前列地尔对急性力竭大鼠心肌细胞缺血及凋亡的影响
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摘要
目的观察前列地尔对急性力竭大鼠心肌细胞缺血及凋亡的影响。方法将24只雄性SD大鼠(SPF级)按随机数字表法分为对照组、力竭组、低剂量前列地尔预处理力竭组(前列地尔低剂量组)、高剂量前列地尔预处理力竭组(前列地尔高剂量组)。前列地尔低剂量组、前列地尔高剂量组分别给予前列地尔5、10μg/(kg·d)腹腔注射7 d,对照组、力竭组给予0.9%NaCl 2 mL/(kg·d)腹腔注射7 d。酶联免疫吸附测定法(ELISA)检测缺血修饰白蛋白(IMA)。对大鼠心肌细胞进行TUNEL检测并观察计算凋亡指数(AI)。免疫组化法检测大鼠心肌Bax、Bcl-2含量。Western blot法检测大鼠心肌Fas、Caspase-3、Caspase-9含量。结果①力竭运动大鼠血清IMA含量显著升高。与力竭组比较,前列地尔低剂量组和前列地尔高剂量组IMA明显降低(P <0.05),且前列地尔高剂量组较前列地尔低剂量组降低更为明显(P <0.05)。②力竭运动大鼠细胞凋亡明显增多。与对照组比较,力竭组和前列地尔低剂量组AI明显升高(P <0.05)。前列地尔高剂量组与对照组比较,差异无统计学意义(P> 0.05),前列地尔高剂量组较力竭组和前列地尔低剂量组明显下降(P <0.05)。③力竭组和前列地尔低剂量组的Bax蛋白表达较对照组明显升高(P <0.05)。前列地尔高剂量组较力竭组和前列地尔低剂量组显著降低(P <0.05)。力竭组和前列地尔低剂量组的Bcl-2蛋白量较对照组显著降低(P <0.05),前列地尔高剂量组较力竭组、前列地尔低剂量组明显升高(P <0.05)。④力竭组、前列地尔低剂量组和前列地尔高剂量组的Fas、Caspase-3较对照组均显著升高(P <0.05),前列地尔高剂量组和前列地尔低剂量组较力竭组显著降低(P <0.05)。力竭组Caspase-9高于对照组(P <0.05),与力竭组比较,前列地尔低剂量组和前列地尔高剂量组Caspase-9明显降低(P <0.05)。前列地尔高剂量组Fas、Caspase-3和Caspase-9均较前列地尔低剂量组显著降低(P <0.05)。结论前列地尔可以减轻心肌细胞缺血,减少心肌细胞凋亡,对心肌细胞具有保护作用,且前列地尔对心肌细胞缺血保护及抑制凋亡的作用具有剂量依赖性。
Objective To observe the effects of Alprostadil on myocardial ischemia and apoptosis in acute exhausted rats. Methods Twenty-four male SD rats(SPF grade) were divided into control group(group C), exhausted exercise group(group E), low dose Alprostadil group(group L) and high dose Alprostadil group(group H) by random number table method. Group L and group H were respectively given intraperitoneal injection of 5 μg/(kg·d) and 10 μg/(kg·d) of Alprostadil for 7 days; and 0.9% NaCl 2 mL/(kg·d) was given intraperitoneal injection of group C and group E for 7 days. Ischemic modified albumin(IMA) was detected by enzyme-linked immunosorbent assay(ELISA). TUNEL detection of rat cardiomyocytes and the apoptosis index(AI) was calculated. The Bax and Bcl-2 in rat myocardium were detected by immunohistochemistry. The Fas, Caspase-3 and Caspase-9 in rat myocardium were detected by Western blot.Results(1)The serum IMA levels of exhausted exercise rats were significantly increased. Compared with group E, the levels of IMA of group L and group H were decreased significantly(P < 0.05). The levels of IMA of group H decreased more significantly than group L(P < 0.05).(2)Myocardial apoptosis was increased significantly after exhausted exercise.AI of group E and group L were significantly higher than group C(P < 0.05). There was no significant difference between group H and group C in AI(P > 0.05). Compared with group E and group L, AI of group H decreased significantly(P < 0.05).(3)The expression of Bax protein of group E and group L were significantly higher than that of group C(P < 0.05). Bax of group H was significantly lower than group E and group L(P < 0.05). Compared with group C, the expression of Bcl-2 protein of group E and group L significantly decreased(P < 0.05). Compared with group E and group L, Bcl-2 of group H increased significantly(P < 0.05).(4)The Fas and Caspase-3 of group E, group L and group H were significantly higher than group C(P < 0.05), while group H and group L were significantly lower than group E(P < 0.05). The Caspase-9 of group E was higher than group C(P < 0.05), compared with group E, the levels of Caspase-9 of group L and group H were significantly decreased(P < 0.05), and the levels of Fas, Caspase-3 and Caspase-9 of group H were significantly lower than group L(P < 0.05). Conclusion Alprostadil can improve myocardial ischemia, reduce cardiomyocytes apoptosis. And Alprostadil has a dose-dependent effect on myocardial ischemia and cardiomyocytes apoptosis.
Objective To observe the effects of Alprostadil on myocardial ischemia and apoptosis in acute exhausted rats. Methods Twenty-four male SD rats(SPF grade) were divided into control group(group C), exhausted exercise group(group E), low dose Alprostadil group(group L) and high dose Alprostadil group(group H) by random number table method. Group L and group H were respectively given intraperitoneal injection of 5 μg/(kg·d) and 10 μg/(kg·d) of Alprostadil for 7 days; and 0.9% NaCl 2 mL/(kg·d) was given intraperitoneal injection of group C and group E for 7 days. Ischemic modified albumin(IMA) was detected by enzyme-linked immunosorbent assay(ELISA). TUNEL detection of rat cardiomyocytes and the apoptosis index(AI) was calculated. The Bax and Bcl-2 in rat myocardium were detected by immunohistochemistry. The Fas, Caspase-3 and Caspase-9 in rat myocardium were detected by Western blot.Results(1)The serum IMA levels of exhausted exercise rats were significantly increased. Compared with group E, the levels of IMA of group L and group H were decreased significantly(P < 0.05). The levels of IMA of group H decreased more significantly than group L(P < 0.05).(2)Myocardial apoptosis was increased significantly after exhausted exercise.AI of group E and group L were significantly higher than group C(P < 0.05). There was no significant difference between group H and group C in AI(P > 0.05). Compared with group E and group L, AI of group H decreased significantly(P < 0.05).(3)The expression of Bax protein of group E and group L were significantly higher than that of group C(P < 0.05). Bax of group H was significantly lower than group E and group L(P < 0.05). Compared with group C, the expression of Bcl-2 protein of group E and group L significantly decreased(P < 0.05). Compared with group E and group L, Bcl-2 of group H increased significantly(P < 0.05).(4)The Fas and Caspase-3 of group E, group L and group H were significantly higher than group C(P < 0.05), while group H and group L were significantly lower than group E(P < 0.05). The Caspase-9 of group E was higher than group C(P < 0.05), compared with group E, the levels of Caspase-9 of group L and group H were significantly decreased(P < 0.05), and the levels of Fas, Caspase-3 and Caspase-9 of group H were significantly lower than group L(P < 0.05). Conclusion Alprostadil can improve myocardial ischemia, reduce cardiomyocytes apoptosis. And Alprostadil has a dose-dependent effect on myocardial ischemia and cardiomyocytes apoptosis.
引文
[1]马宏,田攀,李俊峡,等.力竭运动和运动预适应对大鼠心脏跨室壁复极离散度和缝隙连接蛋白43影响的研究[J].中国循证心血管医学杂志,2018,10(3):292-296.
[2]廖兴林,常芸.运动性心肌微损伤发生中凋亡基因表达谱研究[J].中国运动医学杂志,2009,28(5):510-514.
[3]汤晟凌,梁晓美,张国勇.前列地尔注射液的药理作用与临床应用进展[J].中国药房,2012,23(25):2383-2385.
[4]李公英.前列地尔联合左卡尼汀注射液治疗缺血性心肌病的短期疗效评价[J].临床合理用药,2016,6(9):62-63.
[5]张会岭,张春阳,晁英,等.前列地尔对糖尿病大鼠视网膜Bcl-2、Bax表达的影响[J].实用预防医学,2016,23(12):1519-1522.
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[9]Wei LY,Fu XH,Li W,et al.Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention[J].Chin Med J(Engl),2015,128(9):1147-1150.
[10]谢华强,杨勇,陈平英,等.前列地尔对急性冠状动脉综合征患者肿瘤坏死因子-α和基质金属蛋白酶-9的影响[J].心肺血管病杂志,2017,36(8):621-623.
[11]曹新营,王志军,杨文琦,等.前列地尔对慢性心力衰竭大鼠的血流动力学及心肌胶原纤维的影响研究[J].国际检验医学杂志,2017,38(15):2105-2108.
[12]吴建军,蔡卫华,汤卫国,等.前列地尔预处理对移植肝TNF-α和细胞凋亡的影响[J].肝胆外科杂志,2012,20(6):468-469.
[13]那世敬,李博,魏晓冬,等.参附注射液预处理联合冠脉内注射前列地尔预防ACS患者急诊PCI术后无复流现象的疗效及机制[J].现代中西医结合杂志,2018,27(12):1272-1277.
[14]赵欣.丹参多酚酸盐联合前列地尔对急性冠脉综合征患者经皮冠脉介入术后心肌微循环与心功能的影响[J].河南医学研究,2018,27(15):2806-2807.
[15]李小林,程伟宁,黄龙虎,等.前列地尔联合依达拉奉对冠心病患者心肌微循环及血液流变学的改变与疗效分析[J].中国临床医生杂志,2017,45(11):36-38.
[16]王友俊,张玲美.前列地尔对缺氧损伤的人肺微血管内皮细胞中VEGF和eNOS表达的影响[J].中国药房,2016,27(25):3518-3520.
[17]张琳琳,巴晓红.前列地尔和瓜蒌皮对大鼠心肌缺血再灌注损伤的保护作用研究[J].临床心血管病杂志,2016,32(2):123-126.
[18]刘晓玲.前列地尔联合双抗对脑梗死患者血清FIB及认知功能的影响[J].中国现代医生,2017,55(9):59-63.
[19]何赛珠,林茵,李嘉莹,等.前列地尔、长春西汀联合丹参注射液治疗脑梗死的疗效观察[J].中国医院用药评价与分析,2017,17(11):1481-1483.
[20]刘爱芬,王海宁,张晓东.前列地尔对慢性心力衰竭大鼠心肌纤维化及TGF-β1、OPG/RANKL的影响[J].临床和实验医学杂志,2017,16(16):1580-1584.
[21]魏宏,何并文,黄冰,等.前列地尔后处理对大鼠缺血再灌注心肌Bcl-2、Bax表达的影响[J].广西医学,2009,31(6):786-788.
[22]贾占伟,何强,张玉波,等.前列地尔联合针刺对噪音性耳聋大鼠耳蜗毛细胞血管内皮生长因子、Bcl-2及Bax表达的影响[J].川北医学院学报,2018,33(3):388-391.
[23]吴建军,蔡卫华,汤卫国,等.前列地尔预处理对移植肝的保护作用[J].江苏医药,2012,38(24):2944-2946.
[24]邱冬豪,赵宁,王鸣.前列地尔合并肾康片对2型糖尿病肾病患者血清TNF-α、IL-6及IL-8水平的影响[J].中国现代医生,2017,55(13):34-37.
[2]廖兴林,常芸.运动性心肌微损伤发生中凋亡基因表达谱研究[J].中国运动医学杂志,2009,28(5):510-514.
[3]汤晟凌,梁晓美,张国勇.前列地尔注射液的药理作用与临床应用进展[J].中国药房,2012,23(25):2383-2385.
[4]李公英.前列地尔联合左卡尼汀注射液治疗缺血性心肌病的短期疗效评价[J].临床合理用药,2016,6(9):62-63.
[5]张会岭,张春阳,晁英,等.前列地尔对糖尿病大鼠视网膜Bcl-2、Bax表达的影响[J].实用预防医学,2016,23(12):1519-1522.
[6]Thomas DP,Marshall KI.Effects of repeated exhaustive exercise on myocardial subcellular membrane structures[J].Int J Sports Med,1988,9(4):257-260.
[7]曹雪滨,吴学宁.运动性心脏损伤的研究进展[J].解放军医药杂志,2016,28(1):1-6.
[8]吴学宁,曹雪滨,李俊峡.基层官兵运动性心脏损伤的预警与防治[J].中国循证心血管医学杂志,2016,8(11):1396-1398.
[9]Wei LY,Fu XH,Li W,et al.Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention[J].Chin Med J(Engl),2015,128(9):1147-1150.
[10]谢华强,杨勇,陈平英,等.前列地尔对急性冠状动脉综合征患者肿瘤坏死因子-α和基质金属蛋白酶-9的影响[J].心肺血管病杂志,2017,36(8):621-623.
[11]曹新营,王志军,杨文琦,等.前列地尔对慢性心力衰竭大鼠的血流动力学及心肌胶原纤维的影响研究[J].国际检验医学杂志,2017,38(15):2105-2108.
[12]吴建军,蔡卫华,汤卫国,等.前列地尔预处理对移植肝TNF-α和细胞凋亡的影响[J].肝胆外科杂志,2012,20(6):468-469.
[13]那世敬,李博,魏晓冬,等.参附注射液预处理联合冠脉内注射前列地尔预防ACS患者急诊PCI术后无复流现象的疗效及机制[J].现代中西医结合杂志,2018,27(12):1272-1277.
[14]赵欣.丹参多酚酸盐联合前列地尔对急性冠脉综合征患者经皮冠脉介入术后心肌微循环与心功能的影响[J].河南医学研究,2018,27(15):2806-2807.
[15]李小林,程伟宁,黄龙虎,等.前列地尔联合依达拉奉对冠心病患者心肌微循环及血液流变学的改变与疗效分析[J].中国临床医生杂志,2017,45(11):36-38.
[16]王友俊,张玲美.前列地尔对缺氧损伤的人肺微血管内皮细胞中VEGF和eNOS表达的影响[J].中国药房,2016,27(25):3518-3520.
[17]张琳琳,巴晓红.前列地尔和瓜蒌皮对大鼠心肌缺血再灌注损伤的保护作用研究[J].临床心血管病杂志,2016,32(2):123-126.
[18]刘晓玲.前列地尔联合双抗对脑梗死患者血清FIB及认知功能的影响[J].中国现代医生,2017,55(9):59-63.
[19]何赛珠,林茵,李嘉莹,等.前列地尔、长春西汀联合丹参注射液治疗脑梗死的疗效观察[J].中国医院用药评价与分析,2017,17(11):1481-1483.
[20]刘爱芬,王海宁,张晓东.前列地尔对慢性心力衰竭大鼠心肌纤维化及TGF-β1、OPG/RANKL的影响[J].临床和实验医学杂志,2017,16(16):1580-1584.
[21]魏宏,何并文,黄冰,等.前列地尔后处理对大鼠缺血再灌注心肌Bcl-2、Bax表达的影响[J].广西医学,2009,31(6):786-788.
[22]贾占伟,何强,张玉波,等.前列地尔联合针刺对噪音性耳聋大鼠耳蜗毛细胞血管内皮生长因子、Bcl-2及Bax表达的影响[J].川北医学院学报,2018,33(3):388-391.
[23]吴建军,蔡卫华,汤卫国,等.前列地尔预处理对移植肝的保护作用[J].江苏医药,2012,38(24):2944-2946.
[24]邱冬豪,赵宁,王鸣.前列地尔合并肾康片对2型糖尿病肾病患者血清TNF-α、IL-6及IL-8水平的影响[J].中国现代医生,2017,55(13):34-37.