| Lysophospholipids acid is a kind of bioactive phosphatide, through the homologous G protein-coupled receptor activity inspired a complex sequence of different cells reaction,which plays a main role in cells growth, differentiation, inflammation, immune adjustment and apoptosis, etc. In blood circulation, the homopolymers relative to physiology contain LPA. The biological efficiency performance in three main aspects of vascular development including vasculogenesis, angiogenesis, and vascular maturation. In addition, in the process of formate sub prime vascular structures of the blood brain barrier, LPA also play an important role in signaling, blood vessel function and the disease.In a series of animal experiments and independent cell culture experiments, the studies show that LPA becomes the main factor in maintain circulation system normal physiological function and damage the steady-state response. The evidence for the roles of LPA signaling in the formation of secondary vascular structures considered, in accordance with important roles for LPA signaling in vascular development, function and disease.Hypoxic injury of cells is the initial steps of hypoxic-ischemic disease which also be related to the duration and severity of hypoxia. As a trigger factor impact on myocardial cell function and stability, when the myocardia loxygen demand increases, these structural abnormalities and functional changes leading to myocardial blood supply can not be a corresponding increase and it induce various types of arrhythmia and ischemic cardiomyopathy.In the myocardial cell level, the performance of the membrane integrity has been destroyed and show the abnormalities effect in electrophysiology, mechanical function and biochemical metabolic. The studies about acute myocardial infarction which show hypoxia-ischemia could led lead to heart disease and the activity of phospholipase increased with the subsequent phosphatidylinositol-bisphosphate hydrolysis and generation of multiple second messengers leading to protein kinase C activation and changes can increase LPA levels through activities of PLAs. And combined with the Gi protein activation of Gi/extracellular signal-regulated kinase pathway induced hypertrophic response signaling mechanism to promote the protein synthesis of neonatal rat cardio myocytes; for myocardial cell growth in vitro LPA through by receptor LPA3, promote proliferation play a biphasic regulation.When there is hypoxia-ischemia, Ca2+-mediated phenomenon plays an important role, calcium ion channel plays a main role on the membrane protein of cardiac muscle cell. Voltage dependent calcium channel is a type of transmembrane hetero dimers in the cell membrane open and voltage polymer protein, it connects changes of cellular energy to the electrical activity. L-type calcium channel is the most common type and involved in a variety of important physiological functions about myocardial cells.Neonatal rat ventricular myocytes cultured under hypoxic conditions and normal cultured cells compared to the damage changes and intensified with the prolongation of hypoxia time. Patch-clamp technique to record the action potential of normal cells and hypoxia cultured cells can be observed to hypoxia for different time, the action potential parameters extend the ischemic time significantly reduced. And cultured for24hours in ventricular myocytes as an example to hypoxia observed in the dose and high-dose LPA can increase ischemia-induced action potential duration shortened,24H+0.1:APA increased by1.09%, APD50increased by1.15%, APD90increased by3.03%.24H+1.0:APA increased by9.18%, APD50increased by15.21%, APD90increased by13.37%.24H+10:APA increased by13.77%, APD50increased by19.90%, APD90increased by15.22%.Experimental observations confirm the voltage control of the control group will remain inthe-50to+30mv command voltage-50mV step command is set to+10mV, the duration of200mS, calcium channel in primary cultured neonatal rat ventricular cells calcium channel is activated when depolarized to-40mV, the maximum inward peak sodiumcurrent at0mV(-3.95±0.33pA/pF). Ischemic hypoxia24H neonatal rat ventricular myocytes ICa-L peak current is significantly reduced from normal control of-3.251±0.31pA/pF to-2.51±0.23pA/pF reduce to22.8%(n=6,P<0.01). Normal ICa-L current-voltage relationship was bell-shaped OmV for the activation voltage. Ischemia and hypoxia cultured24H, ICa-L Ⅳ curve shifted upward significantly in the-20to-40mVtest voltage range, compared both with the control value significant difference (P<0.05～0.01, n=6), the shape of the curve no significant change. Description of the LPA partially protected against ischemic hypoxia on ICa-L inhibition and, consequently, the state of myocardial ischemia and hypoxia, effective refractory period of myocardial cells, excitement-contraction coupling and mechanical contractile function of maintaining a certain extent. |
