Beneficial effects of trimetazidine on expression of serotonin and serotonin transporter in rats with myocardial infarction and depression

Figures & data

Table 1 Time points of all treatments for all groups

Data	Sham	MI	Depression	MI + depression
Receive treatment	6th–33rd	6th–33rd	5th–32nd	1st–28th
Pathological procedures	34th	34th	33rd–34th	29th–34th
Sacrifice 3 days thereafter	37th	37th	37th	37th

Abbreviation: MI, myocardial infarction.

Table 2 Multivariate linear regression analysis of serum 5-HT of different models and pretreatments

Serum 5-HT	Unstandardized coefficients		Standardized coefficients	t	P-value
	B	Std error	Beta
Constant	363.23	8.67		41.91	<0.01
x1	−187.08	12.26	−1.07	−15.26	<0.01
x2	−168.54	12.26	−0.87	−13.75	<0.01
x3	−180.72	12.85	−0.90	−14.06	<0.01
x4	−87.96	11.46	−0.54	−7.67	<0.01
x1*x4	133.26	15.73	0.66	8.47	<0.01
x2*x4	288.03	16.78	1.12	17.16	<0.01
x3*x4	253.50	17.22	0.98	14.72	<0.01

Notes: Constant: sham pretreated with saline; y: value of serum 5-HT; x₁: MI pretreated with saline; x₂: depression pretreated with saline; x₃: MI + depression pretreated with saline; x₄: pretreated with trimetazidine; x₁*x₄: the interaction of MI and trimetazidine; x₂*x₄: the interaction of depression and trimetazidine; x₃*x₄: the interaction of MI + depression and trimetazidine.

Abbreviations: MI, myocardial infarction; 5-HT, 5-hydroxytryptamine.

Table 3 Multivariate linear regression analysis of serum SERT of different models and pretreatments

Serum SERT	Unstandardized coefficients		Standardized coefficients	t	Sig
	B	Std error	Beta
Constant	214.81	10.26		20.946	0.000
x1	6.19	13.89	0.045	0.446	0.658
x2	27.41	13.89	0.191	1.974	0.055
x3	59.99	13.89	0.418	4.320	0.000
x4	−94.40	13.07	−0.771	−7.221	0.000
x1*x4	130.30	18.01	0.778	7.236	0.000
x2*x4	155.27	18.61	0.821	8.345	0.000
x3*x4	108.08	18.61	0.571	5.809	0.000

Notes: Constant: sham pretreated with saline; y: value of serum SERT; x₁: MI pretreated with saline; x₂: depression pretreated with saline; x₃: MI + depression pretreated with saline; x₄: pretreated with trimetazidine; x₁*x₄: the interaction of MI and trimetazidine; x₂*x₄: the interaction of depression and trimetazidine; x₃*x₄: the interaction of MI + depression and trimetazidine.

Abbreviations: MI, myocardial infarction; SERT, serotonin transporter.

Table 4 Multivariate linear regression analysis of platelet 5-HT of different models and pretreatments

Platelet 5-HT	Unstandardized coefficients		Standardized coefficients	t	Sig
	B	Std error	Beta
Constant	200.27	7.07		28.329	0.000
x1	−70.53	10.49	−0.489	−6.726	0.000
x2	−25.12	10.00	−0.162	−2.512	0.016
x3	−19.43	10.49	−0.121	−1.853	0.071
x4	121.19	9.35	0.916	12.959	0.000
x1*x4	53.92	13.32	0.325	4.049	0.000
x2*x4	−44.73	13.69	−0.219	−3.267	0.002
x3*x4	−60.98	14.05	−0.298	−4.341	0.000

Notes: Constant: sham pretreated with saline; y: value of platelet 5-HT; x₁: MI pretreated with saline; x₂: depression pretreated with saline; x₃: MI + depression pretreated with saline; x₄: pretreated with trimetazidine; x₁*x₄: the interaction of MI and trimetazidine; x₂*x₄: the interaction of depression and trimetazidine; x₃*x₄: the interaction of MI + depression and trimetazidine.

Abbreviations: MI, myocardial infarction; 5-HT, 5-hydroxytryptamine.

Table 5 Multivariate linear regression analysis of platelet SERT of different models and pretreatments

Platelet SERT	Unstandardized coefficients		Standardized coefficients	t	Sig
	B	Std error	Beta
Constant	274.03	8.64		31.724	0.000
x1	48.82	12.22	0.355	3.996	0.000
x2	4.18	12.22	0.029	0.342	0.734
x3	7.80	12.22	0.054	0.638	0.527
x4	−120.89	11.43	−0.989	−10.580	0.000
x1*x4	45.93	16.16	0.272	2.842	0.007
x2*x4	30.77	16.73	0.161	1.840	0.073
x3*x4	8.80	16.73	0.046	0.526	0.602

Notes: Constant: sham pretreated with saline; y: value of platelet SERT; x₁: MI pretreated with saline; x₂: depression pretreated with saline; x₃: MI + depression pretreated with saline; x₄: pretreated with trimetazidine; x₁*x₄: the interaction of MI and trimetazidine; x₂*x₄: the interaction of depression and trimetazidine; x₃*x₄: the interaction of MI + depression and trimetazidine.

Abbreviations: MI, myocardial infarction; SERT, serotonin transporter.

Figure 1 (A) In the saline group, the MI, depression, and MI + depression subgroups exhibited levels of serum 5-HT significantly lower than sham-operated rat levels. In the trimetazidine group, depression and MI + depression subgroups had significantly higher serum 5-HT levels than in the sham-operated counterparts. The treatment significantly decreased serum 5-HT for sham operation rats, and significantly increased serum 5-HT for MI, depression, and MI + depression rats compared with the saline group. *P<0.05, indicating a statistically significant difference between the control and trimetazidine group. (B) In the saline group, the MI, depression, and MI + depression rats had significantly lower platelet 5-HT levels compared to sham-operated rats. In the trimetazidine group, depression and MI + depression rats had significantly lower platelet 5-HT levels than sham-operated rats. The treatment significantly increased platelet 5-HT for all disease models compared to the saline group. *P<0.05, indicating a statistically significant difference between the control and trimetazidine group.

Abbreviations: MI, myocardial infarction; 5-HT, 5-hydroxytryptamine.

Figure 2 (A) In the saline group, MI, depression, and MI + depression rats had higher serum SERT than sham-operated rats but it was not significantly different. In the trimetazidine group, serum levels of SERT were significantly higher than sham-operated rats in the MI, depression, and MI + depression rats. The treatment significantly decreased serum SERT in sham-operated rats, and significantly increased serum SERT in depression rats compared to the control. *P<0.05, indicating a statistically significant difference between the control and trimetazidine group. (B) In the saline group, MI, depression, and MI + depression subgroups had increased platelet SERT levels compared to sham-operated rats but it was not significant. In the trimetazidine group, MI, MI + depression, and depression rats had significant increases in platelet SERT over sham-operated rats. The treatment caused significant decreases in platelet SERT in all disease models compared to the control. *P<0.05, indicating a statistically significant difference between the control and trimetazidine group.

Abbreviations: MI, myocardial infarction; SERT, serotonin transporter.

Table 6 Posttreatment 5-HT, SERT levels in MI rats

Indicators	Saline group (pg/mL)	Trimetazidine group (pg/mL)	P-value
Serum 5-HT	215.66±4.96	292.22±29.44	0.001
Platelet 5-HT	491.52±28.71	270.68±25.87	0.000
Serum SERT	170.56±33.40	220.72±28.25	0.024
Platelet SERT	151.22±31.73	123.88±8.67	0.090

Abbreviations: MI, myocardial infarction; SERT, serotonin transporter; 5-HT, 5-hydroxytryptamine.