| PurposeTo observe the expression of CXCR4 in atherosclerotic plaques ,and to observe the change of proliferation and apoptosis of SMC after adding SDF-1 to the cells on the base of ox-LDL,as well as the change of expression of apoptosis related gene bcl-2,bax , to approach the effect of SDF-1/CXCR4 axis on atherosclerosis.MethedWe checked the expression of CXCR4 by immunohistochemical method; Cells were random divided to: control,ox-LDL group(model groups),model +SDF-1 groups, model +SDF-1+12G5 groups,model +12G5 groups. Then we checked the proliferation with MTT, decect the apoptosis by TUNEL, to evaluate the expression of bcl-2/bax by RT-PCR method.Result1. CXCR4,the only receptor of SDF-1, was shown to be highly expressed in atherosclerotic plaques.2. Compared with control group, SMC proliferation and apoptosis of ox-LDL group significantly increased (P<0.05).3. After incubating SMC with ox-LDL and SDF-1((500μg/ml ) for 24 hours, SDF-1 can significantly increase proliferation of VSMC(P<0.05). The effect of SDF-1 can be inhibited by 12G5,the monoantibody of CXCR4,and 12G5 had no effet on proliferation of VSMC . 4. After Incubating SMC with ox-LDL and SDF-1((500μg/ml ) for 24 hours, SDF-1 can significantly deccrease the percent of apoptosis (P<0.05). The effect of SDF-1 can be inhibited by 12G5- the monoclone antibody of CXCR4,and 12G5 had no effet on the percent of apoptosis of VSMC .5. Compared with normal control, bcl-2,bax mRNA masculine rate and bcl-2/bax ratio in ox-LDL model group are changed(P<0.05,n=8); SDF-1group's bcl-2/bax ratio heightened than ox-LDL model group, there is statistical significance (P<0.05). The result shows that SDF-1 may influence apoptosis through bcl-2/bax pathway.Conclusion1. CXCR4 was shown to be highly expressed in atherosclerotic plaques.2. SDF-1/CXCR4 can significantly increase proliferation of VSMC,and the effect is through SDF-1/CXCR4 axis.3. SDF-1/CXCR4 can significantly decrease the percentage of apoptosis of VSMC,and the effect is through SDF-1/CXCR4 axis.4. SDF-1/CXCR4 axis may affect apoptosis of VSMC through Bcl-2/Bax.DiscussionCell proliferation and apoptosis is the cytological base in the occurrence and development to atherosclerosis. SMC proliferation is the most important character in the pathological changes of atherosclerosis,is one of the important mechanisms for the formation of atherosclerotic plaque. According to observation,the increased VSMC in the atherosclerosis plaque not only from SMC continual proliferation,but also from the complication of the reduced cell apoptosis speed and decreased cell apotosis number.Stromal cell derived factor-1(SDF-1) is a kind of chemokines,and its specific receptor is CXCR4,they form SDF-1/CXCR4 biological axis,transducting specific signal and tranformating different effect.The biological axis'key roles in the Immuno-inflammatory Response,neoplastic invasion, hematopoietic regulation and control have been approved. In recent years,it has been found that SDF-1 is highly expressed in atherosclerotic plaques,infered that it closely associates with the development and progression of atherosclerosis, but the condition of CXCR4 expression in atherosclerotic plaques is so far unknown; the recent research suggested that SDF-1,as a kind of wide-spectrum cytokine,not only has the chemotaxis,but also has role of promoting proliferation, differenciation.and inhibiting apoptosis of hematopoietic stem/pregenitor cells and leukemic cells,but the effect to SMC's proliferation and apoptosis ,has been so far unknown.Compared with fomer reseach, Our experiment discovers that CXCR4 is highly expressed in atherosclerotic plaques,and we reseach SDF-1/CXCR4 biological axis in cultured SMCs in vitro firstly,as well as the axis'effect on proliferation and apoptosis of SMC on the base of ox-LDL. Certainly,the reserch of SDF-1/CXCR4 axis'effect on occurrence to atherosclerosis is just beginning at home and abroad, the causation and concrete mechanism need further study.If we definitude the axis'indispensable position in atherosclerosis,then how to block or inhibite the axis will be a new direction of preventing atherosclerosis and coronary artery disease. |
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