| Background and objective：Cyclooxygenase (COX) is the rate-limiting enzyme in the metabolism of thearachidonic acid to the prostaglandins, which participate in a variety of physiologicaland pathological processes, including inflammation. As an important member of theCOX family, the expression of the Cyclooxygenase-2(COX-2) usually increasesmarkedly in the cancer and inflammatory reactions. Recently, the researches aboutthe role of the COX-2in atherosclerosis are more and more, the COX-2was foundexpressing in the smooth muscle cells,endothelial cells, and macrophages ofatherosclerosis (AS). The effect of the COX-2on vascular protection or injury isassociated with the COX-2-dependent downstream prostaglandin. In this study, Weuse Angiotensin II (AngII), Insulin (Ins) to stimulate human umbilical veinendothelial cells(HUVECs), to detect the proliferation of HUVECs, the expressionof the COX-2mRNA and protein, the expression of the prostaglandinI2(PGI2) andthe intervention of the Xuezhikang.The aim was to explore the mechanisms of theAngII, Ins in atherosclerosis and the possible mechanisms of the Xuezhikang on anti-atherosclerosisMethods：The eight groups were divided in this experiment: the control group, theXuezhikang group, the Ins group,the AngII group, the Ins+AngII group, the Ins+Xuezhikang group, the AngII+Xuezhikang group, the Ins+AngII+Xuezhikanggroup. The AngII, Ins and Xuezhikang were used to stimulate HCVECs Cultured invitro. In the group containing Xuezhikang, the cells were pretreatment2h byXuezhikang, then AngII and (or) Ins were added to incubate together.Theexperiments were divided into three steps (1) the proliferations of drugs on HUVECswere detected by Cell Counting Kit-8(CCK-8) at24,48,72h;(2) the expression ofthe drugs on the COX-2mRNA and protein in HUVECs was by quantitativereal-time polymerase chain reaction(qRT-PCR) and Western-blot at24h;(3) the expression of PGI2was detected by enzyme linked immunosorbent assay (Elisa)Results:(1) The proliferation of HUVECs: compared with the control group, theproliferation of HUVECs in the Xuezhikang group decreased at24h,48h, whileincreased at72h, but all of them had no significant statistical difference with thecontrol group (P>0.05), which means there are no cytotoxicity of Xuezhikang onHUVECs. While the proliferations of HUVECs were significantly increased in the Insgroup, AngII group, Ins+AngII group compared with control group(P<0.05), and theproliferation increased more significantly in the Ins+AngII group compared with theIns group and AngII group(P<0.05);The proliferation of HUVECs in the Ins+Xuezhikang group, the AngII+Xuezhikang group and the Ins+AngII+Xuezhikanggroup were significantly lower compared with the Ins group, AngII group and Ins+AngII group (P<0.05); the proliferation of HCVECs Cultured in vitro at24,48,72hincreased the highest at24h in the Ins group, AngII group, Ins+AngII group, Ins+Xuezhikang group, the AngII+Xuezhikang group and the Ins+AngII+Xuezhikanggroup (P <0.01)(2) The expression of the COX-2mRNA and protein: compared with the controlgroup, the expression of the COX-2mRNA and protein increased in the Xuezhikanggroup, but had no significant statistical difference (P>0.05). While in the Ins group,AngII group and Ins+AngII group, the expression of the COX-2mRNA and proteinincreased significantly compared with control group (P<0.05); compared with the Insgroup and AngII, the COX-2mRNA and protein increased more significantly in theIns+AngII group (P<0.01). And compared with the Ins group, AngII group and Ins+AngII group, the expression of the COX-2mRNA and protein in the Ins+Xuezhikanggroup, the AngII+Xuezhikang group and the Ins+AngII+Xuezhikang group weresignificantly lower (P <0.05).(3) The expression of the PGI2: compared with the control group, the expressionof the PGI2increased significantly in Xuezhikang group (P<0.05); While in the Insgroup, AngII group and Ins+AngII group, the expression of the PGI2weresignificantly lower compared with control group (P<0.05); And the expression of thePGI2decreased more significantly in the Ins+AngII group,compared with the Ins group and AngII group (P<0.01); and in the Ins+Xuezhikang group, the AngII+Xuezhikang group and the Ins+AngII+Xuezhikang group, the expression of thePGI2increased significantly compared with the Ins group, AngII group and Ins+AngII group (P<0.05).Conclusion:As demonstrated in the experiment; the Ins and AngII not only can promote theproliferation of HUVECs, but also promote the expression of COX-2mRNA andprotein, and decrease the PGI2synthesis in HUVECs; all of which have a synergisticeffect; while the Xuezhikang could not only inhibit the cell proliferation, but alsocould down-regulate the expression of the COX-2mRNA and protein and up-regulatethe synthesis of the PGI2induced by AngII and(or) Ins in HUVECs. In the study,wefound that AngII, hyperinsulinemia can promote atherosclerosis and Xuezhikang playa important role of anti-Atherosclerosis,this provides the further theoretical Theoryfor the effect of statins on anti-Atherosclerosis... |
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