Effect of remimazolam on myocardial injury in rats with acute myocardial infarction by regulating the EPAC1/RAP1 signaling pathway

doi:10.11958/20230890

Abstract

Abstract:

Objective To investigate the effect of remimazolam on myocardial injury in rats with acute myocardial infarction (AMI) by regulating exchange proteins directly activated by cAMP (EPAC1)/RAS-related protein 1 (RAP1) signaling pathway. Methods Rats were divided into the sham operation group, the model group, the remazolam group and the remazolam+8-CPT (EPAC1 agonist) group according to random number table method, with 20 rats in each group. Except for the sham operation group, AMI rat model was constructed by ligation of left anterior descending branch in the other groups. Ultrasonic apparatus for small animals was applied to detect cardiac function indicators. HE staining was applied to detect the pathological condition of myocardial tissue. Chemical colorimetry was applied to detect levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue of rats. JC-1 staining method was applied to detect the mitochondrial membrane potential of rat cardiomyocytes. TUNEL staining was used to detect the TUNEL positive rate of myocardial cells. Western blot assay was applied to detect expression levels of EPAC1, RAP1 and Caspase-3 proteins in myocardial tissue. Results Compared with the sham operation group, the myocardial tissue structure of rats in the model group was severely damaged and infiltrated with a large number of inflammatory cells. Cardiac function indicators left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), myocardial tissue MDA level, myocardial cell TUNEL positive rate, and myocardial tissue EPAC1, RAP1 and Caspase-3 protein expression levels were obviously increased, and the left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), myocardial tissue SOD level, cardiomyocytes mitochondrial membrane potential were obviously decreased (P<0.05). Compared with the model group, the myocardial tissue structure of rats in the ramazolam group was obviously restored, and inflammatory cell infiltration was reduced. The cardiac function indicators LVEDD, LVESD, myocardial tissue MDA level, myocardial cell TUNEL positive rate, and myocardial tissue EPAC1, RAP1 and Caspase-3 protein expression levels were obviously decreased, and LVEF, LVFS, myocardial tissue SOD level, cardiomyocytes mitochondrial membrane potential were obviously increased (P<0.05). Agonists of EPAC1 attenuated the mitigating effect of remazolam on myocardial injury in AMI rats. Conclusion Remimazolam may inhibit the EPAC1/RAP1 signaling pathway, inhibit myocardial cell apoptosis and alleviate myocardial injury in AMI rats.

Key words: myocardial infarction, myocardial damage, remimazolam, exchange proteins directly activated by cAMP, RAS-related

CLC Number:

R542.22

Figures/Tables 8

References 21

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组别	LVEDD/mm	LVESD/mm	LVEF	LVFS/%
假手术组	6.74±0.65	4.38±0.41	0.79±0.04	44.51±3.23
模型组	11.08±1.20^a	9.64±1.02^a	0.32±0.02^a	15.52±1.46^a
瑞马唑仑组	7.13±0.74^b	4.79±0.52^b	0.70±0.03^b	40.22±3.06^b
瑞马唑仑+ 8-CPT组	10.45±1.01^c	8.91±0.88^c	0.42±0.03^c	20.53±1.96^c
F	116.171^＊＊	264.461^＊＊	1 050.351^＊＊	635.773^＊＊

组别	LVEDD/mm	LVESD/mm	LVEF	LVFS/%
假手术组	6.74±0.65	4.38±0.41	0.79±0.04	44.51±3.23
模型组	11.08±1.20^a	9.64±1.02^a	0.32±0.02^a	15.52±1.46^a
瑞马唑仑组	7.13±0.74^b	4.79±0.52^b	0.70±0.03^b	40.22±3.06^b
瑞马唑仑+ 8-CPT组	10.45±1.01^c	8.91±0.88^c	0.42±0.03^c	20.53±1.96^c
F	116.171^＊＊	264.461^＊＊	1 050.351^＊＊	635.773^＊＊

组别	SOD/（U/mg）	MDA/（μmol/g）
假手术组	48.12±4.45	0.38±0.04
模型组	22.35±2.33^a	0.71±0.07^a
瑞马唑仑组	40.14±4.01^b	0.43±0.05^b
瑞马唑仑+8-CPT组	25.26±2.24^c	0.67±0.06^c
F	64.636^＊＊	44.061^＊＊

组别	SOD/（U/mg）	MDA/（μmol/g）
假手术组	48.12±4.45	0.38±0.04
模型组	22.35±2.33^a	0.71±0.07^a
瑞马唑仑组	40.14±4.01^b	0.43±0.05^b
瑞马唑仑+8-CPT组	25.26±2.24^c	0.67±0.06^c
F	64.636^＊＊	44.061^＊＊

组别	红绿荧光比值	TUNEL阳性率/%
假手术组	9.12±0.10	5.22±0.23
模型组	2.23±0.21^a	32.12±3.11^a
瑞马唑仑组	7.54±0.67^b	12.94±1.20^b
瑞马唑仑+8-CPT组	2.48±0.30^c	27.56±2.81^c
F	415.740^＊＊	164.791^＊＊