The Mechanim Of Clopidogrel Injure Human Gastric Epithelial GES-1Cells

Aims： The MAPK/extraceilular signaling regulated kinase(ERK)signalingpathway was analyzed to clarify the damage mechanism of Clopidogrel in humangastric epithelial cell line （GES-1cells）in vitro．Methods：GES-1cells were cultured in vitro. Then the GES-1cells weredivided into four groups：1)control group，2)U0126group,3) Clopidogrel group4)U0126+Clopidogrel group; the reduced proliferation rates and apoptosis rates ofGES-1cells in four groups were examined using methyl thiazolyl tetrazolium (MTT)assay and Flow cytometry; The expression of phosphorylated ERK1/2protein inGES-1cells were detected by inmunohistochemistry method and The expression ofphosphorylated ERK1/2protein and Occludin protein in GES-1cells were detectedby Western blot.Results： The result of MTT shows that contrast to control group, theproliferation of GES-1cells was inhibited in U0126group、Clopidogrel group andU0126+Clopidogrel group:21.8%±2.7%,46.3%±3.4%,82.9%±0.8%(P=0.000);Flow cytometry analysis indicated that the apoptosis rates of cells treated with U0126,Clopidogrel and the co-injury group were higher than that in control group. The resultof immunocytochemistry examination showed that the expression of p-ERK inU0126group、Clopidogrel group and U0126+Clopidogrel group was lower than thatof control:10.80±1.64、7.20±1.64、4.40±0.89、1.40±0.55(P=0.000). Thetrend of Western blot is the same as the result of immunocytochemistry examination.The expression of p-ERK and Occludin protein in other three groups was lower thanthat of control(P<0.01). Conclusion： The injury mechanism of Clopidogrel in human gastric epithelialGES-1cells may inhibit the expression of p-ERK to decrease the expression ofOccludin.