Effect Of Matrine On Remodeling Of Hypertrophied Myocardium Induced By Pressure Overload Of SD Rats

Background:Matrine, which comes from leguminosae plants such as KuSheng, is quinoilizidine with four-loop, its molecular formula is C₁₅H₂₄N₂₀. It has been proved that Matrine has effects of anti-arrhythmia, anti-hypoxia and decreasing heart rate in many animal experiments, and the role of sedation and lower body temperature in nervous system. It has been written into Traditional Chinese Medicine Pharmacopoeia as the indication in treatment of heart failure. At present the medical therapy of heart failure has been re-recognized, only which can reverse cardiac remodeling, can finally improve cardiac function and prognosis. Many documents on animal experiments andclinic multi-center large scale evidence-based trials proved that drugs reversed heart remodeling through interfering nervous-endocrine system such as carvedilol (P -blockade) et al. Our purpose is to explore if Matrine can affect the cardiac remodeling of hypertrophied myocardium induced by over-load pressure and its certain mechanism. Group, which treated with carvedilol ( (3 -blockade), was contrast.Part I :Effect of Matrine on Hypertrophy Myocardium and Its BNPmRNA expression induced by Pressure Overload of SD RatsObjective:To explore the effect of Matrine (Mt.) on hypertrophy myocardial induced by pressure over-load and its BNP mRNA expression of SD rats. Methods:Pressure over-loaded myocardial hypertrophy was produced by banding of aorta abdominalis in male Sprague-Dawley rats weighing 200g ± 15g. The rats were assigned into one of the following groups: sham-operation control, operation control, operation group with treatment ( Matrine 15mg/kg/d or Carvedilol 3.6mg/kg/d ). The rats were administered with drugs one day after operation. 5 weeks after treatment, left ventricular weight (LVW) , H-E stain were used to assess and the volume of myocardial cell. Myocardial mRNA of BNP was semi-quantified with RT-PCR. Results:LVW/BW (body weight) (P<0.05), mRNA expression of BNP (PO.05), the size of myocardial cell obviously increased in operation group compared with sham control group. Mt. and Car. treatment can significantly decrease LVW/BW(P<0.05), mRNA expression of BNP (PO.05), the size of myocardial cell compared with operation group. But there was difference compared with sham group. Conclusions:It showed that Matrine can prevent cardiac remodeling of hypertrophy cardium induced by pressure over-load including myocardial hypertrophy and reduce mRNA expression of BNP.Part II:Effect of Matrine on Fibrosis of Hypertrophy Myocardium induced by Pressure Overload and Its Mechanism of SD RatsObjective:To explore the effect of Matrine (Mt.) on fibrosis of hypertrophy myocardial induced by pressure over-load and its mechanism of SD rats. Methods:Pressure over-loaded myocardial hypertrophy was produced by banding of aorta abdominalis in male Sprague-Dawley rats weighing 200g ± 15g. The rats were assigned into one of the following groups: sham-operation control, operation control, operation group with treatment ( Matrine 15mg/kg/d and Carvedilol 3.6mg/kg/d ) . The rats were administered with drugs one day after operation. 5 weeks after treatment, Masson stain was used to assess the level of fibrosis of myocardial matrix. Myocardial metalloproteinases activity was quantified with Zymography. TGF- P , was measured by PT-PCR, immunohistochemistry and in situ hybridization . Results:Interstitial fibrosis , MMP-2 activity (.P<0.05), TGF- j3 j expression were obviously increased in operation group compared with sham control group. Mt. and Car. treatment can significantly decrease interstitial fibrosis , MMP-2 activity (P<0.05), and TGF- ï¿¡ i expression (PO.05) compared with operation group. But there was difference compared with sham group. Conclusion:It showed that Matrine could prevent cardiac fibrosis of hypertrophied myocardium, which induced by pressure over-load, its mechanics may be associated with the decrease in MMP-2 activity and TGF- 3 i expression of heart.