川芎嗪对家兔主动脉损伤平滑肌细胞增殖的抑制作用

AIM: To study the inhibitory effect of ligustrazine (Lig) on growth of cultured rabbit aortic vascular smooth muscle cells (VSMC) after balloon injury. METHODS: Twenty New Zealand white rabbits were subjected to arterial injury with a balloon catheter (810 kPa for three consecutive inflations, 1 min each time). The uptake of [3H]thymidine in primary cultural VSMC incubated with rabbit serum, which obtained from the animals treated without or with Lig (40 mg.kg-1.d-1, i.v.) for 21 d (7 d before and 14 d after the injury procedure) was determined. The determination was performed in direct addition of TMP to culture as well. And histological cross-sections of the blood wall were also analyzed. RESULTS: After balloon injury the intimal thickening (77 +/- 23) microns and lumen diameter narrowing (877 +/- 118) microns in dilated sites were increased significantly than the normal adjacent wall [(41 +/- 13) microns, P < 0.01; (1033 +/- 175) microns, P < 0.05, respectively]. Treatment with Lig decreased both intimal thickening (56 +/- 16) microns (P < 0.05) and lumen diameter narrowing (1023 +/- 157) microns (P < 0.05). Lig inhibited [3H]thymidine uptake in VSMC incubated with the serum obtained from these rabbits. Direct addition of Lig inhibited [3H]thymidine uptake in cultured VSMC in a dose-dependent manner (40-4000) micrograms/well. CONCLUSION: Lig shows a pronounced inhibitory effect on VSMC proliferation after balloon injury.     

Mechanism of vascular endothelial growth factor on the prevention of restenosis after angioplasty

To evaluate the mechanism of vascular endothelial growth factor (VEGF) on the prevention of restenosis after angioplasty, the recombinant adenovirus vector containing hVEGF₁₆₅ cDNA was constructed and transfected into vascular smooth muscle cells (VSMC) in vitro. The conditioned medium containing VEGF was collected 72 h after the infection. Then, the VSMC and human umbilical vein endothelial cells (HUVEC) were divided into control group, H₂O₂-treated group and H₂O₂+ VEGF-treated group to observe the proliferation and apoptosis by water soluble tetrazolium (WST-1) method, in situ nick end labeling (TUNEL) and flow cytometry (FCM). Compared with the control and H₂O₂+ VEGF-treated groups, the absorbance (A) value of HUVEC was decreased, and apoptosis of HUVEC was significantly increased in H₂O₂-treated group. The changes of A value and apoptosis of VSMC were contrary to those of HUVEC. H₂O₂ could stimulate the proliferation of VSMC and induce the apoptosis of HUVEC, inhibit the proliferation of HUVEC and the apoptosis of VSMC and induce restenosis. VEGF could inhibit the effect of H₂O₂ on HUVEC and VSMC and prevent restenosis. These results offered further theoretical evidence for VEGF on the prevention of restenosis after angioplasty.     

Saiko-ka-Ryukotsu-Borei-To inhibits intimal thickening in carotid artery after balloon endothelial denudation in cholesterol-fed rats

Oral administration of Saiko-ka-Ryukotsu-Borei-To (SRB), a traditional Chinese formulation, dose dependently inhibited intimal thickening in carotid artery injured by balloon endothelial denudation in cholesterol-fed rats. SRB also inhibited vascular smooth muscle cell (VSMC) proliferation, which is assessed by counting the VSMCs immunoreactive with antiproliferating cell nuclear antigen (PCNA) antibody in the intimal area. VSMC proliferation is considered to play a central role in the development of intimal thickening. SRB slightly, but not significantly, reduced serum total cholesterol and low-density lipoprotein cholesterol. These results indicate that the suppressive effect of SRB on intimal thickening may result from its inhibitory effect against VSMC proliferation, but does not depend on lowering of lipid levels. The balloon injury model used in this study has similar pathological processes to restenosis after percutaneous coronary intervention (PCI). Therefore the present results may provide a new therapeutic strategy using SRB to reduce restenosis after PCI in the treatment of patients with ischemic coronary artery disease. Furthermore, since it is considered that artery restenosis after balloon injury in PCI is "accelerated atherosclerosis, " SRB may have beneficial effects in atherosclerosis that develops over a long clinical course in hyperlipidemia, diabetes, etc.     

氯吡格雷联合阿托伐他汀对颈动脉重度狭窄患者支架成形术后血小板功能及炎症因子的影响

目的 探讨颈动脉重度狭窄患者支架成形术后氯吡格雷对其血小板功能及炎症因子的影响。方法 选取120例经颈动脉支架成形术治疗的颈动脉重度狭窄患者,随机分为两组,对照组应用阿司匹林联合阿托伐他汀,观察组应用氯呲格雷联合阿托伐他汀,术前使用3～5 d,术后均连续服用3个月。观察用药后血清D-二聚体（DD）水平、纤维蛋白原（FIB）水平、炎症因子P-选择素水平以及再狭窄事件的发生率。结果 术前,两组DD及FIB水平无显著差异;术后24 h,对照组及观察组DD及FIB水平均明显升高（P<0.05）。术后1个月,两组DD及FIB水平均明显下降,但仍明显高于术前（P<0.05）。术后3个月,DD及FIB水平和术前相比,无显著差异,DD及FIB水平均在正常范围内。术后24 h、1个月、3个月,观察组DD及FIB水平均明显低于对照组,差异有统计学意义（P<0.05）。术前,两组的P-选择素对比无统计学意义,术后均明显下降,且观察组低于对照组（P<0.05）;观察组的再狭窄事件的发生率均低于对照组（P<0.05）。结论 氯吡格雷联合阿托伐他汀可抑制重度颈动脉狭窄患者术后血小板聚集预防血栓形成,降低再狭窄事件的发生率,同时可抑制炎症因子P-选择素的表达预防动脉粥样硬化。     

银杏叶胶囊联合通脉口服液治疗冠心病PCI术后再狭窄的疗效观察

目的探讨银杏叶胶囊联合通脉口服液治疗冠心病经皮冠状动脉介入术(PCI)术后再狭窄的临床疗效。方法选取2016年12月—2017年3月成都市第三人民医院收治的冠心病PCI术后患者64例,将所有患者随机分为对照组和治疗组,每组各32例。对照组口服通脉口服液,1支/次,2次/d。治疗组在对照组基础上口服银杏叶胶囊,1~2粒/次,3次/d。两组患者均连续治疗1个月。观察两组的临床疗效,比较两组的再狭窄情况。结果治疗后,对照组和治疗组的临床症状疗效的总有效率分别为78.1%、96.9%,两组比较差异有统计学意义(P0.05)。治疗后,对照组和治疗组的心电图疗效总有效率分别为71.9%、90.6%,两组比较差异有统计学意义(P0.05)。冠心病PCI术后3个月,对照组和治疗组的再狭窄率分别为12.5%、6.3%,两组比较差异有统计学意义(P0.05)。结论银杏叶胶囊联合通脉口服液治疗冠心病PCI术后再狭窄具有较好的临床疗效,能降低冠心病PCI术后再狭窄,安全性较好,具有一定的临床推广应用价值。     

Stent-based release of a selective PDGF-receptor blocker from the bis-indolylmethanon class inhibits restenosis in the rabbit animal model

Long-term success of modern therapies for myocardial ischemia is limited by restenosis, with proliferation and migration of vascular smooth muscle cells (VSMC) as key events. Since findings in recent years indicate, that the Platelet Derived Growth Factor (PDGF) is an important selective factor in mitogenic and motogenic pathways of VSMC, different concepts for reducing restenosis by inhibiting PDGF signaling have been investigated, with local delivery of small receptor kinase inhibitors looking most promising. We tested the stent-based delivery of the PDGF-receptor inhibitor D-65495, a bis(1H-2-indolyl)methanone, in the rabbit iliac artery model of restenosis. New Zealand white rabbits underwent balloon dilation of iliac arteries for implantation of D-65495-coated or non-coated (solvent, either DMSO or 90%THF / 10% DMSO) coronary stents. After 4 weeks stents were removed and neointima formation in medial and proximal/ distal stent sections was histomorphometrically and immunohistochemically analyzed.Arteries with D-65495 eluting stents showed an up to 50% reduced restenosis compared to control stents. Also, the neointimal area was reduced, but there were no significant differences in injury score. Importantly, endothelialization was similar for control stents as well as for D-65495-coated stents, suggesting absence of a general cytostatic effect of the inhibitor. The impact of D-65495 on PDGF-receptor signaling in the vessel wall was indirectly assessed by immunohistochemical staining for activated protein kinase Akt, and PCNA as a proliferation marker and revealed some reduction for the inhibitor-treated vessels. In conclusion, the application of D-65495 caused a significant decrease in neointima formation, further supporting the concept of using locally released PDGF-receptor kinase inhibitors as anti-restenotic agents.     

Etofibrate suppresses neointima formation of the ballooned common carotid artery of rats

The inhibition of neointima formation by drugs is a major goal to prevent restenosis following angioplasty. In the present study, the effect of etofibrate on blood lipids and vessel wall was investigated using a balloon injury rat model. Two weeks after ballooning the common carotid artery neointima formation was quantified by morphometric measurement of the neointimal area and cellularity in vessel cross sections, and by fluorometric evaluation of the DNA content. Etofibrate (160 mg/kg/day) had no effect on plasma triglyceride levels, but reduced serum cholesterol by about 25%. The injury-induced increase of both the neointimal area and the DNA-content was significantly inhibited by 47% (P <0.005) and 34% (P <0.05), respectively, in the drug-treated animals in comparison to the untreated control rats. The ratio of neointima and media was significantly (P < 0.001) reduced from 152.9 ± 11.6% (controls) to 82.84 ± 12.59% in the etofibrate-treated group. The cellularity (numerical profile and volume density of nuclei) in the neointima was similar in both groups. In conclusion, injury-induced neointima formation is reduced in etofibrate-treated animals, which could be due to an inhibition of smooth muscle cell proliferation.     

Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells

Baicalein (5,6,7-trioxyflavone-7-O-beta-D-glucuronide) derived from the Chinese herb Scutellaria baicalensis is well known as a lipoxygenase inhibitor. We investigated baicalein-mediated inhibitory effects on vascular smooth-muscle cell (VSMC) proliferation and intimal hyperplasia by balloon angioplasty in the rat. In vascular injury studies, baicalein significantly suppressed intimal hyperplasia by balloon angioplasty. Baicalein significantly inhibited cell proliferation via a lipoxygenase-independent pathway using [³H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT), and flow cytometry assays. At the concentrations used, no cytotoxic effect on cell culture was found. Baicalein blocks cell-cycle progression in S/G2/M phase, consistent with the cell-cycle effects, baicalein significant inhibited cyclin D1, p42/44 mitogen-activated protein kinase (MAPK), and Akt phosphorylation without change in the other cell-cycle regulatory proteins. Furthermore, baicalein attenuated serum-induced deoxyribonucleic acid (DNA) binding activity of nuclear factor kappa B (NF-κB). These results show that baicalein blocks cell proliferation via blocking cell-cycle progression and proliferating events, including p42/44 MAPK and Akt activations as well as NF-κB activation. It also inhibits intimal hyperplasia after balloon vascular injury in the rat, indicating the therapeutic potential for treating restenosis after arterial injury. C.-Y. Peng and Y.-W. Huang contributed equally to this work.     

Artemisinin inhibits tumour necrosis factor‐α‐induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury‐induced neointima formation in rats

The aim of this study was to evaluate the effect of artemisinin (ART) on rat vascular smooth muscle cell (VSMC) proliferation induced by tumour necrosis factor (TNF)‐α, cell cycle arrest, and apoptosis, and its effect on neointima formation after balloon injury of rat carotid artery. Primary rat VSMC were identified by immunofluorescence assay. The proliferation of VSMC induced by TNF‐α was significantly inhibited by ART treatment in a dose‐dependent manner. Treatment with 100‐μM ART significantly reduced the expression of proliferating cell nuclear antigen. In contrast, the same treatment arrested the cell cycle in G0/G1 phase. Western blot analysis showed that the cell cycle‐related proteins cyclin D1, cyclin E, cyclin‐dependent kinase 2, and cyclin‐dependent kinase 4 were downregulated by ART in TNF‐α‐stimulated VSMC. For apoptosis induced by ART, cleaved caspase‐3/‐9 was detected, and the pro‐apoptotic protein Bcl‐2‐associated X protein was upregulated while the anti‐apoptotic protein Bcl‐2 was downregulated. The results suggest that ART can effectively inhibit the proliferation of VSMC induced by TNF‐α through the apoptotic induction pathway and cell cycle arrest. Also, balloon injury indicated that ART significantly inhibited neointima formation in the rat carotid arteries.     

阿加曲班和低分子肝素治疗下肢动脉硬化闭塞症合并血栓的疗效比较

目的比较阿加曲班和低分子肝素治疗下肢动脉硬化闭塞症合并血栓的临床疗效。方法选取2017年1月—2017年9月在中国医科大学附属第一医院治疗的下肢动脉硬化闭塞症合并血栓患者60例,随机分为对照组(30例)和治疗组(30例)。两组患者给予基础溶栓治疗,经溶栓导管泵入注射用尿激酶,20~40万U加入到生理盐水中配成100 m L溶液,50 m L/h,2次/d。对照组患者在基础溶栓的基础上皮下注射低分子肝素钙4 100 AXa IU,2次/d;治疗组患者在基础溶栓的基础上经溶栓导管泵入阿加曲班注射液,40 mg加入到生理盐水320 m L中,20 m L/h,1次/d。两组患者均连续治疗7 d。评价两组患者临床疗效,同时比较治疗前后两组患者踝肱指数(ABI)、跛行距离和D-二聚体水平以及并发症和不良反应。结果治疗后,对照组和治疗组的总有效率分别为73.33%、93.33%,两组比较差异有统计学意义(P0.05)。两组患者的ABI和跛行距离均显著升高,同组治疗前后差异具有统计学意义(P0.05);且治疗组的跛行距离显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗第7天,两组患者的D-二聚体水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗第3天,治疗组的D-二聚体水平较治疗前显著降低,且显著低于对照组,两组比较差异具有统计学意义(P0.05)。对照组和治疗组的并发症发生率分别为6.67%、3.33%,两组比较差异有统计学意义(P0.05)。对照组和治疗组的不良反应发生率分别为13.33%、0,两组比较差异有统计学意义(P0.05)。结论阿加曲班联合尿激酶经导管溶栓治疗下肢动脉粥样硬化闭塞症合并血栓疗效显著,能明显改善相应症状,同时具有更好的安全性。     

阿加曲班和尤瑞克林治疗进展性脑梗死的比较研究

目的比较阿加曲班注射液和注射用尤瑞克林治疗早期急性进展性脑梗死的有效性、安全性。方法选取2018年1月-2019年5月在通辽市医院住院并在发病72 h内进展的92例急性脑梗死患者,随机分成阿加曲班组和尤瑞克林组,每组各46例。阿加曲班组静脉泵入阿加曲班注射液,60 mg/d治疗2 d,然后10 mg/d治疗5 d,早晚各1次,每次持续3 h。尤瑞克林组静脉滴注注射用尤瑞克林0.15 PNA单位/d,前15 min内控制滴速。两组连续治疗14 d。观察两组患者临床疗效,同时比较治疗前后两组患者美国国立卫生研究院卒中量表(NIHSS)评分和Barthel指数评定量表(BI)评分。结果治疗后,阿加曲班组临床有效率为82.6%,显著高于尤瑞克林组的69.6%,两组比较差异有统计学意义(P<0.05)。阿加曲班组在治疗7、14d后NIHSS评分较治疗前明显降低(P<0.05),而尤瑞克林组在治疗14d后才显示出明显改善(P<0.05);治疗后阿加曲班组NIHSS评分显著低于尤瑞克林组同期,两组比较差异具有统计学意义(P<0.05)。阿加曲班组在治疗7、14 d后BI分值明显升高(P<0.05),而尤瑞克林组则在治疗14 d后与治疗前比较才显示出显著差异(P<0.05);治疗后阿加曲班组BI分值显著高于尤瑞克林组同期,两组比较差异具有统计学意义(P<0.05)。结论阿加曲班注射液治疗进展性脑梗死早期进展患者有较好的临床疗效,安全性好。     

Suppression of cyclic coronary flow variation and reduction of restenosis with abciximab for morphologically high-risk lesions undergoing percutaneous coronary intervention

Cyclic coronary flow variation (CCFV), a phenomenon related to repetitive accumulation of platelet aggregates at sites with endothelial injury, was reported to predict the acute ischemic complication after percutaneous coronary intervention. Platelet activation also stimulates neointimal proliferation, which is essential in the late restenosis process. Abciximab, a nonspecific antagonist to the platelet membrane glycoprotein IIb/IIIa as well as other integrins, may eliminate CCFV. A randomized study was conducted to evaluate the effect of abciximab on CCFV and restenosis in morphologically high-risk lesions. Forty-six coronary arteries with objective ischemia on the corresponding vascular territories were successfully treated. The use of abciximab successfully suppressed the occurrence of CCFV (p < or = 0.001) after balloon dilatation. In the follow-up study 3 months later, the use of abciximab predicted a lower loss index and less clinical recurrence (p = 0.008 and 0.03, respectively). The occurrence of CCFV, however, did not affect the angiographic or clinical outcome. The reduction of restenosis and clinical recurrence by the use of abciximab may thus be related to its nonglycoprotein IIb/IIIa effects, in addition to platelet inhibition.     

Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression

The therapeutic potential of low molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed was investigated on vascular smooth muscle cell (VSMC) and human vascular endothelial cell (HUV-EC-C) proliferation and migration in vitro and in a rat model of intimal hyperplasia. Sprague–Dawley rats were subjected to balloon injury in the thoracic aorta followed by two weeks’ treatment with either LMWF (5 mg/kg/day) or vehicle. Morphological analysis and proliferating cell nuclear antigen immunostaining at day 14 indicated that LMWF prevented intimal hyperplasia in rat thoracic aorta as compared with vehicle (neo-intima area, 3 ± 0.50 mm² versus 5 ± 0.30 mm², P < 0.01). In situ zymography showed that LMWF significantly decreased the activity of matrix metalloproteinase (MMP)-2 in the neo-intima compared to vehicle. The in vitro study demonstrated that 10 μg/ml LMWF increased HUV-EC-C migration by 45 ± 5% but reduced VSMC migration by 40 ± 3%. LMWF also increased MMP-2 mRNA expression in HUV-EC-Cs and reduced it in VSMCs. MMP-2 level in the conditioned medium from cells incubated with 10 μg/ml LMWF was 5.4-fold higher in HUV-EC-Cs, but 6-fold lower in VSMCs than in untreated control cells. Furthermore, decreasing MMP-2 expression in HUV-EC-Cs or VSMCs by RNA interference resulted in reduced LMWF-induced effects on cell migration.In conclusion, LMWF increased HUV-EC-C migration and decreased VSMC migration in vitro. In vivo, this natural compound reduced the intimal hyperplasia in the rat aortic wall after balloon injury. Therefore, LMWF could be of interest for the prevention of intimal hyperplasia.     

亚硝基乙酰青霉胺抑制人血管平滑肌细胞增殖的实验研究

目的探讨亚硝基乙酰青霉胺对人血管平滑肌细胞(VSMC)增殖的抑制作用。方法将不同浓度的亚硝基乙酰青霉胺300、500、800、1000μmol/L作用于体外培养的血管平滑肌细胞(VSMC),采用氚-胸腺嘧啶核苷(3H-TdR)掺入的方法检测细胞的增殖。结果在500、800、1000μmol/L的亚硝基乙酰青霉胺作用下,VSMC的3H-TdR掺入量cpm分别为1096.33±85.60、852.00±57.80、693.00±49.60,均与对照组的1270.00±96.50有显著性差异(P<0.01),并表现为剂量依赖性(P<0.01)。结论亚硝基乙酰青霉胺能够抑制人VSMC的增殖,可能有防治经皮腔内冠状动脉成形术后再狭窄的作用。     

巴曲酶联合阿加曲班治疗下肢深静脉血栓的疗效观察

目的探讨巴曲酶联合阿加曲班治疗下肢深静脉血栓的临床疗效。方法选取2013年1月—2016年3月在天津市第五中心医院接受治疗的下肢深静脉血栓患者98例,随机分成对照组和治疗组,每组各49例。对照组患者静脉滴注阿加曲班注射液,前2 d,15 mg加入生理盐水100 mL,1次/d,第3天5 mg加入生理盐水150 mL,2次/d。治疗组在对照组的基础上静脉滴注巴曲酶注射液,20 U加入生理盐水100 mL,1次/d。两组患者均连续治疗7 d。评价治疗前后两组患者临床疗效、患肢深静脉通畅度和视觉痛觉评分(VAS)以及消肿率差异。结果治疗后,对照组和治疗组总有效率分别为75.51%和97.96%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患肢深静脉通畅度评分显著升高,VAS评分显著降低,同组比较差异具有统计学意义(P0.05);且治疗组患者上述两项评分均明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者消肿率明显高于对照组,两组比较差异具有统计学意义(P0.05)。结论巴曲酶联合阿加曲班治疗下肢深静脉血栓疾病疗效显著,具有一定的临床推广应用价值。     

阿加曲班与急性轻中度缺血性脑卒中早期神经系统功能改变的相关性研究

目的 探讨阿加曲班对轻中度急性缺血性脑卒中患者的早期神经功能恢复的改善情况;并对不同卒中亚型的疗效进行比较,对阿加曲班疗效的影响因素进行相关性分析。方法 根据纳入及排除标准收集2019年12月1日—2021年6月1日新疆军区总医院收治的急性非心源性轻中度急性缺血性脑卒中患者,按照患者是否使用阿加曲班治疗作为分组的依据,390例入选患者分为阿加曲班组（285例）和未使用阿加曲班的对照组（105例）,收集两组患者性别、年龄、高血压、糖尿病、冠心病、既往卒中史、吸烟史等基线资料,收集治疗前后患者低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、三酰甘油（TG）、总胆固醇（TC）、抗血小板药物使用情况、入院时及治疗7 d时美国国家卫生研究院卒中量表（NIHSS）评分和改良Rankin量表（mRS）评分及卒中病因分型等数据。卒中分型诊断标准按中国缺血性卒中亚型（CISS）分型。以住院第7天时NIHSS评分和mRS评分为疗效指标,进行相关性分析。结果 阿加曲班组与对照组患者年龄,高血压、糖尿病、既往卒中、冠心病患病人数,吸烟史,LDL-C、HDL-C、TC、TG水平,入院时NIHSS评分,服用抗血小板药物种类等基线资料组间比较,差异均无统计学意义（P＞0.05）,两组间治疗7 d时NIHSS评分、治疗7 d时NIHSS评分变化、治疗7 d时mRS评分、大动脉粥样硬化型例数、穿支动脉病变型例数差异有统计学差异（P＜0.05）,在大动脉粥样硬化型亚组中,两组间年龄、入院时NIHSS评分、治疗7 d时NIHSS评分变化差异有统计学意义（P＜0.05）;在穿支动脉病变型亚组中,两组间入院时NIHSS评分、治疗7 d时NIHSS评分差异有统计学意义（P＜0.05）,治疗7 d时NIHSS评分改变与使用阿加曲班呈正相关,差异有统计学意义（P＜0.05）;患有高血压与治疗7 d时NIHSS评分,冠心病史、LDL-C水平与治疗7 d时mRS评分均呈正相关,差异有统计学意义（P＜0.05）;既往卒中病史与治疗7 d时NIHSS评分改变呈负相关,差异有统计学意义（P＜0.05）。结论 阿加曲班可以改善非心源性轻中度急性缺血性脑卒中患者的早期预后,卒中分型、合并高血压、冠心病史、既往卒中病史等因素对阿加曲班疗效有影响。     

高出血风险患者连续性肾脏替代治疗期间采用阿加曲班和枸橼酸钠抗凝治疗的对比研究

目的 评估小剂量阿加曲班与枸橼酸钠在高出血风险患者连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)中的抗凝效果及安全性。方法 前瞻性收集125例患者分为枸橼酸钠组(n=53)和阿加曲班组(n=72)。比较2组CRRT滤器寿命、凝血功能指标、滤器及管路凝血事件、血栓事件、出血事件、CRRT参数及临床指标情况。结果 阿加曲班组治疗后的凝血酶原时间、国际标准化比值、活化部分凝血活酶时间与枸橼酸钠组相比均有延长(P<0.05)。2组的凝血事件差异无统计学意义，但是枸橼酸钠组的静脉壶无凝血比例高于阿加曲班组(P<0.05)，滤器寿命也更长(P<0.05)。枸橼酸钠组总不良反应发生率高于阿加曲班组(P=0.001)。2组发生滤器凝血事件的血流量和超滤率均低于未发生滤器凝血事件的血流量和超滤率(P<0.05)。结论 枸橼酸钠在CRRT中的抗凝效果更具优势，但阿加曲班安全性更好，对于低血流量和低超滤率的CRRT宜增加阿加曲班抗凝剂量。     

阿加曲班联合低分子肝素对次大面积肺栓塞患者影像学指标及血清D-二聚体和内皮素-1水平的影响

目的 探讨阿加曲班联合低分子肝素对次大面积肺动脉栓塞患者影像学指标及血清D-二聚体和内皮素-1（ET-1）水平的影响。方法 本研究为回顾性研究,选取2019年1月—2020年12月河南省人民医院收治的68例次大面积肺动脉栓塞患者为研究对象,根据治疗方法分为对照组（n=34）和观察组（n=34）。在常规治疗的基础上,对照组患者sc低分子肝素钠5 000 IU/次,12 h给药1次。观察组在给予低分子肝素钠的基础上给予阿加曲班注射液,起始60 mg阿加曲班加入生理盐水注射液稀释至50 mL,持续48 h静脉泵入,后予10 mg阿加曲班加入生理盐水注射液稀释至30 mL,持续3 h静脉泵入,2次/d,两组均连续治疗2周。比较两组治疗前后的影像学指标变化,测定治疗前后两组患者血清D-二聚体和ET-1水平,观察两组患者治疗期间出血不良事件的发生情况。结果 与治疗前比较,治疗2周后两组患者影像学结果测定的阻塞指数（OI）和灌注指数均（PI）较明显下降（P<0.05）,观察组患者OI和PI较对照组下降的更为明显（P<0.05）;治疗7 d后,两组患者血清D-二聚体和ET-1水平较治疗前明显下降（P<0.05）,且观察组较对照组在治疗后降低的更为明显（P<0.05）。两组治疗期间出血不良事件的发生率比较无统计学意义（P>0.05）。结论 阿加曲班联合低分子肝素治疗次大面积肺动脉栓塞能加强抗凝疗效,促进血栓溶解,保护肺动脉血管内皮功能,改善预后。     

Aminoguanidine induces constrictive vascular remodeling and inhibits smooth muscle cell death after balloon injury.

We examined the effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, in the rat model of balloon injury. Arteries were assessed by histomorphometry, and vascular smooth muscle cell death and proliferation were examined 24 h and 14 days after balloon injury by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA and expression of proliferating cell nuclear antigen, respectively. Aminoguanidine decreased the luminal area 14 days after balloon injury (0.19+/-0.04 mm2 vs. 0.35+/-0.02 mmr2; P < 0.005), and this effect was attributable to reduction of the total vessel area, i.e., constrictive vascular remodeling (0.42+/-0.03 mm2 vs. 0.55+/-0.03 mm2; P < 0.005). At 24 h after injury, the percentage of TUNEL-positive cells in the medial layer was reduced by aminoguanidine (2.0+/-1.0% vs. 17.3+/-5.4%; P < 0.05), and the percentage of proliferating cells was increased (18.4+/-5.5% vs. 4.9+/-2.2%; P < 0.05). Aminoguanidine did not influence the density of VSMC nuclei in the injured artery wall, systemic blood pressure or endothelium-dependent vasorelaxation. We conclude, that in the rat model of balloon injury, aminoguanidine induces luminal loss by constrictive vascular remodeling in association with reduced early VSMC death and increased proliferation.     

阿加曲班联合阿替普酶治疗急性缺血性脑卒中的临床疗效及安全性研究

目的 探讨阿替普酶联合阿加曲班治疗急性缺血性脑卒中的治疗效果以及风险性。方法 采用回顾性分析方法,选取2019年6月－2020年6月邢台市第三医院收治的在溶栓时间窗的急性缺血性脑卒中患者100例作为研究对象,根据治疗方法将患者分为对照组（n=50）和观察组（n=50）。两组患者均给予常规基础治疗,对照组给予注射用阿替普酶静脉溶栓治疗,按照0.9 mg/kg（最大剂量为90 mg）给药,其中10%于1 min内静脉推注完毕,其余90%药液在1 h内静脉泵入。溶栓24 h后复查头颅CT无出血后,给予阿司匹林治疗。观察组在对照组基础上加用阿加曲班注射液治疗,第1～2天予以60 mg/d阿加曲班稀释后持续静脉泵注（速度2.5 mg/h）,其后阿加曲班注射液10 mg于生理盐水20 mL中持续静脉泵入3 h,2次/d。两组均持续治疗7 d。记录两组患者治疗前及溶栓后1 h、治疗后7 d、治疗后3个月的美国国立卫生研究院卒中量表（NIHSS）评分以及治疗前及治疗后3个月改良Rankin量表（mRS）评分,记录治疗期间不良反应发生情况。结果 治疗后,观察组总有效率为90.0%,显著高于对照组的74.0%（P<0.05）。治疗后,两组NIHSS、mRS评分均改善,观察组治疗后3个月NIHSS评分和mRS评分均显著低于对照组（P<0.05、0.01）。两组治疗期间不良反应总发生率比较差异无统计学意义。结论 阿替普酶联合阿加曲班治疗急性缺血性脑卒中临床效果显著,能有效减轻患者神经功能受损症状,提高生活质量且安全性良好,值得临床应用推广。