Mechanism of Salvia Miltiorrhiza on the Improvement of Myocardial Function in Patients with Dilated Cardiomyopathy†

doi:10.7503/cjcu20150984

Abstract

Abstract:

Metabonomics combined with molecular biology were used to investigate the mechanisms of anti-dilated cardiomyopathy treated by depside salt from Salvia miltiorrhiza. The serum metabolic profiling of control group, model group and treatment group were analysed by principle component analysis(PCA). The potential biomarkers were selected with the help of orthogonal partial least squares discriminant analysis(OPLS-DA). As results, nine potential biomarkers including the PS[16∶0/18∶1(9Z)], LysoPC(16∶0), LysoPC[20∶4(5Z, 8Z, 11Z, 14Z)], LysoPC[22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], cholesterol sulfate, taurohyocholate, γ-linolenic acid, docosapentaenoic acid and 9'-carboxy-γ-chromanol were identified respectively. In addition, the relative content of γ-linolenic acid, docosapentaenoic acid and 9'-carboxy-γ-chromanol decreased in the model group, while increased in the treatment group. With the help of western bloting and enzyme-linked immunosorbent method, we confirmed that the depside salt from Salvia miltiorrhiza influenced the expression levels of superoxide disproportionation(SOD), malondialdehyde(MDA), Bcl-2 and Bax protein molecule(the proteins mentioned above were related with γ-linolenic acid and 9'-carboxyl-γ-tocopherol), and then reduced the amount of the apoptosis myocardial cell induced by oxidative stress, and treated the the dilated cardiomyopathy caused by adriamycin finally.

Key words: Dilated cardiomyopathy, Salvia miltiorrhiza, Metabonomics, Mass spectrometry, Oxidative stress

CLC Number:

O657

TrendMD:

WANG Xiye, SHAN Xiaotong, WANG Yilin, LI Dan, ZHAO Ming, XU Liang. Mechanism of Salvia Miltiorrhiza on the Improvement of Myocardial Function in Patients with Dilated Cardiomyopathy^†[J]. Chem. J. Chinese Universities, 2016, 37(5): 844.

Figures/Tables 9

Fig.1 Heart color doppler ultrasound of control group(A), model group(B) and treatment group(C)

Table 1 Effect of salvianolate miltiorrhiza on ventricular structure and ejection fraction in rats with dilated cardiomyopathy

Group	LVIDd/mm	LVSd/mm	LVPWDd/mm	LVEF(%)
C	4.73±0.41^**	1.74±0.1^**	2.1±0.33^**	85.5±3.23^**
M	5.83±0.59	2.08±0.19	1.73±0.07	70.4±5.69
T	5.26±0.33^**	1.99±0.18^**	1.91±0.09^**	76.2±3.19^**

Fig.2 Base peak intensity chromatograms(BPI) under the ESI+ mode(A, C, E) and ESI- mode(B, D, F) (A), (B) Control group; (C), (D) model group; (E), (F) treatment group.

Fig.3 PCA score plots obtained from the metabolic profiles of the control group, model group and treatment group under positive(A) and negative ion modes(B)

Fig.4 OPLS-DA score plots(A, C) and S-plots(B, D) obtained from the metabolic profiles of the control group and model group under positive(A, B) and negative ion modes(C, D)

Table 2 Potential biomarkers between control group and model group

t_R/min	Measured mass	10⁶Mass deviation	MS², m/z	Chemical formula	Compound	ESI mode
6.89	762.5300	2.6	745.5, 265.3, 239.2, 88.0	C₄₀H₇₆NO₁₀P	PS[16∶0/18∶1(9Z)]	+
4.56	496.3406	1.6	330.1	C₂₄H₅₀NO₇P	LysoPC(16∶0)	+
4.44	544.3402	0.7	378.2	C₂₈H₅₀NO₇P	LysoPC[20∶4	+
					(5Z,8Z,11Z,14Z)]
4.45	568.3394	0.7	402.7	C₃₀H₅₀NO₇P	LysoPC[22∶6	+
					(4Z,7Z,10Z,13Z,16Z,19Z)]
5.97	465.3038	1.3	97.1	C₂₇H₄₆O₄S	Cholesterol sulfate	-
3.66	514.2833	2.1	498.5, 480.6, 462.6	C₂₆H₄₅NO₇S	Taurohyocholate	-
4.28	277.2167	2.2	93.2, 79.4, 67.3, 55.6	C₁₈H₃₀O₂	Gamma-Linolenic acid	-
4.64	329.2481	1.5	271.2	C₂₂H₃₄O₂	Docosapentaenoic acid	-
4.96	375.2533	2.1	344.2, 288.6, 275.3, 101.5	C₂₃H₃₆O₄	9'-Carboxy-γ-chromanol	-

Fig.5 Heatmap of metabolites between control(C) group, model(M) group and treatment(T) groupa. γ-linolenic acid; b. docosapentaenoic acid; c. 9'-carboxy-γ-chromanol.

Fig.6 Expression levels of MDA(A) and SOD(B) protein of rats left ventricular myocardial tissue in control group, model group and treatment group*P<0.05, **P<0.01(vs. model group).

Fig.7 Western blot analysis(A) and expression levels(B) of Bcl-2 and Bax protein of rats left ventricular myocardial tissue in control group, model group and treatment group**P<0.01(vs. model group).

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