| BackgroundWith the gradually increasing age, many important organs may have retrogression changes. The compensation abilities of the organs decrease, or even long at the edge of decompensation. In clinic, pulmonary infection is common in elderly people, which is the motivation or important causes of multiple organ failure in elderly (MOFE). In MOFE patients, the myocardium is severely injured, and the mobidity of heart failure(HF) is relatively high, especially with a high rate of sudden death. There are several reasons for the decrease of myocardium contraction ability, such as free radical injury, energy metabolism dysfunction and the calcium overloading, the last one is the direct factor which determines the contractility of myocardium. The number of the papers about calcium transport and the changes of the quantity of relative proteinum and mRNA are small in MOFE patients. We made elderly rats model to observe the changes of the heart function and investigate the relative mechanism.ObjectiveWe want to make elderly rat model, and administer the rats with lipopolusac-charide(LPS) to have acute injury of the lung, and to observe the function and morphology changes of the heart and lung, the free radical injury, energy metabolism dysfunction and the calcium overloading. We also analyze the quantitative changes of the relative proteinum and mRNA, such as Ryonadine receptor, sarcoplasmic reticulum calcium ATP-ase and Na+/Ca2+ exchanger.Materials and Methods1. The functional changes of the heart of the elderly rats with LPS induced acute lung injureryA total of 120 male adult rats weighed from 250～450g were perchased from Experimental Animal Center of 301 hospital. Half of them (60) were served as adult group, and 20 of them were given NS, another 20 were only given LPS(6mg/kg), and the other 20 were given LPS and hexadecadrol(2mg/kg). The other half of the rats were given D-galactose(125mg/kg), and 20 of them were given D-galactose only, 20 were given D-galactose and LPS, and another 20 were given D-galactose and LPS and hexadecadrol. There are 6 groups: adult group, adult+LPS group, adult+LPS+hexadecadrol group, D-galactose(elderly) group, D-galactose(elderly)+LPS group, and D-galactose(elderly)+LPS+hexadecadrol group. Twelve rats in each group were selected to observe the haemodynamics and the morphology changes of the heart and lung. Heart rate(HR), left ventricular end-diastolic phase pressure(LVSP), left ventricular systolic pressure(LVEDP), the maximal rate of the increase of left ventricular pressure(+dp/dtmax) and the maximal rate of the decrease of left ventricular pressure(-dp/dtmax) were recorded. The quantity of malondialdehyde(MAD) and superoxide dismutase(SOD) were tested. The morphology of heart and lung were observed. Eight rats in each group were selected to observe the concentration of calcium in the cadiocyte with the laser con-focal microscope.2. The direct injury of LPS to the cardiocyteCardiocyte of neonate rat were segregated, then were hasten to be elderly with D-galactose (10g/L), and were separately cultured with LPS(1ng/ml) and TNFa. The concentration of calcium were tested with laser con-focal microscope.3. The abnormal expression of proteinum relative to the calcium transport in myocardial cellWe observed the abnormal expression of Ryonadine receptor, sarcoplasmic reticulum calcium ATP-ase and Na+/Ca2+ exchanger with Western blot and RT-PCR method.Results1. The heart function and biochemistry changes in elderly rats with acute lung injury induced by LPSWe made the elderly rats model with D-galactose for 6-8 weeks, and the adult or elderly rats were given LPS for 6 hours to make the lung injury rat model. The lung pathological section of the LPS processed adult and the elderly rats showed blood congestion, hydrops and inflammatory cell infiltration, and the adult control group without these changes. Hypoxemia were observed both in the LPS processed adult rats and the elderly rats, partial pressure of oxygen(PaO2) were lowered significantly(P<0.05). The heart function and the contraction ability of the LPS processed adult rats were lower than the adult control group rats significantly(P<0.05). The free radical injury of LPS processed elderly rats was more severe than the adult control rats(P<0.05). The electron microscope of LPS processed elderly rats showed the damages of the mitochondrion and the myofilament, and there were no such changes in the adult control rats. The concentration of calcium in the myocyte of the LPS processed elderly rats myocyte is higher than that in the adult rats. All these changes were inhibited by hexadecadrol, which protected the heart function and lung tissue injury in elderly rats.2. The direct injury of LPS to the cardiocyteContrast with the control group, D-galactose processed elderly rats has little change in the concentration of calcium in the myocytes, D-galactose and TNF(200μl), D-galactose and LPS processed elderly rats has significant increase the concentration of calcium in the myocytes respectively, the former is moresevere than the later. These results indicate that LPS can increase the concentration of calcium in the elderly rats myocytes and has direct injury to the myocytes.3. The abnormal expression of proteinum relative to the calcium transport in myocardial cellIn the adult and elderly rats, the quantity of the calcium transport related protein in the myocytes had significantly changed, the quantity of mRNA of the RYR2 decreased, the quantity of mRNA and protein of NCX1 increased, and the quantity of mRNA and protein of SERCA2a decreased.Conclusion5.1 The heart function of the D-galactose processed rats decreased obviously, which is caused by the free radical injury, the energy metabolism dysfunction and the overloading of calcium in the myocyte.5.2 LPS can increase the concentration of calcium in the D-galactose processed rats myocyte directly.5.3 The heart function and the quantity of mRNA of the RYR2 decreased, the quantity of mRNA and protein of NCX1 increased, and the quantity of mRNA and protein of SERCA2a decreased, which is the main reason contribute to the cardiac dysfunction in elderly rats. |
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