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中药播娘蒿的寡糖成分通过改善心力衰竭大鼠的心功能和水液代谢发挥抗心力衰竭作用。

Oligosaccharides composition of Descurainiae sophia exerts anti-heart failure by improving heart function and water-liquid metabolism in rats with heart failure.

机构信息

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China.

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China.

出版信息

Biomed Pharmacother. 2020 Sep;129:110487. doi: 10.1016/j.biopha.2020.110487. Epub 2020 Jul 3.

Abstract

PURPOSE

To investigate the protective effect of Oligosaccharides composition of Descurainiae sophia on doxorubicin-induced heart failure in rats, and to study its mechanism.

METHOD

A rat model of heart failure was established in 180-220 g male Sprague-Dawley rats by low-dose intraperitoneal injection of doxorubicin for 6 weeks. Four weeks after continuous administration, echocardiography was used to detect left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) in each group, and left ventricular short axis shortening rate (LVFS) and ejection fraction (LVEF) were calculated. ELISA method was used to detecte the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), troponin I (cTnI), creatine kinase (CK), angiotensin II (Ang II), aldosterone (ALD), arginine pressurization AVP, Renin, Endothelin (ET-1), Nitric Oxide (NO), AQP2 in urine. 6 h cumulative urine output was measured by metabolic cage method after administration for 3 weeks. The urine osmotic pressure was measured by freezing point method. The expression of AQP2 protein in kidney was detected by Western blot method. The changes of myocardial morphology were observed.

RESULTS

Compared with the normal control group, the heart rate of the model group was significantly increased (P < 0.01). LVESD and LVEDD were significantly increased (P < 0.01), LVEF and LVFS were significantly decreased (P < 0.01). The levels of CK, cTnI, NO, ET-1, BNP, ANP, ALD, AngII, Renin, AQP2, AVP and osmotic pressure were significantly increased (P < 0.01). Urine output was significantly decreased (P < 0.01). The heart HE showed obvious lesions. Compared with the model group, the Oligosaccharides composition of Descurainiae sophia significantly reduced the heart rate (P < 0.05), decreased LVESD and LVEDD (P < 0.01 or P < 0.05), and increased LVFS and LVEF values (P < 0.01). Oligosaccharides composition of Descurainiae sophia could significantly improve pathological damage of the heart, decrease the levels of cTnI, BNP, AngII, ALD, Renin, AVP in the serum, osmotic pressure and AQP2in the urine (P < 0.01 or P < 0.05), down-regulate the expression of AQP2 protein in the renal(P < 0.01), increase urine volume (P < 0.05).

CONCLUSION

Oligosaccharides composition of Descurainiae sophia can significantly improve cardiac function and the disorder of water metabolism in rats with heart failure. Oligosaccharides composition of Descurainiae sophia exerts anti- heart failure through the RAAS system and the arginine vasopressin system.

摘要

目的

研究中药葶苈子总苷对阿霉素诱导的心力衰竭大鼠的保护作用,并探讨其作用机制。

方法

采用小剂量阿霉素腹腔注射 6 周建立大鼠心力衰竭模型。连续给药 4 周后,应用超声心动图检测各组大鼠左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD),计算左室短轴缩短率(LVFS)和左室射血分数(LVEF)。酶联免疫吸附法检测各组大鼠血清中心房利钠肽(ANP)、脑利钠肽(BNP)、肌钙蛋白 I(cTnI)、肌酸激酶同工酶(CK)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、血管加压素(AVP)、肾素、内皮素(ET-1)、一氧化氮(NO)、水通道蛋白 2(AQP2)的水平。给药 3 周后,采用代谢笼法测量 6 h 累积尿量,采用冰点法测量尿渗透压。采用 Western blot 法检测肾脏 AQP2 蛋白的表达变化。观察心肌形态学变化。

结果

与正常对照组比较,模型组大鼠心率明显升高(P<0.01)。LVESD 和 LVEDD 明显增加(P<0.01),LVEF 和 LVFS 明显降低(P<0.01)。CK、cTnI、NO、ET-1、BNP、ANP、ALD、AngⅡ、肾素、AVP、渗透压、AQP2 水平均明显升高(P<0.01)。尿量明显减少(P<0.01)。心脏 HE 显示明显病变。与模型组比较,葶苈子总苷可显著降低心率(P<0.05),降低 LVESD 和 LVEDD(P<0.01 或 P<0.05),升高 LVFS 和 LVEF 值(P<0.01)。葶苈子总苷可明显改善心脏的病理损伤,降低血清中 cTnI、BNP、AngⅡ、ALD、肾素、AVP、渗透压和尿 AQP2 水平(P<0.01 或 P<0.05),下调肾脏 AQP2 蛋白表达(P<0.01),增加尿量(P<0.05)。

结论

葶苈子总苷可显著改善心力衰竭大鼠心功能和水代谢紊乱,其抗心力衰竭作用可能与 RASS 系统和精氨酸加压素系统有关。

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