OBJECTIVETo study the effects of iptakalim (Ipt), an ATP-sensitive potassium channel opener, on cardiac remodeling induced by isoproterenol (ISO) in Wistar rats.

METHODSISO was given subcutaneously (85 mg/(kg x d), sc, 7 days) to induce cardiac remodeling in rats. The rats in Ipt treated group were administrated with Ipt 3 mg/kg (po) after ISO injection. After treated with Ipt for 6 weeks, the hemodynamic parameters were tested by an eight channel physiological recorder (RM-6000). Then the heart weight was weighed and the cardiac remodeling index was calculated. HE stain and Masson's stain were employed to perform histological analysis, the hydroxyproline(Hyp) content in cardiac tissue was detected by colorimetric method, radioimmunoassay was used to measure the plasma levels of endothelin-1 (ET-1) and prostacyclin (PGI2).

RESULTSSix weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group. The characteristics of ventricular remodeling in model group included that the heart weight index, myocyte cross-sectional area, myocardial fibrosis, and the hydroxyproline content in cardiac tissue were all increased significantly. The plasma level of ET-1 was increased, while the plasma level of PGI2 was decreased significantly. These changes could be reversed by Ipt treatment (3 mg/(kg x d) for 6 weeks).

CONCLUSIONIpt can reverse cardiac remodeling induced by isoproterenol in rats. The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

Animals ; Endothelin-1 ; blood ; Hemodynamics ; Hydroxyproline ; metabolism ; Isoproterenol ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardium ; metabolism ; Propylamines ; pharmacology ; Prostaglandins I ; blood ; Rats ; Rats, Wistar ; Ventricular Remodeling ; drug effects

OBJECTIVETo screen out effective ingredients of Huangqi Decoction (HQD) on dimethylnitrosamine (DMN) induced liver fibrosis and its assembling actions.

METHODS(1) DMN solution (0. 5%) was peritoneally injected to rats to prepare the liver fibrosis model for 12 times, starting from the 1st day of modeling to the end of the 4th week. Uniform design method with 4-factor 8-level table was used to optimize the proportion of four ingredients from HQD, including astragaloside (AS), astragalus flavonoids (AF), glycyrrhizae acid (GA), and glycyrrhizae flavonoids (GF). Moreover, the changes of hydroxyproline (Hyp) content in the liver issue and the level of alanine aminotransferase (ALT) in serum were observed as screen indices, and the method of regression analysis was used to find out an optimal combination. (2) A further study for comparing and verifying the efficacy of the obtained optimized prescription was conducted by observing the changes of fibrosis pathology, the content of Hyp in the liver tissue and serum enzyme activity after medication.

RESULTSThe optimal proportion of AS and GA was 164:48. Compared with the model group, the content of Hyp in the liver tissue and the levels of ALT, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum decreased significantly, indicating the inhibiting effect of HQD and the AS/GA combination group on hepatic fibrosis formation (P<0.05). The AS/GA combination group was better than AS/GA used alone group in reducing the content of Hyp in the liver tissue and the level of ALT in serum. Furthermore, the AS/GA combination group was better than the HQD group in reducing the level of ALT in serum.

CONCLUSIONSAS and GA were effective ingredients of HQD, and the combination of AS and GA had obvious synergistic effect in reducing liver collagen deposition and decreasing serum ALT activity in DMN-induced liver fibrosis.

Alanine Transaminase ; blood ; Animals ; Dimethylnitrosamine ; adverse effects ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Hydroxyproline ; analysis ; Liver Cirrhosis, Experimental ; blood ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar

BACKGROUNDThe purposes of this study were to confirm the changes in myocardial collagen level after left ventricular assist device (LVAD) support in dilated cardiomyopathy (DCM), find the relation between these changes and prognosis, and test a practical method to assess the level of myocardial collagen.

METHODSLeft ventricular samples were collected from DCM patients with different prognosis (transplanted group n = 8, weaning group n = 10) at the time when the LVADs were implanted and again during cardiac transplantation (n = 8). The level of neutral salt soluble collagen (NSC) and acid soluble collagen (ASC) was measured by Sircol collagen assay, and that of total collagen and insoluble collagen (ISC) by quantification of hydroxyproline (Hyp). Serum samples were collected from a portion of these patients (transplanted group, n = 6; weaning group n = 7) at the time the LVADs were implanted, 1 month after implantation and on explantation. Circulating concentration of carboxy-terminal propeptide of type I procollagen (P I CP), amino-terminal propeptide of type I procollagen (P I NP), amino-terminal propeptide of type III procollagen (P III NP) and type I collagen telopeptide (I CTP) were measured by the equilibrium type radioimmunoassay.

RESULTSBefore LVAD implantation the level of NSC and ISC in the weaning group was higher but ASC in the transplanted group was lower than in the controls (P < 0.05). After LVAD support, the level of total collagen was higher, but ASC was also lower in the transplanted group than in the controls (P < 0.05). In comparison of the pre- and post-LVAD subgroups of the transplanted and weaning groups, all collagen fraction levels before LVAD implantation were lower in the transplanted group than in the weaning group (P < 0.05); but this difference disappeared after LVAD support. Comparison of the pre- and post-LVAD subgroups of the transplanted group showed increased level of NSC and total collagen after LVAD support. The changes of serum peptide concentration showed that P III NP increased constantly in the transplanted group, but P I CP and P I NP increased in the weaning group after LVAD implantation.

CONCLUSIONSThe changes in myocardial collagen level as a sign of myocardial interstitial remodeling in DCM are not involved with total collagen but involved with collagen fractions, and they are related to prognosis. The changes of myocardial collagen content and serum procollagen peptide after LVAD support can be regarded as an expression of the reverse of maladaptive myocardial interstitial remodeling.

Adult ; Cardiomyopathy, Dilated ; physiopathology ; therapy ; Collagen ; analysis ; Female ; Heart Transplantation ; Heart-Assist Devices ; Humans ; Hydroxyproline ; analysis ; Male ; Middle Aged ; Myocardium ; chemistry ; Procollagen ; blood ; Prognosis

The purpose of the present study is to explore the effect of aliskiren on the proliferation of cardiac fibroblasts (CFs) in AGT-REN double transgenic hypertensive (dTH) mice. The cultured CFs from AGT-REN dTH mice were divided into AGT-REN group (dTH) and aliskiren group (ALIS). Cultured CFs from C57B6 mice were served as control (WT). The effect of different concentration of aliskiren (1 × 10, 1 × 10, 1 × 10, 1 × 10mol/L) on CFs proliferation was determined by MTT assay. After treatment with 1 × 10mol/L aliskiren for 24 h, α-SMA, collagen I, III and NADPH oxidase (NOX) protein expression in CFs of AGT-REN dTH mice were detected by Western blot. The collagen synthesis in CFs was assessed by hydroxyproline kit. The expression of ROS was determined by DHE. Results showed that the blood pressure and plasma Ang II levels were significantly increased and CFs proliferation was significantly increased as well in AGT-REN dTH mice compared with WT group. However, aliskiren intervention decreased CFs proliferation, myofibroblast transformation, as well as the collagen I and III synthesis in CFs of AGT-REN dTH mice. Meanwhile, aliskiren inhibited ROS content and NOX2/NOX4 protein expression in CFs of AGT-REN dTH mice. These results suggest that aliskiren decreases the cell proliferation, myofibroblast transformation and collagen production in CFs of AGT-REN dTH mice, which might be through inhibition of oxidative stress response.
Amides ; Animals ; Blood Pressure ; Cell Proliferation ; Cells, Cultured ; Collagen ; Collagen Type I ; Fumarates ; Heart ; Hydroxyproline ; Hypertension ; Mice ; Mice, Transgenic ; Myocardium ; Myofibroblasts ; NADPH Oxidases

OBJECTIVETo investigate the effects of Corbrin Shugan capsule on dimethylnitrosamine (DMN)-induced hepatic fibrosis in rats.

METHODSHepatic fibrosis was induced by DMN in AD rats. The serum concentrations of III pro-collagen (III PC),laminin (LN) and tissue inhibitor of metalloproteinase-1(TIMP-1) were determined with ELISA. The concentration of albumin (ALB) in sera and the content of hydroxyproline (Hyp) in liver tissues were determined with chemical colorimetric and HPLC, respectively. The fibrosis area was measured with Motic Med 6.0 digital medical image analysis system.

RESULTSCompared to model group the high-dose (450 mg kg(-1)),mid-dose (270 mg kg(-1)) and low-dose (90 mg kg(-1)) groups of Corbrin Shugan capsule had significantly lower serum content of III PC [34.46 ± 13.95),(36.15 ± 9.46), and (40.58 ± 7.72)ng ml(-1) compared with (49.38 ± 10.95)ng ml(-1),P<0.05 or P<0.01],TIMP-1 [(16.65 ± 4.24),(16.66 ± 4.34),and (18.99 ± 6.05)ng ml(-1) compared with (30.84 ± 14.48)ng ml(-1), P<0.05 or P<0.01], LN [(12.94 ± 4.29), (12.96 ± 3.21),and (15.32 ± 8.00)ng ml(-1) compared with (30.22 ± 17.00)ng ml(-1),P<0.05 or P<0.01] and smaller hepatic fibrosis area [(0.02240 ± 0.01337), (0.02176 ± 0.01460) and (0.02384 ± 0.01405)μm(2) compared with vs (0.03929 ± 0.01732)μm2, P<0.05 or P<0.01]; the high-dose and mid-dose groups of Corbrin Shugan capsule had significantly lower content of Hyp in liver tissues [(0.77 ± 0.09) and (0.81 ± 0.09)μg μmg(-1) compared with (1.06 ± 0.33)μg mg(-1),P<0.05 or P<0.01]; and the high-dose group of Corbrin Shugan capsule significantly increased the content of ALB in sera [(34.02 ± 4.17)g L(-1) compared with (30.25 ± 4.21)g L(-1),P<0.05].

CONCLUSIONCorbrin Shugan capsule is effective in treatment of DMN-induced hepatic fibrosis in rats.

Albumins ; metabolism ; Animals ; Capsules ; Collagen Type III ; blood ; Dimethylnitrosamine ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Laminin ; blood ; Liver Cirrhosis, Experimental ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo investigate the therapeutic effect of Corbrin shugan capsule for treatment of alcoholic hepatic fibrosis in rats.

METHODSThe rat model of alcoholic hepatic fibrosis was induced by intragastric administration of alcohol repeatedly. The serum procollagen III (PC III), laminin (LN) and tissue inhibitors of metalloproteinase-1 (TIMP-1) levels were measured with ELISA, and the content of hydroxyproline (Hyp) in liver tissue were determined with colorimetric method. Collagen deposition in liver tissue was observed with Masson's staining, and the fibrosis area was measured with digital medical image analysis system (Motic Med 6.0).

RESULTSCompared with the model control group, the serum TIMP-1 and LN levels and hepatic fibrosis area in liver tissue significantly decreased in Corbrin shugan capsule groups with doses of 0.09,0.27 and 0.45 g*kg(-1), and the serum PC III and the Hyp contents in liver tissue also decreased of Corbrin shugan capsule groups with doses of 0.27 and 0.45g*kg(-1).

CONCLUSIONCorbrin shugan capsule can decrease serum PC III, TIMP-1 and LN levels and Hyp levels in liver tissue and hepatic fibrosis area in rats, indicating it may have therapeutic effect on alcoholic hepatic fibrosis.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Laminin ; blood ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Alcoholic ; drug therapy ; metabolism ; pathology ; Male ; Procollagen ; blood ; Rats ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.

METHODRat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.

RESULTCompared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.

CONCLUSIONAbnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.

Animals ; Brain Ischemia ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fructose ; blood ; Glyceric Acids ; blood ; Hydroxyproline ; blood ; Lactic Acid ; blood ; Leucine ; blood ; Male ; Malonates ; blood ; Metabolomics ; methods ; Pyruvic Acid ; blood ; Rats ; Rats, Sprague-Dawley ; Stroke ; blood ; drug therapy ; Taurine ; blood ; Tryptophan ; blood

OBJECTIVETo observe the effect of Fuzheng Jiangan formula( FZJGF) on liver fibrosis using immune induced liver fibrosis rat model.

METHODThe rat models with immunity liver fibrosis were induced by the human serum albumin. Rats were treated with normal saline, FZJGF (9. 85,39. 4 g x kg(-1) , two dosage groups) and Colchicine (0. 000 1 g . kg(-1) ). The activities of ALT, AST, contents of ALB and TP, and A/G, The contents of Laminin (LN), Hyaluronic acid (HA) and collagen type IV (IV-C) in rat serum were measured by radioimmunoassay method. The level of hydroxyproline (Hyp) in liver was detected by chemistry method. The pathological changes of liver tissue were observed by HE and Von-Gieson staining.

RESULTFZJGF could significant decrease the serum activities of ALT and AST, and increase the levels of TP,Alb and ratio A/G. The levels of LN, HA and IV-C were decreased significantly after the treatment using FZJGF. The pathological improvements were observed. FZJGF could markedly alleviate the deposition of collageneous fiber, and reduce the liver pseudoluboli and the fibrosis scores in the liver tissue compared with model group.

CONCLUSIONFZJGF can inhibit formation and development of rat hepatic fibrosis induced by the human serum albumin.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Collagen Type IV ; blood ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Hyaluronic Acid ; blood ; Hydroxyproline ; metabolism ; Laminin ; blood ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; blood ; chemically induced ; prevention & control ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Serum Albumin

OBJECTIVETo study anti-atherosclerotic mechanisms of divided functional recipes of Dahuang Zhechong pill (DHZCP) in rabbits.

METHODThe atherosclerotic rabbit model was established by high fat feeding combined with immune endothelial injury. Male New Zealand rabbits were divided into 9 groups: normal control group, model control group, Danshen positive control group, and 6 DHZCP-divided groups including divided functional recipes No. 1, 2, 3 with low and high doses for each divided recipe. After intragastric administration for 60 days, blood lipids and serum MDA and NO levels and SOD activity and plasma ET concentration, and contents of hydroxyproline and proteins in the vascular wall were determined.

RESULTCompared with the model group, the level of blood lipids did not significantly change, serum MDA and ET levels, and the contents of hydroxyproline and proteins in the vascular wall significantly decreased (P < 0.05), and SOD activity and NO level increased in the divided functional recipes (all P < 0.05).

CONCLUSIONThe divided functional recipes of DHZCP can inhibit development of atherosclerosis via a non-lowering lipid mechanisms, including anti-peroxidation of lipids, protection of endothelial function, and decrease of formation of extracellular matrix by reducing synthesis of collage and protein on the vascular wall. Among them, the divided functional recipe No. 1 exhibits the most obvious effect.

Animals ; Aorta ; metabolism ; Atherosclerosis ; blood ; pathology ; prevention & control ; Cockroaches ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelins ; blood ; Hydroxyproline ; metabolism ; Lipids ; blood ; Male ; Malondialdehyde ; blood ; Materia Medica ; isolation & purification ; pharmacology ; Nitric Oxide ; blood ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation ; Rheum ; chemistry ; Superoxide Dismutase ; blood

The study is to observe the effect of racemic TJ0711 on blood pressure and heart rate as well as protection of cardiovascular system of renal hypertensive rats after long-term administration. The renal hypertensive models were established by the two-kidney, one-clip (2K1C) method in Wistar rats. Four weeks later, assigned the rats whose SBP had increased at least 4 kPa randomly into 5 groups: racemic TJ0711 10, 20 and 40 mg x kg(-1) groups, carvedilol control group, model group and sham group (n=10), ig administration once daily. The changes of BP (blood press) and HR (heart rate) before and after administration were measured by tail-cuff method weekly. Plasma samples of all animals were taken in 6-8 weeks, and plasma MDA as well as renin, angiotensin II (Ang II) and endothelin-1 (ET-1) levels were measured. Left ventricle was cut off after 9 weeks, and left ventricular weight index (LVWI) and hydroxyproline were measured. The significant decrease of the BP of TJ0711 40 mg x kg(-1) group was observed after TJ0711 ig administration for 4 weeks, and this effect remained till the end of the study. In 8th week, the systolic blood pressure values were: TJ0711 40 mg x kg(-1) group 18.93 +/- 1.82 kPa (vs 21.30 +/- 2.30 kPa, P < 0.05); 20 mg x kg(-1) group 20.68 +/- 3.29 kPa (vs 22.19 +/- 2.88 kPa). The plasma MDA level of all treated groups was significantly lower than that of model group, so were the plasma renin, Ang II and ET-1 levels (P < 0.05). LVWI and hydroxyproline content of myocardial tissue decreased to some extent, but was not significant as compared with that of model group. The study showed that TJ0711 repeated dosing could reduce BP level beginning from drug administration; besides block adrenal alpha and beta receptors to play an antihypertensive role. The sustained antihypertensive effect also related to reduce plasma vasoconstrictor substances and oxidation product MDA. These effects benefited cardiovascular protection.
Angiotensin II ; blood ; Animals ; Antihypertensive Agents ; administration & dosage ; pharmacology ; Blood Pressure ; drug effects ; Endothelin-1 ; blood ; Female ; Heart Rate ; drug effects ; Heart Ventricles ; metabolism ; pathology ; Hydroxyproline ; metabolism ; Hypertension, Renal ; blood ; physiopathology ; Longitudinal Studies ; Male ; Malondialdehyde ; blood ; Organ Size ; drug effects ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Renin ; blood