摘要
目的探讨富参颗粒对于阿霉素诱导心力衰竭大鼠心功能、心肌组织凋亡及内质网应激相关蛋白的影响，为研发新药物提供实验依据。方法50只大鼠分为阿霉素组40只，对照组10只，阿霉素组利用阿霉素造模，共8周，每周1次，每次剂量2mg／kg。采用超声心动仪检测，确认模型建立成功。模型建立后分别给予低剂量组（n=8）、中剂量组（n=8）、高剂量组（n=8）富参颗粒40、60、80mg／kg剂量。灌胃给药5周后，观察各组大鼠超声心动图变化，Westernbla印迹法检测各组大鼠B淋巴细胞瘤也基因（Bcl-2）、髓细胞白血病因子-1（Mcl-1）、Bcl-2同源蛋白X（Bax）、半胱氨酸天冬氨酸特异性蛋白酶-3（Caspase-3）、增强子结合蛋白同源蛋白（CHOP）、葡萄糖调节蛋白78（GRP78）蛋白表达变化，RT—PCR电泳方法检测各组大鼠Mcl-1、NOXAmRNA表达变化。结果经左室舒张末期内径（LVEDD）、左心室射血分数（LVEF）提示造模成功，富参颗粒中、高剂量组LVEDD、左室收缩末期内径（LVESD）、LVEF、左室短轴缩短率（Fs）均有改善。与模型组心脏组织相比，低剂量组、中剂量组和高剂量组心脏组织的Bcl-2、Mcl-1蛋白表达水平明显升高，NOXA、Bax蛋白表达水平降低，差异有统计学意义（P〈0．05）。与模型组心脏组织相比，低、中、高剂量组心脏组织的CHOP、GRP78蛋白表达水平明显降低，差异有统计学意义（P〈0．05）。与模型组心脏组织相比，低、中、高剂量组心脏组织的Mcl-1mR—NA表达水平显著升高，NOXAmRNA表达水平显著降低（P〈0．05）。结论明确富参颗粒抑制了过度的内质网应激，从而降低了心肌细胞凋亡，最终达到治疗心衰的目的。
Objective To explore the contribution of endoplasmic reticulum stress to cardiac myo- eyte apoptosis in mouse congestive heart failure induced by Doxorubicin. Methods Doxorubicin （DOX） was administered intraperitoneally to rats, 2 mg/kg doses over 8 weeks. Echocardiographic and hemodynam- ics measurements were obtained at 8 weeks after treatment. Then left ventricular （L） samples were col- lected. The successfully established rats were divided into 3 groups （ Fu Shen Ke Li 40 mg/kg, 60 mg/kg, and 80 mg/kg）. After 5 weeks post the operation, an echocardiographic was performed on all the rats under uarcotism, Western blot to test the B-cell lymphoma-2 （Be1-2） , myeloid cell leukemia-1 （ Mcl-1 ） , Bcl-2- Associated X （ Bax）, Caspase-3, C/EBP homologous protein （ CHOP）, and 78-kDa glucose-regulated pro- tein （GRP78） , and reverse transcription-polymerase chain reaction （RT-PCR） to test the mRNA expres- sion levels of Mcl-1, and NOXA. Results The left ventricular end-diastolic diameter （LVEDD） , left ven- trieular end systolic diameter （LVESD） , left ventricular ejection fraction （LVEF） prompted modeling suc- cess The left ventricular end-diastolic diameter （LVEDD）, left ventricular ejection fraction （LVEF） , and fractional shortening （FS） have been improved in high and middle groups of Fu Shen Ke Li. Compared to the model group, higher expression levels of Bcl-2, and Mcl-1 were, lower expressions of Bax, NOXA, CHOP, and GRP78 were （P 〈0. 05） in 3 groups of Fu Shen Ke Li. Compared to the model group, there were higher mRNA expression level of Mcl-1 was , lower mRNA expression of NOXA was （P 〈 0. 05） in 3groups of Fu Shen Ke Li. Conclusions Fu Shen Ke Li depresses endoplasmic reticulum stress, which can reduce the apoptosis of myocardial cells, and ultimately achieve the purpose of treatment of heart failure.
出处
《中国医师杂志》
CAS
2017年第4期556-559,共4页
Journal of Chinese Physician
