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The Study about the Effect of Lysophosphatidic Acid on Ischemia Hypoxia Cardiac Myocytes of Guinea Pigs

Author: HeYongFeng
Tutor: ZhaoChunYan
School: Jilin University
Course: Physiology
Keywords: lysophosphatidic acid Ischemia hypoxia Cardiac myocytes ATP-sensitive K(+) channel Mitochondrial transmembrane potential
CLC: R363
Type: Master's thesis
Year: 2009
Downloads: 50
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Abstract

Ischemic Heart Disease (IHD) is a kind of myocardial damage which results from disequilibrium between essential coronary blood flow and virtual blood flow caused by the change of coronary circulation. It is a fatal disease which imperils the whole of humankind’s health in both developed countries and developing countries. Therefore, IHD is a significant subject in medical research field. Clinical study has indicated that comparing normal control group, the concentrations of LPA in the blood of IHD patients, including myocardial infarction , angina pectoris etc, are all obviously high. Lysophosphatidic acid is an intermediary metabolite of phospholipid in cell membrane, which is the most simple glyceryl phosphatide in its structure among known ones. Many studies have shown that LPA exhibits many kind of biological functions by effecting on G-protein-coupled endothelial-cell differentiation genes (EDG) receptors in a variety of histiocyte cells . What cause the concentrations of LPA in blood to increase are as follows: During myocardial infarction, phospholipase becomes more active that enhance its cracking ability. Then it must arouses the amount of pyrolysis products in cell membrane and the concentrations of LPA in blood increased ; (2) Since activated platelets could release LPA , onset of these diseases could cause more platelets aggregated and much more LPA into blood . Moreover, EDG receptors of LPA extensively distribute in myocardium . All these hint that there is close connection between LPA and IHD.Some experiments to explore the relationship between LPA and IHD are already finished in our laboratory and the results show that exogenous LPA could inhibit myocardial cell apoptosis induced by ischemia-reperfusion. In other words, exogenous LPA might protect myocardial cells from apoptosis in the condition of ischemia and hypoxia, but the mechanism is not clear yet . What I have done in my experiment is researching on guinea pig myocardial cell in the situation of ischemia and hypoxia to explore the effect of LPA on myocardial cells in the special situation and the relative mechanisms.1. The effect of LPA on action potential of guinea pigs ventricular myocytes in the condition of ischemia hypoxia.Whole-cell patch clamp recording was adopted to record action potential in the guinea pigs’ventricular myocyte which was in the condition of ischemia hypoxia with high resistance seals. Then adding LPA(10umol/L) into the solution, record action potential at the same condition 3 minutes later . The results showed that , compared with the control group , adding exogenous LPA(10umol/L) could lead to the action potential of guinea pig ventricular myocytes decreased from 77.39±4.76mV to 69.61±4.11mV(P<0.05); the resting potential of ventricular myocytes decreased from 70.64±3.26mV to 69.47±3.52mV(P>0.05),and there was no statistical significance. And APD50 of ventricular myocyte decreased from 167.94±11.82mS to 151.62±7.28mS(P<0.05),while APD90 decreased from 198.05±9.15mS to 182.61±6.80mS(P<0.001).2. The effect of LPA on sarcolemmal ATP-sensitive potassium channel of guinea pigs’ventricular myocytes in the condition of ischemia hypoxia.Whole-cell patch clamp recording was adopted to record IKATP in the guinea pigs’ventricular myocytes which was in the condition of ischemia hypoxia with high resistance seals. Holding potential was controlled at -100mV, while the testing potential was controlled from -100mV to +100mV. And step input was 20mV, while time history was 300mS. The results showed that, compared with the control group, the current density of the LPA(0.1umol/L) group increased slightly, from 10.98±2.19pA/pF to 13.55±3.95pA/pF, but there was no statistical significance; and the current density of the LPA(1umol/L) group increased from 10.98±2.19 pA/pF to 15.23±3.26pA/pF. The change range was significant, but there was still no statistical; the current density of the LPA (10umol/L)group increased from 10.98±2.19 pA/pF to 17.89±3.99pA/pF, and there was significant statistical difference.3. The effect of LPA on mitochondrial transmembrane potential of cultured guinea pigs’ventricular myocytes in the condition of ischemia hypoxia.Cultured guinea pigs’ventricular myocytes, and divide them into the condition of ischemia hypoxia in different group at the fifth day, then tested the mitochondrial transmembrane potential of each group with flow cytometry. In this experiment, it could be found that, comparing with the control group, the MMP in the group of ischemia hypoxia decreased markedly. This trend showed that the model of ischemia hypoxia had been made successfully. It also could be found that, comparing with the group of ischemia hypoxia , the group’s MMP of ischemia hypoxia with LPA increased. This result showed that LPA can protect ventricular myocytes in the condition of Ischemia hypoxia by increasing MMP. And there is no significantly difference between the MMP of the hypoxia ischemia group and the MMP in the group of ischemia hypoxia with LPA and PTX, This result indicated that PTX could block the protection of exogenous LPA , and that LPA could protect ventricular myocytes in the ischemia hypoxia through g-protein coupled receptors.

The Study about the Effect of Lysophosphatidic Acid on Ischemia Hypoxia Cardiac Myocytes of Guinea Pigs

Abstract

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