银杏蜜环口服溶液联合尼可地尔对冠心病患者血清HsCRP、HCY、IMA、LP-PLA2水平的影响

目的:研究银杏蜜环口服溶液联合尼可地尔对冠心病患者血清超敏C反应蛋白(High-sensitivity C-reactive protein,Hs CRP)、同型半胱氨酸(Homocysteine,HCY)、缺血修饰白蛋白(Ischemia Modified Albumin,IMA)和脂蛋白相关磷脂酶A2(Lipoprotein-related phospholipase A2,Lp-PLA2)水平的影响。方法:选择2016年11月～2018年11月在我院全科医学科、急诊科收治的80例冠心病患者,根据就诊顺序,用抽签法随机分为两组,每组40例患者。对照组口服尼可地尔治疗,观察组采取银杏蜜环口服溶液联合尼可地尔治疗,两组均持续治疗2周。比较两组治疗前后的血清Hs CRP、HCY、IMA、LP-PLA2水平,左室舒张末径(left ventricular end-diastolic diameter,LVEDD)、心输出量(cardiac output,CO)和左室射血分数(left ventricular ejection fraction,LVEF)等心功能指标的变化。结果:治疗后,观察组的总有效率为92.50%(37/40),明显高于对照组[75.00%(30/40)](P0.05);两组治疗后的血清Hs CRP、HCY、IMA、LP-PLA2水平均较治疗前明显降低(P0.05),且观察组以上指标均明显低于对照组(P0.05);两组治疗后的LVEDD均较治疗前明显降低,而CO和LVEF均较治疗前明显升高(P均0.05),且观察组治疗后的LVEDD与对照组相比明显降低,而CO和LVEF显著升高(P0.05)。结论:银杏蜜环口服溶液联合尼可地尔治疗冠心病的疗效明显优于单独口服尼可地尔治疗,其机制可能与降低血清Hs CRP、HCY、IMA、LP-PLA2水平相关。     

尼可地尔联合冠状动脉心脏介入治疗冠心病合并肾功能不全的疗效及对NGAL、Cys-C的影响

摘要 目的：探析冠心病（CHD）合并肾功能不全（RI）应用冠状动脉心脏介入治疗（PCI）联合尼可地尔的临床疗效及对胱抑素C（Cys-C）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）影响。方法：选择本院2019年6月~2021年6月就诊的86例CHD合并RI患者,随机数字表法分为两组各43例。 两组均实施PCI治疗,对照组实施常规静脉水化处理,观察组联合尼可地尔治疗。对比两组PCI治疗前后24 h肾功能指标（Cys-C、NGAL）、血清炎性因子指标（高敏C反应蛋白 (hs-CRP)、白细胞介素 6 (IL-6)）、心肌损伤指标（心肌肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB））、并发症发生率。结果：观察组CIN发生率（2.33%）、MACE率（2.33%）均明显低于对照组（16.28%、13.95%）,有统计学差异（P<0.05）。两组PCI治疗前Cys-C、NGAL、hs-CRP、IL-6、cTnI、CK- MB无统计学差异（P<0.05）。治疗后观察组Cys-C、NGAL、hs-CRP、IL-6升高幅度、组cTnI、CK- MB明显低于对照组（P<0.05）。结论：PCI 联合尼可地尔应用于CHD合并RI临床治疗效果显著,可有效改善患者肾功能,降低炎症反应、心肌损伤,预防CIN发生。     

尼可地尔联合盐酸曲美他嗪治疗微血管性心绞痛的临床效果和安全性分析

目的:分析尼可地尔联合盐酸曲美他嗪治疗微血管性心绞痛的临床效果和安全性。方法:选择陕西省人民医院2013年1月-2017年1月收治的微血管性心绞痛患者518例为研究对象,根据入院顺序经随机数字表法分为对照组和研究组,对照组260例患者采用盐酸曲美他嗪进行治疗,研究组258例在对照组基础上联合尼可地尔进行治疗,对比两组患者的临床总有效率、内皮血管功能和不良反应发生率。结果:治疗后,研究组的总有效率[88.76%(229/258)]显著高于对照组[62.69%(163/260)](P0.05);治疗前,两组患者的一氧化氮(NO)、内皮素(ET-1)和C-反应蛋白(CRP)水平均无差异(P0.05);治疗后,两组患者的CRP、ET-1水平均低于治疗前,且研究组低于对照组(P0.05);NO水平均高于治疗前,且研究组高于对照组(P0.05);对照组患者在治疗后的总不良反应发生率为9.23%(24/260),与研究组[10.85%(28/258)]相比差异无统计学意义(P0.05)。结论:尼可地尔联合盐酸曲美他嗪较单用盐酸曲美他嗪治疗微血管性心绞痛的效果更好,其可显著改善患者内皮血管功能,且安全性与单用盐酸曲美他嗪相当。     

Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1

Background

Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI.

冠心舒通胶囊联合尼可地尔对冠心病稳定型心绞痛心血瘀阻型患者心功能、血液流变学和炎症因子的影响

摘要 目的：观察冠心舒通胶囊联合尼可地尔在冠心病稳定型心绞痛心血瘀阻型患者中的应用价值。方法：根据随机数字表法,将广州中医药大学附属重庆北碚中医院2021年1月~2021年12月期间收治的冠心病稳定型心绞痛患者108例分为对照组（尼可地尔治疗,n=54）和观察组（冠心舒通胶囊联合尼可地尔治疗,n=54）。对比两组临床疗效、炎症因子水平、硝酸甘油片用量、西雅图心绞痛量表评分、中医证候总积分、血液流变学指标、心功能、不良反应。结果：治疗后,观察组的临床总有效率高于对照组（P<0.05）。治疗后,观察组西雅图心绞痛量表评分高于对照组,硝酸甘油片使用量少于对照组,中医证候总积分低于对照组（P<0.05）。治疗后,观察组左心室射血分数（LVEF）、心脏指数（CI）、左心室短轴缩短分数（LVFS）高于对照组（P<0.05）。治疗后,观察组全血黏度、血浆黏度及红细胞比容低于对照组（P<0.05）。治疗后,观察组白介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）、髓过氧化物酶（MPO）、C反应蛋白（CRP）水平低于对照组（P<0.05）。两组不良反应发生率组间对比,无统计学差异（P>0.05）。结论：尼可地尔与冠心舒通胶囊联合治疗可提高冠心病稳定型心绞痛心血瘀阻型患者的治疗效果,改善其心功能和血液流变学,降低炎症因子水平,具有一定临床应用价值。     

Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion

Ischemia followed by reperfusion is known to negatively affect mitochondrial function by inducing a deleterious condition termed mitochondrial permeability transition. Mitochondrial permeability transition is triggered by oxidative stress, which occurs in mitochondria during ischemia-reperfusion as a result of lower antioxidant defenses and increased oxidant production. Permeability transition causes mitochondrial dysfunction and can ultimately lead to cell death. A drug able to minimize mitochondrial damage induced by ischemia-reperfusion may prove to be clinically effective. We aimed to analyze the effects of nicorandil, an ATP-sensitive potassium channel agonist and vasodilator, on mitochondrial function of rat hearts and cardiac HL-1 cells submitted to ischemia-reperfusion. Nicorandil decreased mitochondrial swelling and calcium uptake. It also decreased reactive oxygen species formation and thiobarbituric acid reactive substances levels, a lipid peroxidation biomarker. We thus confirm previous reports that nicorandil inhibits mitochondrial permeability transition and demonstrate that nicorandil inhibits this process by preventing oxidative damage and mitochondrial calcium overload induced by ischemia-reperfusion, resulting in improved cardiomyocyte viability. These results may explain the good clinical results obtained when using nicorandil in the treatment of ischemic heart disease.     

Nicorandil inhibits TLR4/MyD88/NF-κB/NLRP3 signaling pathway to reduce pyroptosis in rats with myocardial infarction

Pyroptosis is an inflammatory cell death that regulates cardiomyocyte loss after myocardial infarction. Reports indicate that nicorandil has a strong anti-inflammatory effect and protects the myocardium from myocardial infarction. However, its relationship with pyroptosis is largely unreported. Here, we investigated to influence and mechanism of action of nicorandil on cardiomyocyte pyroptosis. Forty Sprague Dawley rats were randomly assigned to sham, MI, MI + nicorandil, and MI + nicorandil + TAK242 groups (10 per group). Myocardial infarction modeling was performed through ligation of the anterior descending branch of the left coronary artery. The function of cardiac was evaluated through echocardiography, detection of myocardial adenine nucleotides, cTnI, LDH, TTC, and HE staining. Moreover, we used qRT-PCR, immunohistochemistry, and Western blotting to examine the expression of pyroptosis-related molecules and the inflammasome pathway of TLR4/MyD88/NF-κB/NLRP3. Myocardial infarction caused the activation of GSDMD, aggravated myocardial injury, and triggered cardiac dysfunction. Myocardial infarction induced pyroptotic cell death, manifested as upregulation in mRNA and protein levels associated with pyroptosis, including caspase-1 cleavage and increased expression of IL-1β and IL-18. These changes were mitigated by nicorandil. The achieved data implicate that myocardial infarction induces pyroptosis via the TLR4/MyD88/NF-κB/NLRP3 pathway, which can be inhibited by nicorandil pretreatment. Therefore, nicorandil exerts cardioprotective effects by activating K_ATP channels, and at least in part through inhibition of the TLR4/MyD88/NF-κB/NLRP3 pathway to reduce myocardial infarction-induced pyroptosis. As such, it is a potential therapy for ischemic heart disease.     

尼可地尔对冠心病合并2型糖尿病不完全血运重建术后的疗效观察

目的:比较尼可地尔与单硝酸异山梨酯对冠心病合并2型糖尿病患者不完全血运重建术后的疗效。方法:入选112例经皮冠状动脉介入治疗(PCI)部分血运重建的冠心病合并2型糖尿病患者。随机分为2组:尼可地尔组(5 mg,3次/d,口服)60例,单硝酸异山梨酯组(50 mg,1次/d,口服)52例,两组患者均给予常规冠心病及糖尿病药物治疗。术后4周末行运动负荷试验,观察总运动时间,从开始运动到出现ST段压低1.0 mv和出现心绞痛的时间(s),以及最大ST段压低幅度,同时记录每周心绞痛发作次数及硝酸甘油用量。结果:4周后两组患者同服药前比较,从开始运动到出现ST段压低1.0 mv的时间延长,总运动时间延长,从开始运动到出现心绞痛的时间延长,最大ST段压低幅度降低(P0.01),但尼可地尔组与单硝酸异山梨酯组比较无明显统计学差异(P0.05);尼可地尔组每周心绞痛发作次数及硝酸甘油用量明显少于单硝酸异山梨酯组(P0.05)。结论:尼可地尔可增加冠心病合并糖尿病患者行不完全血运重建术后患者运动耐量,在减少心绞痛方面作用优于单硝酸异山梨酯。     

Synergistic effect of Nicorandil and Amlodipine on tissue defense system during experimental myocardial infarction in rats

The synergistic protective effect of Nicorandil (K_ATP channel opener) and Amlodipine (calcium channel blocker) on heart tissue antioxidant defense system and lipid profile were examined on isoproterenol induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg^–1 daily, i.p.) for 2 days showed significant changes in antioxidant defense system and lipid profile levels. Pretreatment with Nicorandil (2.5 mg kg^–1 daily, p.o.) and Amlodipine (5.0 mg kg^–1 daily, p.o.) for 3 days significantly prevented these alterations and restored the enzyme activities to near normal. These findings indicate the synergistic protective effect of Nicorandil and Amlodipine on tissue defense system and lipid metabolism during isoproterenol induced cardiac damage.     

Synthesis,antinociceptive activity and pharmacokinetic profiles of nicorandil and its isomers

Nicorandil (N-(2-hydroxyethyl)nicotinamide nitrate) is an antianginal drug, which activates guanylyl cyclase and opens the ATP-dependent K⁺ channels, actions that have been suggested to mediate its vasodilator activity. We synthesized nicorandil and its two isomers, which vary in the positions of the side chain containing the nitric oxide (NO) donor, and also their corresponding denitrated metabolites. The activities of these compounds were evaluated in an experimental model of pain in mice. Pharmacokinetic parameters of nicorandil and its isomers, as well as the plasma concentrations of the corresponding denitrated metabolites and also nicotinamide and nitrite were determined. Nicorandil exhibited the highest antinociceptive activity, while the ortho-isomer was the least active. Nicorandil and para-nicorandil, which induced higher plasma concentrations of nitrite, exhibited higher antinociceptive activity, which suggests that the release of NO may mediate this activity.