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Effect of Shuangshen Ningxin Capsules on Cardiac Function and Hemodynamics in Rats with Coronary Microvascular Dysfunction / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 41-50, 2021.
Article in Chinese | WPRIM | ID: wpr-905925
ABSTRACT

Objective:

To investigate the effect of Shuangshen Ningxin capsules (SSNX) on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction.

Method:

Rats were randomly divided into a sham operation group, a model group, a nicorandil group (5 mg·kg<sup>-1</sup>), and high- (180 mg·kg<sup>-1</sup>), medium- (90 mg·kg<sup>-1</sup>), and low-dose (45 mg·kg<sup>-1</sup>) SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration, the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres (40-120 μm, about 1 000 microspheres). Twenty-four hours after modeling, left ventricular internal dimension in diastole (LVIDd), left ventricular internal dimension in systole (LVIDs) left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV), cardiac output (CO), left ventricular ejection fraction (EF), and left ventricular shortening rate (FS) were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase in left ventricular pressure (LV+dp/dt<sub>max</sub>), and maximum rate of decrease in left ventricular pressure (LV-dp/dt<sub>max</sub>), and the mean arterial pressure (MAP) was calculated. Heart rate (HR) was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Enzyme-linked immunosorbent assayELISA) was used to detect serum cardiac troponin T (cTnT). Western blot was used to detect the protein expression of Caspase-3, Bcl-2, and Bax, and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the area of myocardial infarction. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of the myocardium.

Result:

As revealed by echocardiography, compared with the sham operation group, the model group showed reduced SV, CO, EF, and FS (<italic>P</italic><0.01), and increased LVIDs and LVEDV (<italic>P</italic><0.01). Compared with the model group, the SSNX groups showed increased EF (<italic>P</italic><0.05, <italic>P</italic><0.01) and FS (<italic>P</italic><0.01), and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV, and increased LVEDV, SV, and CO (<italic>P</italic><0.05, <italic>P</italic><0.01). SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, and LV-dp/dt<sub>max</sub> in the model group were lower than those in the sham operation group (<italic>P</italic><0.01), while there was no significant difference in HR. SSNX improved hemodynamics of rats, and increased SBP, DBP, MAP, LVSP, LV+dp/dt<sub>max</sub>, LV-dp/dt<sub>max</sub>, and HR as compared with the model group (<italic>P</italic><0.05, <italic>P</italic><0.01). The serum CK, LDH, CK-MB, and cTnT levels in the model group were higher than those in the sham operation group (<italic>P</italic><0.01). Compared with the model group, SSNX groups reduced serum CK, LDH, CK-MB, and cTnT (<italic>P</italic><0.05,<italic> P</italic><0.01). Compared with the sham operation group, the model group displayed increased expression of Caspase-3 protein in the myocardium (<italic>P</italic><0.01) and reduced expression of Bcl-2 protein (<italic>P</italic><0.05). The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group, and statistical difference was observed between the low-dose SSNX group and the model group (<italic>P</italic><0.05). Compared with the model group, the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium, and the statistical difference was observed in the high-dose SSNX group <italic>(P</italic><0.01). As demonstrated by the TTC staining, compared with the model group, SSNX groups showed reduced areas of myocardial infarction (<italic>P</italic><0.01). The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group.

Conclusion:

SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres, improve cardiac hemodynamics, reduce the area of myocardial infarction, and decrease CK, LDH, CK-MB, and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article