Effect Of Ginsenoside-Rb3on Ventricular Remodeling In Rats With Pressure Overloaded Hypertrophic Myocardium And Its Mechanism

Ventricular remodeling, which is caused by a series of molecular and cellularmechanisms, is the changes of cardiac structure, function and phenotype, including myocytehypertrophy, apoptosis, quality and qualitative changes of myocardial extracellular matrix.It’s one of the basic mechanisms of heart failure. There are several important causes ofventricular remodeling: cardiac overload, excessive activation of the renin angiotensinsystem(RAS), the stimulation of endothelin, decrease of blood vessel relaxation factor, highoxidative stress level and the broken balance of some blood vessels activating factors.Araliaceae American Ginseng(Panax quinquefolium L.), which is wildly grown in theChangbai Mountain, has long been known as a root medicine, and the leaves and stems usedto be abandoned. The effective parts of American ginseng are ginsenosides, which are alsofound in the leaves and stems of American Ginseng. Our team, cooperating with the NaturalMedicinal Chemistry Laboratory of the former NBUMS, had done systematic chemistry andpharmacology research of the leaves and stems of American Ginseng. We developed a newdrug of Chinese Medicine Type IV for angina pectoris, Xinyue Capsule, with the PanasQuinquefolium Saponin(PQS), that changed waste material into things of value. Furtherresearch proved that Panas Quinquefolium20s-Protopanoxadiol Saponin (PQDS) is one ofthe effective ingredient of PQS. So we extracted PQDS from PQS, and developed anothernew drug of Chinese Medicine Type V for myocardial ischemia, PQDS Injection.Ginsenoside Rb3(G-Rb3), accounting for about40%, is one of the main monomercomponents of PQDS, and it can be a potential new drug of Chinese Medicine Type I.Our previous research has proved that G-Rb3has many pharmacological effects. It cansignificantly extend the survival time of oxygen deficit mice with Isoproterenol i.h.; it cansignificantly recover the the abnormal ECG of rats which had myocardial ischemia causedby Pituitrin i.v.; it can reduce the injury of myocardial ischemia in rats with Isoproterenol i.h.,ameliorate the hemodynamic parameters of them, decrease the MDA content in myocardiumand the activity of LDH and CK in serum, increase the activity of SOD and CAT inmyocardium; it can reduce the damage of oxygen radicals, ET and AngII, attenuate themyocardial infarct size, reduce the pathological damage of myocardium in myocardial ischemia and reperfusion rats; it can inhibit the proliferation of vascular smooth muscle cellsinduced by AngII, inhibit the cell cycle from G0/G1phase to S phase, attenuate theexpression of proto-oncogene c-myc, c-fos and c-jun; it can attenuate the ventricularremodeling in myocardial infarct rats, and its probably mechanisms include inhibiting RAS,reducing the damage of vasoconstrictor substances in myocardium, enhancing antioxidantcapacity of myocardium. The effect of G-Rb3on ventricular remodeling with pressureoverloaded hypertrophic myocardium and its mechanism have not been reported in anypaper. In this thesis, we chose the ventricular remodeling rats model of pressure overloadedmyocardial hypertrophy induced by abdominal aortic stenosis to observe the anti-ventricularremodeling effect of long-term dosing G-Rb3, and do a preliminary study on its mechanism.Experimental method: The Wistar rats were divided into sham operation group,remodeling model group, G-Rb3low dose group, G-Rb3middle dose group, G-Rb3highdose group, captopril group. Each group had12rats. Built the ventricular remodeling ratsmodel of pressure overloaded myocardial hypertrophy induced by abdominal aortic stenosis.Each group is treated different drug according to different groups mentioned above. After6weeks, each group of Wistar rats were anesthetized with intraperitoneal injection of10%chloral hydrate (300mg/kg), left ventricular systolic pressure(LVSP), left ventricular enddiastolic pressure (LVEDP), maximum left ventricular presure rising and dropping rates(±dp/dtmax), systolic blood pressure(SBP), diastolic blood pressure(DBP) and heart rate(HR)were measured and the mean arterial pressure(MAP) was calculated. After the measurementof hemodynamics, the serum from abdominal aorta was measured for the content of nitricoxide(NO), malondialdehyde(MDA) and the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px); the plasma added with anticoagulant was measured for thecontent of angiotensin Ⅱ(Ang Ⅱ), endothelin(ET),6-Keto-PGF1α(for PGI2), TXB2(forTXA2) with radioimmunoassay method; the heart of rats in each group were weighed forleft ventricular absolute mass(LVAW), body weight(BW) to calculate the left ventricularrelative mass(LVRW); and then fixed the myocardial tissue with paraformaldehyde to makehematoxylin-eosin staining paraffin sections for morphological observation in optical microscope.Experimental results: Compared with the model group, SBP, DBP, MAP, LVSP, ±dp/dtmax were significantly increased while HR and LVEDP were significantly decreasedin G-Rb3middle dose group and G-Rb3high dose group, and the difference wasinsignificant in G-Rb3low dose group; the content of MDA in serum was significantlydecreased while the activity of SOD and GSH-Px in serum was significantly increased inG-Rb3middle dose group and G-Rb3high dose group; the content of TXA2in plasma wassignificantly decreased while the content of PGI2in plasma and the ratio of TXA2/PGI2weresignificantly increased in G-Rb3middle dose group and G-Rb3high dose group; the contentof ET and Ang II in plasma was significantly decreased in G-Rb3middle dose group andG-Rb3high dose group while the content of NO in serum was significantly increased inG-Rb3high dose group; LVRW was significantly decreased in G-Rb3middle dose groupand G-Rb3high dose group while LVAW was significantly decreased in G-Rb3high dosegroup. Morphological observation in optical microscope of hematoxylin-eosin stainingparaffin sections showed that: In model group, the myofilaments were thickening andarranging disorderly; edema, connective tissue proliferation and infiltration of inflammatorycells significantly existed in the myocardial interstitial; ventricular remodeling was obvious.In G-Rb3middle dose group and G-Rb3high dose group, the myofilaments were notthickening and arranging disorderly; edema, connective tissue proliferation and infiltrationof inflammatory cells insignificantly existed in the myocardial interstitial; ventricularremodeling was obviously attenuated by middle dose and high dose G-Rb3. In catopril group,the myofilaments were not thickening and arranging disorderly; edema, connective tissueproliferation and infiltration of inflammatory cells insignificantly existed in the myocardialinterstitial; ventricular remodeling was obviously attenuated by ACEI.