补肾活血复方介导钙转运蛋白肌浆网上的心肌钙转运蛋白、受磷蛋白调节内质网应激缓解慢性心衰大鼠心肌损伤  

Bushen Huoxue compound mediates SERCA2a and PLB proteins to regulate endoplasmic reticulum stress and alleviate myocardial injury in rats with chronic heart failure

作　　者：邹文聪 张艳[2] 许瑞 尹文浩 刘贤娴 申欣宜 ZOU Wencong;ZHANG Yan;XU Rui;YIN Wenhao;LIU Xianxian;SHEN Xinyi(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,沈阳110847 [2]辽宁中医药大学附属医院专家科 [3]辽宁中医药大学附属第二医院心内科

出　　处：《环球中医药》2023年第5期817-823,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81774157、82174241)。

摘　　要：目的观察补肾活血复方对慢性心力衰竭(chronic heart failure,CHF)大鼠钙转运蛋白肌浆网上的心肌钙转运蛋白(sarcoplasmic reticulum Ca 2+-ATPase2a,SERCA2a)、受磷蛋白(phospholamban,PLB)的影响,进一步探讨内质网应激与心肌损伤、心衰的相互关系。方法将雄性SPF级SD大鼠60只,随机选取15只为分成空白组,其余45只进行冠脉结扎后力竭式游泳构建CHF造型,再随机分配为心衰组、补肾活血复方组、卡托普利组。空白组与补肾活血复方组,分别应用等剂量的生理盐水与补肾活血复方(9.2 g/kg)灌胃,卡托普利组运用卡托普利(12.5 mg/kg)灌胃,各组干预4周后,运用动物心脏超声仪器记录心率、射血分数、收缩—舒张心室内径等。各组N段脑钠肽前体含量,苏木精—伊红染色观察大鼠心肌损伤情况,同时检测:SERCA2a、PLB。结果与空白组相比,模型组的SERCA2a含量明显降低。与模型组相比,空白组、补肾活血复方组、卡托普利组表达明显升高(P<0.01)。补肾活血复方组、卡托普利组两组相比差异无统计学意义。与空白组相比,模型组的SERCA2a含量明显升高;与模型组相比,空白组、补肾活血复方组、卡托普利组表达明显降低,补肾活血复方组、卡托普利组相比差异无统计学意义。结论补肾活血复方可以有效阻止心肌内质网应激反应,协调心肌细胞中Ca 2+平衡稳态,恢复CHF大鼠显著抑制CHF大鼠心肌组织中的内质网应激反应。补肾活血复方汤对心力衰竭大鼠心功能的改善可能来源于对SERCA2a、PLB蛋白的调控作用。Objective The influence of kidney tonifying and blood circulation compound on ER calcium ion ATP enzyme(SERCA2a)and phosphoprotein(PLB)in rats with chronic heart failure was observed,and the relationship among ER stress and myocardial injury and heart failure was further explored.Methods 60 male SPF SD rats were randomly divided into blank group,the other 45 ratshad exhausted swimming after coronary ligation to build a chronic heart failure model,then randomly assigned to heart failure group,Bushen Huoxue group,and captopril group,the blank group and Bushen Huoxue group were applied with equal doses of normal saline and tonifying kidney and promoting blood circulation and compound gastric lavage,respectively,the rats in the western medicine group using captopril for gavage,after 4 weeks of the intervention in each group,the levels of heart rate,ejection fraction,contraction-diastolic ventricular diameter were recorded.For BNP content of each group,rat myocardial injury was observed by HE staining,reactive oxygen species(ROS)was detected by immunofluorescence,and ER calcium ion ATP enzyme:SERCA2a,phosphoprotein:PLB.Results The SERCA2a content was significantly decreased in the model group compared with the blank group.The increasing expression was observed in the Sham,Bushen Huoxue,and captopril groups when compared with the model group(P<0.05).The level of PLB in Bushen Huoxue and captopril group were increased in the model group compared with the blank group.The expression in the Sham,Bushen Huoxue,and captopril group were decreased significantly compared with the model group.Conclusion There is no significant difference between the Bushen Huoxue group and the captopril group,which shows that the compound can effectively prevent myocardial ER stress response,coordinate Ca 2+balance homeostasis in cardiomyocytes,and restore CHF rats to significantly inhibit ER stress response in myocardial tissue of CHF rats.The improvement of heart function may come from the regulation of SERCA2a and PLB proteins.

关 键 词：补肾活血复方 慢性心力衰竭 内质网应激 钙转运蛋白肌浆网上的心肌钙转运蛋白 受磷蛋白 

分 类 号：R285.5[医药卫生—中药学]