Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes

BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.

Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era

In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.

Post reperfusion syndrome during liver transplantation:From pathophysiology to therapy and preventive strategies

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A Pub Med search was conducted using the Me SH database, "Reperfusion" AND "liver transplantation" were the combined Me SH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

Heat shock protein 72 normothermic ischemia,and the impact of congested portal blood reperfusion on rat liver

INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due to the generation of reactive oxygen species(ROS)and apoptosis of cardiac muscle cells.However,many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration,such as short half-life,low stability,low bioavailability,and side effects for treatment myocardial ischemia reperfusion injury.Therefore,it is necessary to develop effective drugs and technologies to address this issue.Fortunately,nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury.Compared with traditional drugs,nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’size,shape,and material characteristics.In this review,the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed.Furthermore,we summarized the applications of ROS-based nanoparticles,highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

Effect of electroacupuncture pretreatment on adenine nucleotides in myocardial tissues of rats with myocardial ischemia-reperfusion injury detected by high performance liquid chromatography(HPLC)

Objective:To observe the effect of electroacupuncture(EA)pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury(MIRI)rats,and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats.Methods:Forty SPF male Sprague-Dawley(SD)rats were randomly divided into 5 groups:a blank group,a sham operation group,a model group,an EA at Neiguan(PC 6)group and an EA at Hegu(LI 4)group,with 8 rats in each group.Rats in the blank group only received binding to the rat plate,30 min/time,once a day for 7 d;on the 7th day,rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day,rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation,for 40 min before the blood flow was restored,and then the rats were allowed to stand for 60 min before collection of the specimens;on the 7th day of pretreatment with EA at Neiguan(PC 6)or Hegu(LI 4)for 30 min per day(once a day for 7 d),rats in the EA at Neiguan(PC 6)group and EA at Hegu(LI 4)group were subjected to modeling and sample collection same as in the model group.The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups.Hematoxylin-eosin(HE)staining and transmission electron microscope(TEM)were used to observe the changes in myocardial pathological morphology.The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography(HPLC).Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group.Compared with the model group,the myocardial injury in the EA at Neiguan(PC 6)and the EA at Hegu(LI 4)groups was mild or hardly any.The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group(all P<0.05);compared with the sham operation group,the adenine nucleotide level of the model group was also decreased,but the difference was not statistically significant(P>0.05);compared with the model group,the adenine nucleotide level in the EA at Neiguan(PC 6)group was increased(P<0.05),and the adenine nucleotide level in the EA at Hegu(LI 4)group was significantly increased(P<0.01).The adenine nucleotide level in the EA at Hegu(LI 4)group was higher than that in the EA at Neiguan(PC 6)group,but the difference was not statistically significant(P>0.05).Compared with the EA at Neiguan(PC 6)group,the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in the EA at Hegu(LI 4)group were significantly increased(all P<0.01).Conclusion:Both EA at Neiguan(PC 6)and Hegu(LI 4)can alleviate the pathological damage to myocardium in MIRI rats,and increase the adenine nucleotide level in myocardial tissues,and thus protect MIRI rats.EA at Hegu(LI 4)has a better protective effect than Neiguan(PC 6).

失血性休克后肾脏保护的研究进展

失血性抗休克是一种由于创伤等原因引起的临床常见的急危重症。尤其是肾脏在缺血缺氧后引起的局部组织灌注不足和细胞缺氧,极易导致急性肾损伤。临床上在不断探寻患者失血性休克后更安全、实用和有效的复苏方法,如从晶胶液体到高渗液体、从常压复苏到低压复苏、从纠正血压到恢复组织细胞的氧供、从维持血流动力学稳定到抑制细胞凋亡、从血管活性药到中药再到酶抑制剂的应用等等,以达到更好地保护肾脏的目的。本文就近年来关于失血性休克患者肾脏的保护研究进展进行综述。

低氧辅助治疗在心肌梗死管理中的潜力研究进展

心肌梗死仍然是一个重大的公共卫生挑战,尽管在急性期治疗和长期管理方面已经取得了进步,但寻找创新疗法以提高效果,改善患者预后及生活质量的探索仍在继续。即使目前手术治疗已经相当成熟,心肌梗死患者术后并发症发生率仍然较高,这促使医学界开始寻求辅助治疗方案。氧疗在20世纪被视为心肌梗死治疗的基石,但新证据揭示其对正常氧饱和度患者效果有限且可能带来潜在不良反应,这一治疗方法已不推荐常规使用。低氧治疗因此成为一种备受期待的新兴方法。低氧辅助治疗是通过控制性、间歇性地将患者暴露于低氧环境,引发适应性反应,从而改善心肌的代谢功能,增强血管功能,并提升运动耐力。这一疗法潜在的机理涉及稳定低氧诱导因子、刺激血管生成以及减少氧化应激,从而抵御缺血损伤,促进心脏修复。总之,低氧辅助治疗为心肌梗死管理提供了一种前景广阔的新方法,但需要通过更多的研究来优化其应用,并确保其安全性和有效性。

药物治疗在肝切除术中预防缺血再灌注损伤的研究进展

肝切除术中常采用肝门阻断和控制中心静脉压的方法减少出血,保证手术视野清晰,从而使手术顺利进行,但在肝门阻断和开放过程中会导致肝脏缺血再灌注损伤(hepatic ischemia-reperfusion injury,HIRI)、胃肠道淤血、肠源性细菌移位等问题。因此,围术期采取各种措施减轻因肝门阻断引起的HIRI进而提高手术的安全性成为肝切除术的研究热点。缺血预处理、亚低温处理、药物治疗、抗凋亡基因治疗等方法应运而生,其中药物治疗具有可操作性强、相对安全、临床上易操作等优势,因而受到广泛关注。本文对有助于改善HIRI的部分代表药物及作用机制进行总结,为HIRI的临床诊治提供参考。

基于网络药理学及计算机辅助药物设计方法分析雷诺嗪治疗心肌缺血再灌注损伤致心律失常的潜在靶点及机制

目的利用网络药理学方法和计算机辅助药物设计策略,分析雷诺嗪对心肌缺血再灌注损伤(MIRI)致心律失常的潜在治疗靶点及机制。方法采用Swiss Target Prediction数据库和DrugBank数据库预测雷诺嗪潜在的作用靶点。采用GeneCards数据库搜集MIRI和心律失常疾病的靶点,检索时间为建库至2023年1月26日,将雷诺嗪、MIRI和心律失常相关靶点进行交集比对以获取雷诺嗪治疗MIRI致心律失常的关键靶点。利用STRING数据库和Cytoscape软件绘制靶点蛋白互相作用网络。利用DAVID数据库对靶点进行信号通路富集分析。利用Cy-toscape软件构建药物-靶点-信号通路网络。利用分子对接软件验证雷诺嗪与交集靶点结合能力。最后通过分子相似性分析及分子动力学模拟研究,验证预测靶点的准确性。结果筛选获得雷诺嗪治疗MIRI致心律失常的潜在作用靶点30个。通过蛋白互相作用分析共获得8个核心靶点,包括SRC、PIK3CA、MAPK8、MAPK14、JAK1、MAP2K1、JAK2和PIK3CG。GO生物分析共筛选出177个生物学过程,其中包括123个细胞生物过程,23个细胞组成和31个分子功能。KEGG分析发现119条相关信号通路。分子对接分析结果显示,雷诺嗪与8个核心靶蛋白均具有较好的亲和力。分子相似性分析结果显示,雷诺嗪与8个核心靶蛋白原配体都存在一定相似性。分子动力学模拟了相关性最高的3个靶点(SCR、PIK3CA和MAPK8),结果显示雷诺嗪表现出MAPK8和SCR抑制剂潜力,而对PIK3CA的抑制剂位点结合潜力相对较差,结合文献复习,推测出雷诺嗪对MIRI致心律失常治疗作用的最相关分子机制。结论雷诺嗪可通过多靶点、多途径治疗MIRI致心律失常,这对促进治疗MIRI致心律失常靶向药物的研发及临床应用具有重要意义。

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

Background The traditional Chinese medicine injury, but the mechanism of its action is not we protective role of Tongxinluo. Tongxinluo can protect myocardium against documented. We examined the involvement schaemia/reperfusion of nitric oxide in the Methods Miniswine were randomized to four groups of seven： sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N^ωnitro-L-arginine （L-NNA, 10 mg/kg i.v.）. Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts

Background Our previous studies have demonstrated that Tongxinluo （TXL）, a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A （PKA）-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. Methods In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL （0.05 g/kg, gavaged one hour prior to ischemia）, and TXL ＋ H-89 （a PKA inhibitor, intravenously and continuously infused at 1.0 μg/kg per minute） groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein （p-CREB） （Ser133）, tumor necrosis factor a （TNF-a）, P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. Results TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% （P〈0.05）. TXL pretreatment increased the PKA activity and the expression of Ser133 p-CREB in the reflow and no-reflow myocardium （P 〈0.05）. TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-a and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. Conclusion PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.

焦亡在心肌缺血再灌注损伤中的作用及相关治疗药物研究进展

细胞焦亡是近几年来通过研究发现的由半胱天冬氨酸特异性蛋白酶介导Gasdermin D蛋白发挥作用,引发的新的程序性促炎类型细胞坏死,在形态和病理生理上均不同于其它形式的细胞死亡(如凋亡、坏死)。最新研究表明,细胞焦亡参与心肌缺血再灌注损伤(MIRI)。MIRI是急性心肌梗死(AMI)患者经积极血运重建后仍有较高死亡率发生的首要原因之一。部分基于细胞焦亡相关信号通路的药物,在保护心血管疾病模型中发挥了特定作用。本文主要对细胞焦亡在MIRI中的病理生理机制及相关治疗药物影响细胞焦亡并应用于MIRI防治方面进行综述。

温阳益气法干预蒽环类化疗药物心脏毒性的研究

目的探讨温阳益气法对蒽环类化疗药物心脏毒性的干预效果。方法选择2019年10月-2021年10月青岛市中医医院收治的88例使用蒽环类化疗药物(多西他赛+表柔比星+环磷酰胺)治疗2个周期后致心脏毒性患者,随机分成对照组和观察组,2组均继续采用原方案化疗2个周期,于化疗第1天开始口服辅酶Q10,对照组不予其他干预,观察组则同时予温阳益气方口服,直至化疗结束。观察比较2组入组时和继续化疗2个周期后中医证候评分(胸闷、胸痛、心悸、畏寒肢冷、下肢水肿)、心肌损伤相关指标[肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、B型钠尿肽(BNP)]、心功能指标[左室射血分数(LVEF)]、生活质量评分(EORTC QLQ-C30),记录2组继续化疗2个周期后心电图异常发生情况、临床总有效率及不良反应发生情况。结果继续化疗2个周期后,观察组胸闷、胸痛、心悸、畏寒肢冷、下肢水肿评分均明显低于入组时及同期对照组(P均<0.05),对照组各项评分与入组时比较差异均无统计学意义(P均>0.05);2组心功能及心肌损伤指标与入组时比较虽有改善,但差异均无统计学意义(P均>0.05);观察组角色功能、躯体功能、情绪功能、社会功能、认知功能及总体生活质量评分均明显高于入组时及同期对照组(P均<0.05),对照组各项生活质量评分与入组时比较差异均无统计学意义(P均>0.05);观察组心电图异常总发生率与入组时比较差异无统计学意义(P>0.05),但明显低于对照组(P<0.05),对照组心电图异常总发生率明显高于入组时(P<0.05)。观察组总有效率为93.3%(28/44),明显高于对照组的66.7%(20/44),差异有统计学意义(P<0.05);观察组不良反应发生率为34.1%(14/44),低于对照组的68.2%(29/44),差异有统计学意义(P<0.05)。结论温阳益气法能够显著减轻蒽环类化疗药物心脏毒性患者临床症状,提高患者生活质量,不会增加心电图异常发生率,且可减少不良反应。

神经调节蛋白-1在心肌缺血再灌注中的研究进展

心肌缺血再灌注损伤过程中,心肌缺血梗死会导致心肌细胞不可逆的损伤,而缺血组织恢复血流灌注时,会引起再灌注区心肌细胞及局部血管网显著地病理生理变化,这些变化共同作用可促使进一步的组织损伤。目前临床药物和介入手术等治疗方法不能有效恢复心肌梗死后心脏的功能或失活的心肌。神经调节蛋白-1不仅在心脏组织的结构完整性中发挥重要作用,还可以通过抑制炎症反应与氧化应激、促进心脏血管形成、调节心肌重构等方式减轻心肌损伤,这使人们认识到其在治疗心肌缺血再灌注中的巨大潜力。本文将对神经调节蛋白-1在心肌缺血再灌注损伤中的研究进展进行综述和展望。

冬虫夏草醇提取物对大鼠缺血再灌注过程心肌保护作用研究

目的和方法：观察冬虫夏草对缺血再灌注过程心肌保护作用。采用Ｌａｎｇｅｎｄｏｒｆ非循环式离体心脏灌流方法，与正常对照组、缺血再灌组、刺五加注射液用药组相对比，研究了冬虫夏草醇提取物对大鼠心肌缺血－再灌注过程脂质过氧化产物（ＭＤＡ）和腺嘌呤核苷酸含量的影响。结果：冬虫夏草醇提取物显著降低了再灌注心肌的ＭＤＡ水平（Ｐ＜０．０１）及显著提高了心肌中腺嘌呤核苷酸含量（Ｐ＜００１）。结论：冬虫夏草可通过改善心肌的能量代谢减少缺血再灌注损伤。

碟脉灵注射液对大鼠心肌缺血再灌注损伤的保护作用

目的:观察碟脉灵注射液(DMLI)对大鼠心肌缺血再灌注损伤的保护作用。方法:在体大鼠结扎冠状动脉前降支30 min,再灌注24 h造成心肌缺血再灌注模型,计算心肌梗死范围(MIS),测定血清天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、心肌型肌酸激酶同功酶(CK-MB)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,并测定血浆前列环素(PGI2)及血栓素A2(TXA2) 水平。结果:与再灌模型组比较,DMLI 5、10 mL·kg-1组MIS明显缩小,血清AST、LDH、CK—MB活性及 MDA含量明显降低,SOD及GSH—Px活性明显升高,血浆TXA2水平明显下降,PGI2水平及PGIz／TXA2比值明显增高。结论:DMLI对大鼠心肌缺血再灌注损伤具有明显保护作用,可能与其增强抗氧化酶活性,减少自由基对心肌的氧化损伤,纠正PGI2／TXA2失衡等机制有关。

刺五加叶皂苷对大鼠心肌缺血再灌注心律失常的影响

目的 :观察刺五加叶皂苷 (ASS)对大鼠心肌缺血再灌注心律失常的保护作用。方法 :Wistar大鼠开胸结扎冠状动脉左室支 30 m in后松扎 ,再灌注 6 0 m in建立心肌缺血再灌注模型 ,以心电图监测心律失常情况 ,并测定心肌组织超氧物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH- Px)活性 ,丙二醛 (MAD)及 Ca2 + 浓度变化。结果 :ASS5 0和 10 0 mg· kg- 1 能防止缺血再灌注室性心律失常的发生 ,缩短心律失常的维持时间 ,降低 ST段抬高的程度 ,可明显增加再灌注心肌组织中 SOD及 GSH- Px活性 ,降低 MAD及 Ca2 + 浓度。结论 :ASS对大鼠心肌缺血再灌注心律失常具有明显保护作用 ,主要与增强心肌组织的抗氧化酶活性 ,减少自由基及 Ca2 + 超负荷对心肌的氧化损伤有关。

右美托咪定预处理减轻离体大鼠心脏缺血/再灌注损伤的线粒体相关机制

目的:研究右美托咪定(dexmedetomidine,Dex)预处理对心肌缺血/再灌注(I/R)损伤的作用及其与线粒体渗透性转换孔(mPTP)和/或线粒体ATP敏感性钾通道(mitoKATP)的关系。方法:分离SD雄性大鼠心脏置于Langendorff系统行全心停灌30 min,再灌注120 min建立心肌I/R损伤模型,停灌前15 min给予Dex(10 nmol/L)处理。测定左心室动力学、再灌注期间冠脉流量及再灌注5 min时中乳酸脱氢酶(LDH)含量,实验结束测定心肌组织formazan含量以反映心肌梗死状况。结果:与正常对照组相比,I/R组明显降低了再灌注期间的左室发展压、冠脉流量及再灌注末心肌组织formazan含量,显著升高了再灌注左室舒张末压、心肌LDH渗出;Dex预处理明显改善了I/R心脏功能及心肌组织活性(P<0.01);mPTP开放剂苍术苷(20μmol/L,再灌注前给药20min)及mitoKATP抑制剂5-羟基癸酸(100μmol/L,停灌前给药20 min)可取消Dex预处理产生的抗心脏I/R损伤作用。结论:围手术期常用的辅助麻醉药Dex具有减轻离体大鼠心脏I/R损伤作用,且该心肌保护作用可能与Dex促进缺血前mitoKATP的开放,抑制再灌注早期mPTP的开放有关。

炙甘草汤有效成分及其配伍对缺血再灌离体大鼠心脏触发活动及心肌损伤的影响

目的观察炙甘草汤有效成分,包括甘草酸单铵盐、人参总皂苷、麦冬总皂苷及其配伍对缺血再灌诱发的离体大鼠心脏触发活动的影响。方法采用Langendroff非循环式离体心脏灌流,单相动作电位记录法。结果与结论炙甘草汤总提物、单个有效成分及其配伍能明显降低缺血再灌诱发的离体大鼠心脏触发活动发生率,能明显抑制再灌性心律失常的出现,对缺血再灌性心肌损伤有显著保护作用,且有效成分配伍的效应与剂量呈一定的正相关性。