291.45±22.81）μg/L比（308.62±23.50）μg/L、（2.24±0.41）μg/L比（2.58±0.46）μg/L、（142.71±20.56）μg/L比（157.31±19.40）μg/L］（均P<0.05）。治疗后和治疗后3个月，观察组NIHSS评分均低于对照组，FMA评分均高于对照组［（5.56±1.08）分比（5.90±1.39）分、（3.64±0.75）分比（3.90±0.86）分、（68.73±10.46）分比（62.41±9.22）分、（79.44±10.34）分比（73.51±9.83）分］（均P<0.05）。治疗期间，两组不良反应总发生率比较，差异无统计学意义（P>0.05）。随访6个月后，观察组血管再通率高于对照组［95.56%（43/45）比82.22%（37/45）］（P<0.05）。结论　rhTNK-tPA联合阿托伐他汀钙治疗ACI患者可提高临床疗效，改善血清sICAM-1、MBP和Lp-PLA2水平和运动能力，提高血管再通率，安全可靠。

关键词:

急性脑梗死, 重组人TNK组织型纤溶酶原激活剂, 阿托伐他汀钙, 疗效, 血清标志物, 血管再通

Zhou Meining, Liu Xiaojuan.

Efficacy of recombinant human TNK tissue-type plasminogen activator thrombolysis combined with atorvastatin calcium in patients with acute cerebral infarction [J]. International Medicine and Health Guidance News, 2024, 30(24): 4074-4078.

周美宁刘晓娟.

重组人TNK组织型纤溶酶原激活剂溶栓联合阿托伐他汀钙对急性脑梗死患者的疗效研究 [J]. 国际医药卫生导报, 2024, 30(24): 4074-4078.

References

[1] 兰翠霞,王健,王江凤,等.血清Lp-PLA2、RDW-CV、NLR值变化与急性脑梗死患者早期神经功能恶化及预后的关系[J].中国现代医学杂志,2023,33(10):12-17.DOI:10.3969/j.issn.1005-8982.2023.10.003.
[2] 韩薇,徐宇浩,于明.依达拉奉右莰醇注射液治疗急性大动脉粥样硬化型脑梗死患者的临床研究[J].中国临床药理学杂志,2023,39(3):316-319.DOI:10.13699/j.cnki.1001- 6821.2023.03.003.
[3] 曲明卫,朱兰,刘亚萍,等.神经烯醇化酶、同型半胱氨酸、超敏C-反应蛋白、血管性血友病因子水平与血栓形成致急性脑梗死的相关性分析[J].神经损伤与功能重建,2022,17(6):360-362.DOI:10.16780/j.cnki.sjssgncj.20210096.
[4] 朱明慧,张文彬,金肇权,等.伴意识障碍的缺血性脑卒中急诊血管不同再通方案的疗效比较[J].临床神经病学杂志,2020,33(2):81-84.DOI:10.3969/j.issn.1004-1648.2020. 02.001.
[5] 林兆信,陈海云,王景,等.替罗非班对急性脑梗死患者静脉溶栓后血小板参数的影响[J].中国临床药理学杂志,2023,39(16):2292-2296.DOI:10.13699/j.cnki.1001-6821.2023. 16.003.
[6] 吴松,金肇权,孙丹,等.注射用鼠神经生长因子联合注射用重组人TNK组织型纤溶酶原激活剂治疗急性脑梗死患者的临床研究[J].中国临床药理学杂志,2022,38(3):199-202.DOI:10.13699/j.cnki.1001-6821.2022.03.002.
[7] 曹晨,魏妙妙,夏晓爽,等.阿托伐他汀对急性缺血性卒中患者血小板反应性的影响[J].国际脑血管病杂志,2024,32(2):94-99.DOI:10.3760/cma.j.issn.1673-4165.2024.02.003.
[8] 叶艮英,丁少波,梁淑贞,等.丹参多酚酸盐联合阿托伐他汀钙治疗慢性肾脏病合并高脂血症的疗效观察[J].中国药物与临床,2019,19(19):3388-3390.DOI:10.11655/zgywylc2019.19.061.
[9] 中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51(9):666-682.DOI:10.3760/cma.j.issn.1006-7876.2018.09.004.
[10] 陈新东,朱志军,黄彦真,等.血清D-二聚体和超敏-C反应蛋白水平与脑梗死严重程度的相关性及脑梗死预后因素分析[J].广西医科大学学报,2017,34(3):375-378.DOI:10.16190/j.cnki.45-1211/r.2017.03.013.
[11] 赵津京,王凯,杨志丽.磁共振扩散张量成像联合Fugl-Meyer量表对老年急性脑梗死患者疗效评估的作用[J].中国脑血管病杂志,2014,(12):639-642.DOI:10.3969/j.issn.1672-5921.2014.12.005.
[12] 高东宸.药物不良反应监察指南[M].北京:中国医药科技出版社,1996:48-51.
[13] Ospel JM, Hill MD, Kappelhof M, et al. Which acute ischemic stroke patients are fast progressors?: results from the ESCAPE trial control arm[J]. Stroke, 2021, 52(5):1847-1850. DOI: 10.1161/STROKEAHA.120.032950.
[14] Tian Y, Niu HT, Li MH, et al. Effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients: a retrospective case-control study[J]. Medicine (Baltimore), 2023, 102(6):e29835. DOI: 10.1097/MD.0000000000029835.
[15] Edwards MD, Hughes TAT. Managing blood pressure in acute cerebral infarction[J]. J Neurol, 2021,268(6):2294-2296. DOI: 10.1007/s00415-021-10622-6.
[16] Zhu A, Rajendram P, Tseng E, et al. Alteplase or tenecteplase for thrombolysis in ischemic stroke: an illustrated review[J]. Res Pract Thromb Haemost, 2022, 6(6):e12795. DOI: 10.1002/rth2.12795.
[17] Xiong Y, Campbell BCV, Fisher M, et al. Rationale and design of tenecteplase reperfusion therapy in acute ischaemic cerebrovascular events Ⅲ (TRACE Ⅲ): a randomised, phase Ⅲ, open-label, controlled trial[J]. Stroke Vasc Neurol, 2024, 9(1):82-89. DOI: 10.1136/svn-2023-002310.
[18] Pan Q, Gao H, Wang Y, et al. Comparison of efficacy and safety between thrombolysis plus anticoagulation vs. anticoagulation alone for the treatment of acute submassive pulmonary embolism: a systematic review and meta-analysis[J]. Curr Vasc Pharmacol, 2022,20(6):491-500. DOI: 10.2174/1570161120666220811155353.
[19] Sanchez O, Charles-Nelson A, Ageno W, et al. Reduced-dose intravenous thrombolysis for acute intermediate-high-risk pulmonary embolism: rationale and design of the pulmonary embolism international thrombolysis (PEITHO)-3 trial[J]. Thromb Haemost, 2022, 122(5):857-866. DOI: 10.1055/a-1653-4699.
[20] Zhai Y, Wang H, Zhan S, et al. Efficacy of intravenous thrombolysis for acute severe cerebral infarction and risk factors of poor prognosis: a randomized controlled trial in 152 cases[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2021, 41(9):1426-1430. DOI: 10.12122/j.issn.1673-4254.2021. 09.20.
[21] Peng S, Xu LW, Che XY, et al. Atorvastatin inhibits inflammatory response, attenuates lipid deposition, and improves the stability of vulnerable atherosclerotic plaques by modulating autophagy[J]. Front Pharmacol, 2018, 9:438. DOI: 10.3389/fphar.2018.00438.
[22] Hossaini Nasr S, Rashidijahanabad Z, Ramadan S, et al. Effective atherosclerotic plaque inflammation inhibition with targeted drug delivery by hyaluronan conjugated atorvastatin nanoparticles[J]. Nanoscale, 2020, 12(17):9541-9556. DOI: 10.1039/d0nr00308e.
[23] Han Z, Wang Y, Li J. Effects of atorvastatin combined with nano-selenium on blood lipids and oxidative stress in atherosclerotic rats[J]. J Nanosci Nanotechnol, 2021, 21(2):1331-1337. DOI: 10.1166/jnn.2021.18633.
[24] Lee HA, Choi EJ, Park B, et al. The association between metabolic components and markers of inflammatory and endothelial dysfunction in adolescents, based on the Ewha Birth and Growth Cohort Study[J]. PLoS One, 2020, 15(5):e0233469. DOI: 10.1371/journal.pone.0233469.
[25] Vinchi F, Sparla R, Passos ST, et al. Vasculo-toxic and pro-inflammatory action of unbound haemoglobin, haem and iron in transfusion-dependent patients with haemolytic anaemias[J]. Br J Haematol, 2021, 193(3):637-658. DOI: 10.1111/bjh.17361.
[26] Wąsik N, Sokół B, Hołysz M, et al. Serum myelin basic protein as a marker of brain injury in aneurysmal subarachnoid haemorrhage[J]. Acta Neurochir (Wien), 2020, 162(3):545-552. DOI: 10.1007/s00701-019- 04185-9.
[27] Polis B, Polis L, Zeman K, et al. CSF levels of myelin basic protein in pediatric patients with ventriculoperitoneal shunt infection[J]. Cent Eur J Immunol, 2020,45(1):48-55. DOI: 10.5114/ceji.2020.94682.
[28] Fras Z, Tršan J, Banach M. On the present and future role of Lp-PLA2 in atherosclerosis-related cardiovascular risk prediction and management[J]. Arch Med Sci, 2020, 17(4):954-964. DOI: 10.5114/aoms.2020.98195.
[29] Guibbal F, Meneyrol V, Ait-Arsa I, et al. Synthesis and automated labeling of [18F]Darapladib, a Lp-PLA2 ligand, as potential PET imaging tool of atherosclerosis[J]. ACS Med Chem Lett, 2019, 10(5):743-748. DOI: 10.1021/acsmedchemlett.8b00643.
[30] Santoso A, Heriansyah T, Rohman MS. Phospholipase A2 is an inflammatory predictor in cardiovascular diseases: is there any spacious room to prove the causation?[J]. Curr Cardiol Rev, 2020,16(1):3-10. DOI: 10.2174/1573403X15666190531111932.
[31] Komatsu T, Ayaori M, Uto-Kondo H, et al. Atorvastatin reduces circulating S100A12 levels in patients with carotid atherosclerotic plaques - a link with plaque inflammation[J]. J Atheroscler Thromb, 2022, 29(5):775-784. DOI: 10.5551/jat.61630.
[32] Baganha F, de Jong RCM, Peters EA, et al. Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization[J]. Angiogenesis, 2021, 24(3):567-581. DOI: 10.1007/s10456-021-09767-9.