| Coronary Heart Disease is one of the main cardiovascular diseases, which is caused by Coronary Atherosclerosis in most casses.Present therapies include interventional therapy, surgical treatment, drug treatment and gene therapy. Although these therapies have get good clinical efficacy in usual cases, the myocardial ischemia reperfusion injury (MIRI) and subsequent ventricular remodeling (VR) after applying them have become new disadvantages. Ginseng fruit saponins (GFS) is the ginsenosides separated from Ginseng's fruit, and is also the main effective components of Ginseng's fruit. It has proved that GFS can resist myccardial ischemia in rats and acute myocardial infarct in rats and dogs,increase myocardial alimentary blood flow in mice.But the effect of GFS on MIRI and subsequent VR has not been reported.Our research observed the effects and mechanisms of GFS on MIRI and subsequent VR through MIRI and subsequent VR model in rats, cardialcytes hypertrophy and cardiac fibroblasts proliferation model in cell.1. Effects of IGFS on MIRI in rats.1.1 MethodsRats were divided into 6 groups: sham group, MIRI model group, positive control group and GFS 5,10,20mg/kg groups. The MIRI model was induced by left anterior descending coronary occulusion for 30 minutes and reperfusion for 120 minutes in rats (except sham group). Drugs were administrated through iv just before reperfusion. Serum of 10 rats of each group was collected to detect the activity of AST, CPK and LDH. Then removed out the hearts to measure MIS by NB-T stain.The serum and plasma of other 10 rats were collected to detect the content of MDA, ET, Angâ…¡, PGI2, TXA2 and activity of SOD, GSH-PX.Then took 100mg myocardial from infarct area and non-infarce area respectively to detect the content of FFA.1.2 ResultsAll of three doses of GFS could deflate MIS in MIRI rats(P<0.05 or P<0.01); middle and high doses of GFS could decrease the activity of AST, CPK, LDH(P<0.05 or P<0.01). All of three doses of GFS could decrease the content of MDA(P<0.05P<0.001); middle and high doses of GFS could increase the activity of SOD, GSH-Px(P<0.05 or P<0.01). All of three doses of GFS could decrease the content of FFA in myocardial infarct area(P<0.05 or P<0.01); but only high doses of GFS could decrease the content of FFA in myocardial non-infarct area (P<0.05). Middle and high doses of GFS could decrease the content of Angâ…¡i n plasma (P<0.05) and had trend of decrease the content of ET in plasma (P>0.05). Middle and high doses of GFS could decrease the content of TXA2, increase the content of PGI2 and the ratio of PGI2/ TXA2 in plasma (P<0.05 or P<0.01).2. Effects of GFS on VR after MIRI in rats2.1 MethodsRats were divided into 4 groups: sham group, VR model group, positive control group and GFS 10 mg/kg group. The VR after MIRI model was induced by left anterior descending coronary occulusion for 2 hours and reperfusion for 4 weeks in rats (except sham group). Drugs were administrated for 4 weeks from the next day after reperfusion.The hearts of 8 rats of each group were removed out to measure VAW, VRW, LVAW, LVRW, RVAW, RVRW.Then took 100mg myocardial from non-infarce area to detect the content of ET and Angâ…¡. Hemodynamic parameters of the other 8 rats were examed.Then collect serum and plasma to detect the activity of SOD, GSH-Px, NOSand content of MDA, NO, Ca2+, PGI2, TXA2. HE staining,Masson staining, immunohistochemistry staining of collagenâ… ,â…¢and electron microscope detection on myocardial were adopted.1.2 ResultsGFS could decrease the volume of heart of VR rats, limit the infarct area, lower the rate of aneurysm and reduce the expansion of ventricular. GFS could increase the number of residual cardialcytes in infarct area and reduce the cytopathic around the infarct area. GFS could also reduce the myofilament dissolved,the swelling and ridge fracture of mitochondria,the pyknosis of nuclear of cell around the infarct area. GFS could decrease VAW, VRW, LVAW, LVRW in SV rats (P<0.05 or P<0.01) and had trend of decrease RVAW, RVRW (P>0.05). GFS could increase SBP, DBP, LVSP, +dp/dtmax and -dp/dtmax (P<0.05 or P<0.01) in SV rats, and had trend of increase HR and decrease LVEDP (P>0.05). GFS could decrease the serum content of MDA, increase the activity of SOD and GSH-Px (P<0.05). GFS could decrease the serum content of Ca2 (P<0.05), but have no effect on NO and NOS. GFS could decrease the plasma content of TXA2, increase the content of PGI2 (P<0.05 or P<0.01). GFS could decrease the content of ET and Angâ…¡in myocardial non-infarct area (P<0.05). GFS could reduce collagen hyperplasia around the infarct area, but its effects on collagen typeâ… ,â…¢were not be determined.3. Effects of GFS on cardialcytes hypertrophy and cardiac fibroblasts proliferation3.1 Methods3.1.1 Effects of GFS on cardialcytes hypertrophyThere were 6 groups: nomal control group, hypertrophy model group, GFS 10,20,40,80μg/ml groups. Cardialcytes from neonatal rat were cultured in vitro. 1×10-7mol/L ANGâ…¡were administrated to stimulate hypertrophy and drugs were administrated with ANGâ…¡. Collected cardialcytes after cultured for 4h to detect the express of proteins of p-ERK and c-fos by western blot. Recorded the cell surface area under inverted phase contrast mocroscope and detected the content of total protein by BCA kits after cultured for 48h.3.1.2 Effects of IGFS on cardiac fibroblasts proliferationThere were 6 groups: nomal control group, hypertrophy model group, GFS 50,100,200,400μg/ml groups. Cardiac fibroblasts from neonatal rat were cultured in vitro. 1×10-7mol/L ANGâ…¡were administrated to stimulate proliferation and collagen secretion, and drugs were administrated with ANGâ…¡. Proliferation of CFs, content of HP were detected after culture for 24h.3.2 ResultsGFS 20,40,80μg/ml could deflate myocytes'surface area (P<0.05 or P<0.001) which have a dose-dependent relationship. GFS 20,40,80μg/ml could decrease the content of total protein which have a dose-dependent relationship. GFS 20,40,80μg/ml could decrease the express of proteins of p-ERK and c-fos. No obviously effects of GFS were observed on proliferation of CFs and content of HP.ConclusionsGFS can resist MIRI through inhibiting overoxidation injury , raising blood-supply and regulating PGI2/TXA2 balance of myocardium. GFS can defense ventricle remodeling induced by MIRI through decrease the lever of modeling stimulate factors. GFS could inhibit cardialmyocytes hypertrophy induced by Angâ…¡through impacting MAPK path, but have no obviously effect on cardiac fibroblasts proliferation and collagen secretion.The mechanism is remained to research. |
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