CN115227700B - 商陆皂苷甲在制备心肌梗死保护药物中的应用 - Google Patents
商陆皂苷甲在制备心肌梗死保护药物中的应用 Download PDFInfo
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Abstract
本发明公开了商陆皂苷甲在制备心肌梗死保护药物中的应用。商陆皂苷甲对体外缺氧损伤的HL‑1细胞具有明显地保护作用。商陆皂苷甲能有效改善由缺氧引起的HL‑1细胞内ROS水平的升高和细胞膜电位下降情况,增强细胞线粒体的抗氧化应激能力。商陆皂苷甲对心梗而引起的LDH、cTnI、CK‑MB、MDA升高具有明显的下调作用,对SOD具有明显上调作用。心电图和心脏超声结果表明商陆皂苷甲对MI引起的心脏功能损伤起保护作用,可以在一定程度上改善心梗小鼠的心脏功能。商陆皂苷甲能在一定程度保护心脏由于血管结扎造成的组织病理变化,有效减缓结扎导致的心梗进程,降低心肌纤维化程度,减少梗死面积,有效降低小鼠心梗程度,缓解心梗后的心肌缺血情况。
Description
技术领域
本发明涉及一种中药有效成分的新用途,具体涉及商陆皂苷甲在制备心肌梗死保护药物中的应用。
背景技术
心肌梗死(Myocardial infarction,MI)也称为心脏病发作,临床上常见于进入心脏的血液流量减少或停止而引发的心肌损伤,心肌梗死可能会导致心力衰竭、心律不齐、心源性休克或心脏骤停,是冠状动脉疾病最严重的表现形式。大多数心肌梗死是由于冠心病引起的,由动脉粥样硬化斑块破裂引起的冠状动脉完全阻塞通常是MI的潜在机制。因此,近年来对心梗保护药物在不断的研究和开发之中。研究发现中药对心梗具有明显的保护作用,姜黄素具有抗炎作用,可预防心肌梗死、缩小梗死面积、抑制血管周围纤维和心肌细胞凋亡。丹参酮IIA联合葛根素能有效抑制炎症细胞浸润、减轻急性缺血性心肌细胞损伤、抑制心肌纤维化、改善心肌缺血后的心脏功能。丹酚酸B通过血管生成和旁分泌机制改善MI大鼠的心脏功能。商陆皂苷甲从商陆(Phytolacca esculenta,EsA)根部分离出来的三萜皂苷,具有抗炎活性和抗氧化作用。中药商陆具有逐水消肿,解毒散结的功效,根据《太平圣惠方》卷五十四中记载商陆散能上攻心腹,治疗胸闷喘息,小便不利。EsA通过抑制氧化应激保护肝脏,慢性支气管炎、关节炎。但迄今为止,未见商陆皂苷甲在心梗保护及在制备心梗保护药物中应用的相关报道。
发明内容
本发明是发现商陆皂苷甲对心梗具有保护作用,提供一种商陆皂苷甲在制备心肌梗死保护药物中的应用。
进一步地,上述技术方案中,所述心肌梗死为急性心肌梗死。
进一步地,上述技术方案中,将商陆皂苷甲制备成单一化学成分的药物制剂,或与其他药物合用制备成复方药物制剂。
进一步地,上述技术方案中,根据药剂学相关要求和临床需要制成各种剂型应用于临床中,所述药物制剂的剂型包括:片剂、胶囊剂、注射剂、口服液体制剂、颗粒剂等。
进一步地,上述技术方案中,所述药物制剂的服用剂量为:每日口服0.8~3.25mg/kg体重。
本发明的实施例中记载了,商陆皂苷甲在制备心梗保护药物中的应用,具体给药方式为口服给药情况下,其中,小鼠口服商陆皂苷甲(10、20和40mg/kg)对心梗具有明显的保护作用,应用在临床上,推算出一个成人(60kg)每日口服约48~195mg(即0.8~3.25mg/kg体重)商陆皂苷甲对有心梗具有明显地保护作用。
进一步地,上述技术方案中,商陆皂苷甲在提高心肌细胞活力中的应用;商陆皂苷甲在降低缺氧导致的LDH上升、改善ROS水平的升高、改善细胞膜电位下降、增强细胞线粒体的抗氧化应激能力中的应用;商陆皂苷甲在下调心梗而引起的LDH、cTnI、CK-MB、MDA中的应用;商陆皂苷甲在提高体内SOD酶含量中的应用。
进一步地,上述技术方案中,商陆皂苷甲在保护心肌梗死引起的心脏功能损伤中的应用;商陆皂苷甲在保护心肌梗死引起的心脏组织病理变化、减缓心梗进程、降低心肌纤维化程度、减少梗死面积,缓解心梗后的心肌缺血中的应用。
本发明发现商陆皂苷甲具有心梗保护作用,可用于制成心梗保护药物。和缺氧组相比,商陆皂苷甲给药组细胞活力上升和LDH下降证明商陆皂苷甲对体外缺氧损伤的HL-1细胞具有明显地保护作用。商陆皂苷甲能有效改善由缺氧引起的HL-1细胞内ROS水平的升高和细胞膜电位下降情况,增强细胞线粒体的抗氧化应激能力。同时,体内实验中商陆皂苷甲对心梗而引起的LDH、cTnI、CK-MB、MDA升高具有明显的下调作用,对SOD均较模型组的降低具有明显上调作用。心电图和心脏超声结果表明商陆皂苷甲对MI引起的心脏功能损伤起保护作用,可以在一定程度上改善心梗小鼠的心脏功能。HE染色结果中,商陆皂甲给药组的细胞结构较为完整,细胞质丰富均匀、间质正常,细胞坏死数量减少,白细胞浸润程度降低。MASSON和TTC染色结果也说明商陆皂苷甲能在一定程度保护心脏由于血管结扎造成的组织病理变化,有效减缓结扎导致的心梗进程,降低心肌纤维化程度,减少梗死面积,有效降低小鼠心梗程度,缓解心梗后的心肌缺血情况。根据临床用药需求,可将商陆皂苷甲作为单一有效成分制成药物,也可与其他药物合用制成复方制剂。商陆皂苷甲具有安全(无毒副作用)、有效、经济、实用等优点。
附图说明
图1为商陆皂苷甲对HL-1细胞活力的影响。(n=6)。
图2为商陆皂苷甲对缺氧诱导HL-1细胞活性检测结果。与缺氧组比*p<0.05(n=6)。
图3为商陆皂苷甲溶液对缺氧HL-1细胞的ROS水平的影响(200×)。
图4为商陆皂苷甲对缺氧HL-1细胞线粒体膜电位的影响(200×)。
图5为商陆皂苷甲对缺氧引起HL-1细胞LDH水平的影响。与缺氧组比*p<0.05(n=6)。
图6为商陆皂苷甲对心梗小鼠心电图变化的影响。
图7为商陆皂苷甲心梗小鼠心脏超声结果的影响。A:左心室M型超声心动图;B射血分数(EF%)和短轴缩短率(FS%)测量结果。与MI组比**p<0.01,(n=8)。
图8为商陆皂苷甲对心梗组织的病理变化影响(200×)。
图9为商陆皂苷甲对心梗组织的Masson染色结果的影响(200×)。
图10为商陆皂苷甲对心梗组织心梗面积的影响。
图11为商陆皂苷甲对血清中心肌酶和氧化应激指标的影响。A:商陆皂苷甲对血清LDH、cTnI、CK-MB水平的影响;B:商陆皂苷甲对心脏脏组织MDA和SOD水平的影响与MI组比*p<0.05,**p<0.01(n=8)。
具体实施方式
下述非限制性实施例可以使本领域的普通技术人员更全面地理解本发明,但不以任何方式限制本发明。
实施例1商陆皂苷甲对缺氧心肌细胞HL-1保护作用的研究
1商陆皂苷甲对小鼠心肌HL-1细胞的细胞毒性
配置DMEM细胞培养液(内含10%FBS、100U/mL青霉素和100U/mL链霉素),复苏小鼠心肌HL-1冻存细胞,在37℃、5%CO2的环境下培养过夜,待细胞密度长至70%-80%时进行传代培养。将处于对数期生长的HL-1细胞消化,1200rpm离心5min,配制成浓度为1×105个/mL的细胞悬浮液,按照每孔100μL的细胞量接种于96孔板中,在37℃、5%CO2环境下进行培养过夜。配置不同浓度的商陆皂苷甲溶液(32、16、8、4、2、1、0.5、0.25、0.125μM),取出培养过夜的细胞将原有培养液替换为不同浓度的商陆皂苷甲溶液,每空100μL,利用CCK8法于不同时间点下(3、6、9、12、24h)分别检测细胞活力,考察不同时间点下商陆皂苷甲对HL-1细胞的毒性。用酶标仪测定在450nm处的吸光度。细胞活力计算方法如下:细胞活力(%)=[A(加药)-A(空白]/[A(0加药)-A(空白)]×100。A(加药):具有细胞、CCK8溶液和商陆皂苷甲药物溶液的孔的吸光度。A(空白):具有培养基和CCK8溶液而没有细胞的孔的吸光度。A(0加药):具有细胞、CCK8溶液而没有商陆皂苷甲药物溶液的孔的吸光度。
结果如图1所示,与Control组相比,商陆皂苷甲处理组(0.125-32μM)作用24h后HL-1细胞的存活率无统计学差异,提示商陆皂苷甲在该浓度范围内对HL-1细胞存活率无影响。结合存活率结果,将最终的药物作用时间设定为12h,浓度考察低、中、高剂量分别设定为1.6、3.2、6.4μM。
2商陆皂苷甲对缺氧HL-1细胞的保护作用
为考察不同浓度商陆皂苷甲对缺氧HL-1细胞的保护作用,将处于对数期生长的HL-1细胞进行消化,1200rpm离心5min,配制细胞悬浮液,分为Control组、模型组、给药组(1.6、3.2、6.4μM),以1×105个/mL的浓度将细胞接种于96孔板中,每孔加入100μL细胞悬浮液,在37℃、5%CO2环境下进行培养过夜后,将Control组和模型各孔培养液置换成无胎牛血清的DMEM培养液100μL,给药组各孔培养液置换为不同浓度(1.6、3.2、6.4μM)商陆皂苷甲100μL,给药12h后将模型组和给药组培养液再次置换成无葡萄糖无胎牛血清的DMEM培养液100μL,放入三气培养箱(1%O2、5%CO2、94%N2)缺氧12h,随后取出各组的细胞培养板,CCK8法检测细胞活力。
结果如图2所示,与模型组(缺氧组)相比,商陆皂苷甲给药组细胞生存率均有所升高,结果提示商陆皂苷甲可抑制缺氧诱导HL-1细胞损伤。
3商陆皂苷甲对缺氧HL-1细胞的ROS影响作用
将处于对数期生长的HL-1细胞消化,离心,重悬后以1×105个/mL的浓度接种于6孔板中,每孔2mL,同样分为Control组、模型组、给药组(1.6、3.2、6.4μM),在37℃、5%CO2环境下培养过夜。将Control组和模型组各孔培养液置换成无血清培养液1mL,给药组各孔分别孵育不同浓度商陆皂苷甲溶液1mL作用12h。随后将模型组和给药组各孔培养液置换成无葡萄糖无胎牛血清的DMEM培养液1mL,缺氧培养12h后取出,各组细胞原位装载DCFH-DA探针确定不同溶度商陆皂苷甲溶液对缺氧HL-1细胞的ROS影响作用。DCFH-DA探针用无血清的DMEM培养液按照1:1000(V/V)的比例进行稀释,加入各组6孔板中,每孔1mL,然后将各组细胞板在37℃避光条件下孵育40min。最后用无血清DMEM洗涤各孔细胞3次,以充分去除未进入细胞内的DCFH-DA,各孔加入PBS培养液,用倒置荧光显微镜进行观察并拍照。
结果如图3所示,与Control组相比,模型组(缺氧组)的ROS水平明显提高,给药后,ROS水平均有显著下降,说明商陆皂苷甲可以有效改善由缺氧引起的HL-1细胞内ROS水平的升高。
4商陆皂苷甲对缺氧HL-1细胞的线粒体膜电位的影响作用
将处于对数期生长的HL-1细胞消化,离心,重悬后以1×105个/mL的浓度接种于6孔板中,每孔2mL,同样分为Control组、模型组、给药组(1.6、3.2、6.4μM),在37℃、5%CO2环境下培养过夜。将Control组和模型组各孔培养液置换成无血清培养液,给药组各孔分别孵育不同浓度商陆皂苷甲溶液1mL作用12h。随后将模型组和给药组各孔培养液置换成无葡萄糖无胎牛血清的DMEM培养液1mL,缺氧培养12h后取出。将各组细胞培养液吸除,用PBS溶液洗涤细胞一次,加入1mL细胞培养液,然后再各自加入1mL JC-1染色工作液,充分混匀。细胞培养箱中37℃孵育30分钟。37℃孵育结束后,吸除上清,用JC-1染色缓冲液洗涤2次。加入2ml细胞培养液,在荧光显微镜观察。确定不同溶度商陆皂苷甲溶液对缺氧HL-1细胞的线粒体膜电位(JC-1)影响作用,在线粒体膜电位较高时,JC-1聚集在线粒体的基质(matrix)中,形成聚合物(J-aggregates),可以产生红色荧光;在线粒体膜电位较低时,JC-1不能聚集在线粒体的基质中,此时JC-1为单体(monomer),可以产生绿色荧光。通过JC-1从红色荧光到绿色荧光的转变可以很容易地检测到细胞膜电位的下降。
结果如图4所示,与control组相比,HL-1缺氧培养12h后,线粒体膜电位由红色转变为绿色,提示模型组(缺氧组)的细胞线粒体膜电位下降。与模型组相比,给药组的线粒体膜电位显著升高,表明商陆皂苷甲能显著改善缺氧造成的细胞膜电位下降情况,增强细胞线粒体的抗氧化应激能力。
5商陆皂苷甲对缺氧HL-1细胞的乳酸脱氢酶LDH的影响作用
将处于对数期生长的HL-1细胞消化,离心,重悬后以1×105个/mL的浓度接种于96孔板中,每孔100μL,分为Control组、模型组、给药组(1.6、3.2、6.4μM)及未经药物处理的用于后续裂解的细胞组(样品最大酶活性对照组),在37℃、5%CO2环境下培养过夜。将Control组、样品活性对照组和模型组各孔培养液置换成无血清培养液,给药组各孔分别孵育不同浓度商陆皂苷甲作用12h。随后将模型组和给药组各孔培养液置换成无葡萄糖无胎牛血清的DMEM培养液,缺氧培养12h。在预定的检测时间点前1小时,将样品最大酶活性对照组的细胞内加入LDH释放试剂10μL,反复吹打数次混匀,然后继续再细胞培养箱中孵育。到达预定时间后,将细胞培养板400g离心5min,分别取各孔的上清液120μL,加入到一新的96孔板相应孔中,随即进行样品测定。样品测定时各孔分别加入60μL LDH检测工作液。混匀,室温避光孵育30min,490nm处测定吸光度。测得的各组吸光度均减去背景空白对照孔吸光度,细胞毒性或死亡率(%)=(处理样品吸光度-样品对照孔吸光度)/(细胞最大酶活性的吸光度-对照孔吸光度)×100。
结果如图5所示,与Contol组相比,模型组(缺氧组)细胞LDH水平显著升高,提示该造模方法能造成HL-1细胞缺氧;与缺氧组相比,商陆皂苷甲给药后细胞LDH水平显著下降,提示商陆皂苷甲可以有效缓解缺氧引起的细胞损伤。
实施例2商陆皂苷甲对心肌梗死小鼠治疗作用的研究
1急性心肌梗死动物模型建立
本实验采用结扎小鼠心脏左冠状动脉(LAD),构建心肌梗死模型,由于心肌梗死手术是温度敏感性的,所以整个手术过程需要严格控温。小鼠吸入3-4%异氟烷麻醉后脱毛消毒进行备皮处理,调整小鼠右侧卧位,在左侧胸大肌下缘作一斜向小鼠左上肢的斜行皮肤切口,在切口处预先缝上线待操作完成后直接闭合皮肤切口,然后依次用镊子钝性分离胸大肌与胸小肌,看见肋骨后,用小镊子夹住肋骨,用尖嘴血管钳捅开3-4肋骨的肋间隙,垂直肋间隙分开钳尖,同时开始挤心脏,心脏挤出后,在肺动脉圆锥及左心耳中间找到心肌下行的左冠状动脉前降支,在距离左心耳下缘1.5mm处用针线结扎,进针深度约0.6mm,宽度约1mm。结扎完成后直接用尖头止血钳轻轻夹持心脏,将其塞回胸腔,此时胸大肌胸小肌会盖住胸腔开口,用止血钳轻轻夹起胸大肌,挤压胸腔排气,排出胸腔内气体。收紧预先缝在切口处的缝线以闭合皮肤切口,完成操作。小鼠恢复仰卧位,关闭麻醉系统,呼吸机维持正常通气直至待小鼠恢复正常呼吸节律。假手术组(Sham组)小鼠同样吸入3-4%异氟烷麻醉后脱毛消毒进行备皮处理,在左侧胸大肌下缘作一斜向小鼠左上肢的斜行皮肤切口,然后直接缝线闭合皮肤切口。
2实验动物分组及商陆皂苷甲给药方案
100只雄性C57BL/6小鼠,随即分成7组,其中,Sham组和商陆皂苷甲单纯给药组(40mg/kg),每组8只小鼠。模型组,商陆皂苷甲高、中、低剂量组(40、20、10mg/kg)、阳性药对照组(阿司匹林50mg/kg),每组15-16只小鼠(由于心梗手术存在一定的死亡率,至少保证每组手术成功的小鼠不少于8只)。Sham组和模型组小鼠给予0.5%CMC-Na溶液连续灌胃,给药组、单纯给药组、阳性药对照组给予不同剂量商陆皂苷甲或阿司匹林,连续灌胃7天。模型组、给药组和阳性药对照组均进行心梗造模,造模成功24h后对各组小鼠进行眼眶取血,4000rpm离心10min得到血清,-80℃保存,心脏组织保存于-80℃,用于后续实验。
3心电图检测
采用生物信号采集器检测正常小鼠及心梗24h小鼠的心电图变化。小鼠吸入3-4%异氟烷麻醉后仰卧固定,用眼科镊子提起小鼠四肢皮肤,将电极按照操作要求分别扎入四肢皮下,针尖朝向四肢,打开系统软件,采集心脏心电图信号。造模成功的心梗小鼠心电图可见明显的QRS波增宽,S-T段抬高,呈弓背向上单向曲线。
结果如图6所示,与Sham组相比,MI组心电图ST段升高,提示心梗模型结扎成功;与MI组相比,商陆皂苷甲给药组ST段均下降,提示商陆皂苷甲对MI引起的心脏功能损伤起保护作用。
4心脏超声检测
使用加拿大Visual Sonics公司Vevo 1100小动物高分辨率超声成像系统(探头频率30-MHz)进行超声心动图评估心脏功能。异氟烷吸入麻醉小鼠,调节异氟烷浓度使各组小鼠心率维持在450-550次/分钟。37℃加热板上仰卧位固定小鼠,采集胸骨旁左室长轴切面图和左室短轴M型超声图像来评估小鼠心功能。在左室短轴M型超声图像上进行数字化测量,至少取3个独立的心脏周期平均值来评估左室功能,主要指标包括射血分数(EF),短轴缩短率(FS)。
结果如图7所示,左冠状动脉前降支结扎24h后,MI组小鼠的心脏功能损伤严重,射血分数(EF)和短轴缩短率(FS)下降;商陆皂苷甲给药后能显著提升心梗小鼠心脏功能,EF和FS均有一定程度的上升,表明预防给药商陆皂苷甲可以在一定程度上改善心梗小鼠的心脏功能。
5组织切片制备及HE染色
取新鲜的心脏组织4%多聚甲醛固定24h,石蜡包埋,将修整好的蜡块置于石蜡切片机切片,厚3-4μm。切片漂浮于摊片机40℃温水上将组织展平,载玻片将组织捞起,60℃烘箱内烤片。水烤干蜡烤化后取出常温保存备用。
进行HE染色,依次将切片放入二甲苯Ⅰ20min、二甲苯Ⅱ20min、无水乙醇Ⅰ5min、无水乙醇Ⅱ5min、75%酒精5min,自来水洗。苏木素染色:切片入苏木素染液染3-5min,自来水洗,分化液分化,自来水洗,返蓝液返蓝,流水冲洗。伊红染色:切片依次入85%、95%的梯度酒精脱水各5min,入伊红染液中染色5min。脱水封片:切片依次放入无水乙醇I 5min、无水乙醇II 5min、无水乙醇Ⅲ5min、二甲Ⅰ5min、二甲苯Ⅱ5min透明,中性树胶封片。显微镜镜检,图像采集分析。图像中细胞核呈蓝色,细胞质呈红色,在镜下梗死区呈凝固性坏死,心肌细胞浆呈强的嗜伊红性,且色暗,横纹消失,核多半消失和呈固缩状,有部分白细胞浸润。
结果如图8所示,与Sham组相比,心梗组的心肌细胞浆呈强的嗜伊红性,横纹消失,心肌组织紊乱、梗死区心肌细胞消失,核多半消失和呈固缩状,有部分白细胞浸润;与MI组相比,商陆皂甲给药组的组织切片中,细胞结构较为完整,细胞质丰富均匀、间质正常,细胞坏死数量减少,白细胞浸润程度降低。表明商陆皂苷甲能在一定程度保护心脏由于血管结扎造成的组织病理变化。
6组织切片进行MASSON染色
石蜡切片脱蜡。依次将切片放入二甲苯Ⅰ20min、二甲苯Ⅱ20min、无水乙醇Ⅰ5min、无水乙醇Ⅱ5min、75%酒精5min,自来水洗。切片浸入Masson A液中浸泡过夜,自来水洗。切片入Masson B液及Masson C液等比混合的染液,浸染1min,自来水洗,1%盐酸酒精分化,自来水洗。切片入Masson D液浸染6min,自来水漂洗。Masson E液浸染1min。不水洗,稍沥干直接入Masson F液染2-30s。切片用1%冰醋酸漂洗分化,两缸无水乙醇脱水。透明封片:切片放入第三缸无水乙醇5min,二甲苯5min透明,中性树胶封片。显微镜镜检,图像采集分析。图像结果中胶原纤维呈蓝色,为心肌纤维化部分;肌纤维、纤维素和红细胞呈红色。
结果如图9所示,与Sham组相比,MI切片中部分心肌细胞消失,代之以纤维胶原沉积,胶原纤维染成蓝色;与MI组相比,商陆皂甲给药组的组织切片中,染成红色肌纤维较多,而被染成蓝色的胶原纤维显著下降,提示商陆皂苷甲能有效减缓结扎导致的心梗进程,降低心肌纤维化程度。
7新鲜心脏组织进行TTC染色
心梗24小时后的小鼠麻醉后立即取新鲜心脏,不经固定液固定,将组织直接放入OCT包埋剂-20℃速冻30min,将冻好的组织稍解冻,用莱卡新刀片手动切片,厚度2-3mm为宜,切面整齐。TTC染色:将切片放入提前37℃预热好的TTC孵育液中,放入37℃水浴锅中避光孵育30min,间隔10min轻轻摇动组织,使其均匀接触到染色液,并观察染色结果。拍照:组织成色后,加入固定液终止反应,并避光保存组织,照相机拍照。心脏组织正常区呈红色,梗死区呈苍白色。
结果如图10所示,与Sham组相比,MI组白色的梗死面积显著增多,表明结扎左冠状动脉前降支能成功建立小鼠心梗模型,造成心肌缺血;与MI组相比,商陆皂苷甲给药组的小鼠心梗面积有显著下降,提示预防给药能有效降低小鼠心梗程度,缓解心梗后的心肌缺血情况。
8血清中心肌酶及氧化应激指标检测
在心肌细胞膜完整时,cTnI不能透过细胞膜到达血液,当心肌受损时,cTnI可通过受损心肌细胞膜释放到血液中,且出现时间早,升高持续时间长,对AMI的诊断具有较高的临床价值;CK-MB作为肌酸激酶同工酶的一种,主要存在于心肌中,其浓度升高对AMI的诊断也有一定价值。LDH是乳酸脱氢酶同工酶的一型,心脏以LDH为主,AMI时,LDH也有一定程度升高,本实验通过ELISA试剂盒测定血清中LDH、cTnI和CK-MB这三种心脏损伤标志物的水平,确定心肌梗死程度。
MDA可反映机体内脂质过氧化的程度,间接地反映出细胞损伤的程度。MDA的测定常常与SOD的测定相互配合,SOD活力的高低间接反应了机体清除氧自由基的能力,而MDA的高低又间接反应了机体细胞受自由基攻击的严重程度。按照试剂盒说明书测定血清中MDA和SOD的水平共同确定心梗后机体的氧化应激水平。
结果如图11所示,与Sham组相比,MI组的心肌酶水平显著升高;与MI组相比,商陆皂苷甲给药组的心肌酶水平均有所下降,差异具有显著性意义。同时,商陆皂苷甲能有效降低有心梗引起的体内氧化应激指标MDA的升高,提高心梗小鼠体内SOD酶的含量,提示商陆皂苷甲保护MI引起的氧化损伤,降低心梗小鼠的心肌酶水平。
Claims (7)
1.商陆皂苷甲在制备心肌梗死保护药物中的应用。
2.根据权利要求1所述的应用,其特征在于:所述心肌梗死为急性心肌梗死。
3.根据权利要求1所述的应用,其特征在于:将商陆皂苷甲制备成单一化学成分的药物制剂。
4.根据权利要求3所述的应用,其特征在于:所述药物制剂的剂型包括:片剂、胶囊剂、注射剂、口服液体制剂、颗粒剂。
5.根据权利要求3所述的应用,其特征在于:所述药物制剂的服用剂量为:每日口服0.8~3.25mg/kg体重。
6.根据权利要求1所述的应用,其特征在于:商陆皂苷甲在提高心肌细胞活力中的应用;商陆皂苷甲在降低缺氧导致的LDH上升、改善ROS水平的升高、改善细胞膜电位下降、增强细胞线粒体的抗氧化应激能力中的应用;商陆皂苷甲在下调心梗而引起的LDH、cTnI、CK-MB、MDA中的应用;商陆皂苷甲在提高体内SOD酶含量中的应用。
7.根据权利要求1所述的应用,其特征在于:商陆皂苷甲在保护心肌梗死引起的心脏功能损伤中的应用;商陆皂苷甲在保护心肌梗死引起的心脏组织病理变化、减缓心梗进程、降低心肌纤维化程度、减少梗死面积,缓解心梗后的心肌缺血中的应用。
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