Effects And Mechanisms Of Glycine On Lipoplysaccharide-induced Myocardial Cell Injury In Rat

ObjiectivesNowadays, there are lots of patients with sepsis died and the mortality increses if thepatients are found heart function injury. But the effective medication onLipoplysaccharide(LPS)-induced myocardial cell injury remains destitute. Glycine(Gly) is a cell protectant. In our laboratory, our studies showed that it was not only ananti-endotoxin agent but also a kind of effective cadiocyte protectant. The presentstudy was to investigate the effects and mechanisms of Gly on LPS-inducedmyocardial cell injury in rat.MethodsThe studies were divided into following two parts:1. The effects of Gly on LPS-induced myocardial cell injury in rat were investigated.The rat were divided into five groups randomly. They were NS group, LPS group,20%Gly+LPS group, 10%Gly+LPS group and 5%Gly+LPS group. Hemodynamicindexes of left ventricle of some rat were measureed 4 hour after LPS or saline wereinjected intravenously. Blood and myocardium of other rat were collected. SerumLDH and CK activities, the ultratructure of heart were detected.2. The mechanism of Gly on LPS-induced myocardial cell injury in rat wereinvestigated. Serum and myocardial TNFαcontents were measured by ELISA,myocardial caspase-3 activities were detected by chromatometry, and TUNEL kit wasto measure the myocardial apoptotic index.Results1. The hemodynamic indexes contain left peak-value systolic pressure(LVSP), leftventricular end diastolic pressure(LVEDP) and maximum ascending and decliningrate of left ventricular pressure(±dp/dtmax). LVSP, +dp/dtmax decresed and LVEDP, -dp/dtmax incresed in LPS group, +dp/dtmax increased and LVEDP decresed in10%Gly+LPS group compared with those in LPS group(P＜0.05). LDH and CKactivities in serum were higher in LPS group than those in NS group(P＜0.05),20%Gly, 10%Gly and 5%Gly attenuated the increment of LDH activity comparedwith LPS group(P＜0.05). Disfiguration of myofilament, condensation andmargination of chromatin, Mitochondrial engorgement and vacuolization in LPSgroup were detected by transmission electron microscope, 20% Gly, 10%Gly and5%Gly inhibited LPS-induced pathological changes of myocardium.2. Serum and myocardial TNFαcontent were higher in LPS group than that in NSgroup(P＜0.01), 10%Gly and 5%Gly attenuated the increment of TNFαcontentcompared with LPS group(P＜0.05). Myocardial caspase-3 activity were higher inLPS group than that in NS group(P＜0.01), caspase-3 activity decresed in10%Gly+LPS group and 5%Gly+LPS group compared with LPS group(P＜0.05).The myocardial apoptotic index were more in LPS group than that in NS group(P＜0.01), 20% Gly, 10%Gly and 5%Gly attenuated the increment of apototic indexcompared with LPS group(P＜0.05).Conclusion1. Gly attenuates LPS-induced myocardium systolic and diastolic functiondisturbance.2. Gly inhibites the increment of serum LDH activity in LPS group.3. Pretreatment with Gly attenuates LPS-induced myocardial ultratructure injury.4. Gly protectes myocardium agaianst LPS-induced injury via inhibiting serum andmyocardial TNFαproduction, inhibiting myocardial caspase-3 activation anddecreasing myocardial apoptotic index.