| Lysophosphatidic acid is a intermediary metabolite of phospholipid in cell membrane, it also releases from activated platelets. Through the clinic epidemiology investigation about incidence of arrhythmia in ovary cancer, We observed that the incidence rate of arrhythmia of ovary cancer and hepatoma were 32.38% and 10.19% respectively. This result suggests that LPA may involve in arrhythmia occurance.Lysophosphatidic acid has a wide spectrum of biological effects on variety cells via G-protein-coupled cell surface receptors. More studies focused on the role of LPA in physiological and pathological processes. During the course of acute myocardial infarction, the number of white blood cell increased, inflammatory cell infiltration were surrounding the coronary blood vessels, and various of cytokines was significantly increased. This suggests that AMI is a process of immune inflammatory response, inflammatory cell and various of cytokines played an important role of the induction of arrhythmia.Connexin 43 is the gap junction channels of the ventricular myocytes.If connexin 43 was reduced by 50%, the interior of the heart conduction slowed down, leading to arrhythmia. We use the immune-enhancing and immunosuppressive drugs (thymopeptide and cyclophosphamide) to interfere with the immune system of laboratory animals for 8 days, leukocyte in peripheral blood will be accoutted to confirm the immune enhancement or immune suppression . Ligating lower left branch of the left coronary artery of rats , then injecting intravenous lysophosphatidic acid into the heart surface, and recording the lantency of arrhythmia incidence. We found ,in immune-enhancing group of animals with lysophosphatidic acid injection, the arrhythmia occurred earlier than the normal control group, the incidence rate of arrhythmia significantly increased, on the other hand, immune suppression group with injection of lysophosphatidic acid, arrhythmia occurred later than the normal control group, the incidence rate of arrhythmia also decreased significantly. It proved that the effect of Lysophosphatidic acid on arrhythmia is highly related with the immune system situation. when the body's immune system was suppressed, the incidence rate of arrhythmia will decrease.We cultured human T lymphocytes (Jurkat T), add in the culture medium lysophosphatidic acid, collecting of culture medium timingly, then using double-sandwich ELISA method to analyze the tumor necrosis factor (TNF) concentration in the culture medium. the results proved that lysophosphatidic acid can activate Jurkat T lymphocytes, induce TNF-αgene expression, then promote of TNF-αsynthesis and release.The voltage dependent potassium channels [K (v)]and calcium-activated potassium channels [K (Ca)] characteristics of the Jurkat T cells are studied by Patch-clamp technique. Studies have shown that lysophosphatidic acid can increases K (v) channel current of Jurkat T cells, promoting of K + influx, K (Ca) channel conductance increased, that means the number of channels increased, further evidence of lysophosphatidic acid-activated Jurkat T lymphocytes, inducing by TNF-αgene expression, the promoting of TNF-αsynthesis and release is the role of Jurkat T lymphocytes by activating membrane K (v) channels and K (Ca) channel to the implementation.Of our in vivo animal model of acute myocardial infarction (including blank control group, normal control group, immune-enhancing group and immune suppression group) of the heart, by immunohistochemical staining method was used to observe the expression of Cx43 and found that: myocardial infarction after injection of exogenous LPA of the animals, Cx43 expression in ventricular myocytes than normal animals decreased immunoenhancement animals decreased the expression of Cx43 is more obvious, and the immune suppression of animals the expression of Cx43 is similar to normal animals, LPA specific blocker may be partially blocked LPA so that the decline in the role of Cx43 expression. It prove that LPA caused the degradation of Cx43 and decreased expression, which may be arrhythmogenic LPA an important way.The above results suggest that: LPA involved in acute myocardial infarction after the occurrence of arrhythmia, the mechanism of immune regulation are the releasing of cytokines and implementation by inflammatory cells, our experiments prove that LPA can activate T lymphocytes, release of cytokines TNF, then inhibit the expression of Cx43 ,and all of above can increase the occurrence of arrhythmia.
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