化瘀祛痰方对急性心肌缺血大鼠心肌组织RhoA、ROCK1 mRNA表达的影响
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摘要
【目的】观察化瘀祛痰方对急性心肌缺血大鼠心肌组织RhoA/Rho相关卷曲螺旋形成蛋白激酶1(ROCK1)信号通路中RhoA、ROCK1 mRNA表达的影响,探讨其防治机制。【方法】将60只SPF级雄性SD大鼠随机分为6组,即空白组,模型组,西药组,中药低、中、高剂量组,每组10只。西药组予以单硝酸异山梨酯水溶液(剂量为3.125 mg·kg~(-1)·d~(-1))灌胃,中药低、中、高剂量组予以化瘀祛痰方水煎液(剂量分别为10.4、20.8、41.6 g·kg~(-1)·d~(-1))灌胃,空白组和模型组予以等体积生理盐水灌胃,给药7 d。预灌胃7 d后,除正常组外,其余各组大鼠给予腹腔注射异丙肾上腺素(Iso)复制急性心肌缺血模型。观测大鼠心电图ST段总偏移值。采用苏木素—伊红(HE)染色法观察大鼠心肌组织结构,酶联免疫吸附分析(ELISA)检测血清内皮素1(ET-1)含量,qPCR法检测心肌组织RhoA、ROCK1 mRNA的表达。【结果】与空白组比较,模型组心肌纤维大片断裂,间质出现明显出血,心电图ST段偏移值、血清ET-1含量、心肌组织RhoA与ROCK1 mRNA表达水平均升高(P<0.05);与模型组比较,各给药组心肌纤维断裂情况改善,间质出血减少,心电图ST段偏移值、血清ET-1含量、心肌组织RhoA与ROCK1的mRNA表达水平均降低(P<0.05)。【结论】化瘀祛痰方可改善心肌缺血状态,其机制可能与降低心肌组织RhoA、ROCK1 mRNA表达,从而抑制心肌收缩,改善心肌血流量有关。
Objective To observe the effect of Stasis-resolving and Phlegm-expelling Recipe on the mRNA expression of RhoA and Rho-associated coiled-coil forming protein kinase 1(ROCK1)in myocardial tissues of acute myocardial ischemia rats,to explore its preventive mechanism. Methods Sixty SD rats were divided into blank group, model group, western medicine group, and lowgroups, 10 rats in each group. The western medicine group was given intragastric administration of iossorbide mononnirata aqueous solution at the dosage of 3.125 mg·kg~(-1)·d~(-1),the low-,middle-and high-dose Chinese medicine groups were given intragastric administration of Stasisdosage of 10.4, 20.8, 41.6 g · kg~(-1)· d~(-1), respectively, and the blank group and model group were given intragastric administration of the same volume of normal saline. After preventive medication for 7 days,rats except for the blank group were given intraperitoneal injection of isoprenaline to establish acute myocardial ischemia model. And then ST-segment deviation in ECG was measured,hematoxylin-eosin(HE)staining method was used to observe the structure of rat myocardial tissues,enzyme-linked immunosorbent assay(ELISA)was used to detect the serum content of endothelin 1(ET-1),qPCR method was used to determine the mRNA expression levels of RhoA and ROCK1 in rat myocardial tissues. Results Compared with the blank group,the large myocardial fibers were ruptured,bleeding was seen in the mesenchyme,and total ST-segment deviation,the serum content of ET-1,and the mRNA expression levels of RhoA and ROCK1 were increased in the model group(P<0.05). Compared with the model group,the myocardial fiber damage was improved,bleeding was less in the mesenchyme,and total ST-segment deviation,the serum content of ET-1,and the mRNA expression levels of RhoA and ROCK1 were decreased in the various medication groups(P<0.05). Conclusion Stasis-resolving and Phlegm-expelling Recipe has effects on improving the myocardial ischemia,and the mechanism may be related with the decrease of the mRNA expression levels of RhoA and ROCK1, which contributes to inhibiting myocardial contraction and increasing myocardial blood flow.
Objective To observe the effect of Stasis-resolving and Phlegm-expelling Recipe on the mRNA expression of RhoA and Rho-associated coiled-coil forming protein kinase 1(ROCK1)in myocardial tissues of acute myocardial ischemia rats,to explore its preventive mechanism. Methods Sixty SD rats were divided into blank group, model group, western medicine group, and lowgroups, 10 rats in each group. The western medicine group was given intragastric administration of iossorbide mononnirata aqueous solution at the dosage of 3.125 mg·kg~(-1)·d~(-1),the low-,middle-and high-dose Chinese medicine groups were given intragastric administration of Stasisdosage of 10.4, 20.8, 41.6 g · kg~(-1)· d~(-1), respectively, and the blank group and model group were given intragastric administration of the same volume of normal saline. After preventive medication for 7 days,rats except for the blank group were given intraperitoneal injection of isoprenaline to establish acute myocardial ischemia model. And then ST-segment deviation in ECG was measured,hematoxylin-eosin(HE)staining method was used to observe the structure of rat myocardial tissues,enzyme-linked immunosorbent assay(ELISA)was used to detect the serum content of endothelin 1(ET-1),qPCR method was used to determine the mRNA expression levels of RhoA and ROCK1 in rat myocardial tissues. Results Compared with the blank group,the large myocardial fibers were ruptured,bleeding was seen in the mesenchyme,and total ST-segment deviation,the serum content of ET-1,and the mRNA expression levels of RhoA and ROCK1 were increased in the model group(P<0.05). Compared with the model group,the myocardial fiber damage was improved,bleeding was less in the mesenchyme,and total ST-segment deviation,the serum content of ET-1,and the mRNA expression levels of RhoA and ROCK1 were decreased in the various medication groups(P<0.05). Conclusion Stasis-resolving and Phlegm-expelling Recipe has effects on improving the myocardial ischemia,and the mechanism may be related with the decrease of the mRNA expression levels of RhoA and ROCK1, which contributes to inhibiting myocardial contraction and increasing myocardial blood flow.
引文
[1]国家卫生计生委合理用药专家委员会,中国药师协会.冠心病合理用药指南(第2版)[J].中国医学前沿杂志(电子版),2018,10(6):1.
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[7]邵晓姣,侯国亮,梁繁荣,等.针刺对急性心肌缺血大鼠心肌组织氯离子通道调控蛋白CFTR、ClC-2表达的影响[J].北京中医药大学学报,2014,37(4):285.
[8]杨祎.血脉病理论体系构建[D].沈阳:辽宁中医药大学,2016.
[9]张云帆.丹红注射液治疗急性心肌缺血患者的临床疗效[J].中国药物经济学,2016,11(1):59.
[10]张东,贾连群,杨关林,等.化瘀祛痰方对异丙肾上腺素(ISO)急性心肌缺血大鼠心肌细胞结构、心电图ST段总偏移值、MDA、SOD、LDH、CK表达影响随机平行对照研究[J].实用中医内科杂志,2018,32(6):69.
[11]袁娅妮,毛福英,刘俊梅,等.甜菜碱调控RhoA/ROCK信号通路抑制大鼠急性心肌缺血损伤[J].中成药,2015,37(3):492.
[12]皇甫海全.基于RhoA/ROCK1信号通路探讨养心汤对大鼠血管内皮损伤的影响[D].哈尔滨:黑龙江中医药大学,2018.
[13]王亚光,王鹏,刘洪光,等.羟基红花黄色素通过RhoA/ROCK通路保护大鼠心肌再灌注损伤的机制研究[J].临床心血管病杂志,2015,31(7):791.
[14]郭振龙.苦参碱调控RhoA/ROCK信号通路抑制异丙肾上腺素致大鼠心肌肥厚作用及分子机制研究[D].银川:宁夏医科大学,2015.
[15]雷尚芳,鲍升娟,郭俐宏,等.红景天胶囊对兔急性心肌缺血再灌注损伤的保护作用[J].长春中医药大学学报,2015,31(4):673.
[16]焦轶.映山红花总黄酮抗心肌缺血损伤作用的H2S介导ROCK通路抑制机制[D].合肥:安徽医科大学,2015.
[2]王永刚,李彩红,于远望,等.双参通冠方对心肌梗死模型大鼠VEGF表达和炎性因子的影响[J].长春中医药大学学报,2017,33(3):348.
[3]刘福青.党参合剂对急性心肌缺血大鼠血液流变学的影响[J].中成药,2013,35(6):1152.
[4]宋亚娟,王欣,张丹丹,等.冠通活瘀胶囊对大鼠急性心肌缺血的保护作用[J].中国临床药理学与治疗学,2011,16(1):42.
[5]陈韦.化瘀祛痰颗粒对大鼠急性心肌缺血心肌微循环的保护作用[D].沈阳:辽宁中医药大学,2007.
[6]杨勇,容蓉,陈明强,等.异丙肾上腺素诱导小鼠急性心肌缺血模型的方法比较[J].中药药理与临床,2010,26(5):153.
[7]邵晓姣,侯国亮,梁繁荣,等.针刺对急性心肌缺血大鼠心肌组织氯离子通道调控蛋白CFTR、ClC-2表达的影响[J].北京中医药大学学报,2014,37(4):285.
[8]杨祎.血脉病理论体系构建[D].沈阳:辽宁中医药大学,2016.
[9]张云帆.丹红注射液治疗急性心肌缺血患者的临床疗效[J].中国药物经济学,2016,11(1):59.
[10]张东,贾连群,杨关林,等.化瘀祛痰方对异丙肾上腺素(ISO)急性心肌缺血大鼠心肌细胞结构、心电图ST段总偏移值、MDA、SOD、LDH、CK表达影响随机平行对照研究[J].实用中医内科杂志,2018,32(6):69.
[11]袁娅妮,毛福英,刘俊梅,等.甜菜碱调控RhoA/ROCK信号通路抑制大鼠急性心肌缺血损伤[J].中成药,2015,37(3):492.
[12]皇甫海全.基于RhoA/ROCK1信号通路探讨养心汤对大鼠血管内皮损伤的影响[D].哈尔滨:黑龙江中医药大学,2018.
[13]王亚光,王鹏,刘洪光,等.羟基红花黄色素通过RhoA/ROCK通路保护大鼠心肌再灌注损伤的机制研究[J].临床心血管病杂志,2015,31(7):791.
[14]郭振龙.苦参碱调控RhoA/ROCK信号通路抑制异丙肾上腺素致大鼠心肌肥厚作用及分子机制研究[D].银川:宁夏医科大学,2015.
[15]雷尚芳,鲍升娟,郭俐宏,等.红景天胶囊对兔急性心肌缺血再灌注损伤的保护作用[J].长春中医药大学学报,2015,31(4):673.
[16]焦轶.映山红花总黄酮抗心肌缺血损伤作用的H2S介导ROCK通路抑制机制[D].合肥:安徽医科大学,2015.
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