Study on the Intervention Effects of Pinggan Prescription(平肝方) on Spontaneously Hypertensive Rats Based on Metabonomic and Pharmacodynamic Methods
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摘要
Objective: To investigate the effects of Pinggan Prescription(平肝方, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic. Methods: A total of 32 male spontaneously hypertensive rats(SHRs) were randomly divided into two groups by using the random number table method:a treatment group(n=18) and a model group(n=14). The Wistar rats(n=14) were used as the normal group.Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg(PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate(c AMP) and angiotensinⅡ(Ang Ⅱ) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry(GC-MS). Results: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP(P<0.01). The pharmacodynamic results illustrated that the content of Ang Ⅱincreased with the raised blood pressure and the c AMP expressed the converse trend. After curing with PGP, the content of Ang Ⅱ decreased, the difference between model group and treatment group was signi?cant(P<0.01),and the c AMP expressed the converse trend. Five potential biomarkers were identi?ed, including arachidonic acid,hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown signi?cantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were signi?cantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure. Conclusions: PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.
Objective: To investigate the effects of Pinggan Prescription(平肝方, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic. Methods: A total of 32 male spontaneously hypertensive rats(SHRs) were randomly divided into two groups by using the random number table method:a treatment group(n=18) and a model group(n=14). The Wistar rats(n=14) were used as the normal group.Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg(PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate(c AMP) and angiotensinⅡ(Ang Ⅱ) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry(GC-MS). Results: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP(P<0.01). The pharmacodynamic results illustrated that the content of Ang Ⅱincreased with the raised blood pressure and the c AMP expressed the converse trend. After curing with PGP, the content of Ang Ⅱ decreased, the difference between model group and treatment group was signi?cant(P<0.01),and the c AMP expressed the converse trend. Five potential biomarkers were identi?ed, including arachidonic acid,hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown signi?cantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were signi?cantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure. Conclusions: PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.
Objective: To investigate the effects of Pinggan Prescription(平肝方, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic. Methods: A total of 32 male spontaneously hypertensive rats(SHRs) were randomly divided into two groups by using the random number table method:a treatment group(n=18) and a model group(n=14). The Wistar rats(n=14) were used as the normal group.Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg(PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate(c AMP) and angiotensinⅡ(Ang Ⅱ) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry(GC-MS). Results: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP(P<0.01). The pharmacodynamic results illustrated that the content of Ang Ⅱincreased with the raised blood pressure and the c AMP expressed the converse trend. After curing with PGP, the content of Ang Ⅱ decreased, the difference between model group and treatment group was signi?cant(P<0.01),and the c AMP expressed the converse trend. Five potential biomarkers were identi?ed, including arachidonic acid,hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown signi?cantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were signi?cantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure. Conclusions: PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.
引文
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14.Li T,Bian CY.Cyclic adenosine monophosphate short-term treatment of chronic congestive heart failure,acute exacerbation of clinical observation.J Navy Med 2007;28:214-215.
15.L u o L F,W u W H,O u Y D S.T h e e u c o m m i a o f antihypertensive ingredients and step-down mechanism.Chin Tradit Herbal Drugs(Chin)2006;37:150-151.
16.Luo HL,He ZY,Feng B.Role of cAMP and cGMP in the regulation of b FGF gene expression of rat cardiomyocytes.Chin J Pathophysiol(Chin)2000;16:818-820.
17.Huang BX,Wang DW,Wang JF.Research advance in polyunsa-turated fatty acid.Agric Eng Tech 2009;8:26-30.
18.Sun SG,Wang YP.Research on blood pressure regulation of kidney.Chin J Evid Based Cardiovasc Med(Chin)2008;1:56-58.
19.Lu ZY,Zhong NS,eds.Internal medicine.Beijing:People's Health Publishing House;2008:252-253.
20.Wen Y,Wang HW,Lu HL,Hu XF,Shi H,Yang Y,et al.Fatty acid-induced insulin resistance in 3T3-L1 adiposities.Chin J Pathophysiol(Chin)2007;23:543-547.
21.Zhou LY,Cao MF,Wang H,Feng L,Ding H,Wei XB,et al.Protective effects of moderate ethanol consumption onβ-cell dysfunction induced by palmitate.J Shandong Univ Health Sci(Chin)2011;49:9-14.
22.Wu LL,ed.Cardiovascular pathophysiology.Beijing:Beijing Medical University Press;2005:63-64.
2.Wang GJ,Hao HP,A JY,Yan B,Zha WB.Prospective consideration on metabonomic approach to the study of holistic efficacies and involved mechanisms of traditional Chinese medicines.Chin J Natl Med(Chin)2009;7:82-89.
3.Nicholson JK,Lindon JC,Holmes E.Metabonomics:understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data.Xenobiotica1999;29:1181-1189.
4.Nicholson JK,Lindon JC.Systems biology:metabonomics.Nature 2008;455:1054-1056.
5.Luo HL,He ZY,Feng B,Du SP,Qi WF,An YQ.The regulation of c AMP,c GMP in b FGF gene expression in rat myocardial cells.Chin J Pathophysiol(Chin)2000;16:818-820.
6.Xie J,Wang SY,Li YL.Study experimental effect of Qingre Jiangya Capsule on anti-hypertension and research the mechanism.Chin Tradit Patent Med(Chin)2012;34:137-140.
7.Huang X,Shao L,Gong YF,Mao Y,Liu CX,Qu HB,et al.A metabonomic characterization of CCl4-induced acute liver failure using partial least square regression based on the GC/MS etabolic profiles of plasma in mice.J Chromatogr B2008;870:178-185.
8.Il-Gyo C,Chi HJ.Performance of some variable selection methods when multicollinearity is present.Chemometr Intell Lab 2005;78:103-112.
9.Okuda S,Yamada T,Hamajima M,Itoh M,Katayama T,Bork P,et al.KEGG Atlas mapping for global analysis of metabolic pathways.Nucl Acids Res 2008;36:W423-W426.
10.Ding ZK,Liu L,Xu YQ.Study of arachidonic acid.Sciencepaper Online(Chin)2007;2:410-416.
11.Yang Y,Zhang ZF,Chang LL.Analysis of patients with essential hypertension TXB2 determination results.JCardiol 1986;14:31-32.
12.Zheng MQ,Huang CH,eds.Cardiovascular disease therapeutics.Beijing:People's Medical Publishing House;1989:148.
13.Yan XH.Cyclic adenosine monophosphate meglumine heart failure efficacy of the treatment of chronic pulmonary heart disease.Jilin Med J(Chin)2010;31:1392-1393.
14.Li T,Bian CY.Cyclic adenosine monophosphate short-term treatment of chronic congestive heart failure,acute exacerbation of clinical observation.J Navy Med 2007;28:214-215.
15.L u o L F,W u W H,O u Y D S.T h e e u c o m m i a o f antihypertensive ingredients and step-down mechanism.Chin Tradit Herbal Drugs(Chin)2006;37:150-151.
16.Luo HL,He ZY,Feng B.Role of cAMP and cGMP in the regulation of b FGF gene expression of rat cardiomyocytes.Chin J Pathophysiol(Chin)2000;16:818-820.
17.Huang BX,Wang DW,Wang JF.Research advance in polyunsa-turated fatty acid.Agric Eng Tech 2009;8:26-30.
18.Sun SG,Wang YP.Research on blood pressure regulation of kidney.Chin J Evid Based Cardiovasc Med(Chin)2008;1:56-58.
19.Lu ZY,Zhong NS,eds.Internal medicine.Beijing:People's Health Publishing House;2008:252-253.
20.Wen Y,Wang HW,Lu HL,Hu XF,Shi H,Yang Y,et al.Fatty acid-induced insulin resistance in 3T3-L1 adiposities.Chin J Pathophysiol(Chin)2007;23:543-547.
21.Zhou LY,Cao MF,Wang H,Feng L,Ding H,Wei XB,et al.Protective effects of moderate ethanol consumption onβ-cell dysfunction induced by palmitate.J Shandong Univ Health Sci(Chin)2011;49:9-14.
22.Wu LL,ed.Cardiovascular pathophysiology.Beijing:Beijing Medical University Press;2005:63-64.