Loulu The Formation Mechanism Of Inhibition Of Monocyte-derived Foam Cells

Atherosclerosis is the major pathological progress in the cardio-cerebro vascular disease. It isalso well-known that atherosclerosis is closely related to lipoprotein metabolism. In particular,oxidative modification of low density lipoprotein (LDL) cholesterol, is involved in earlydevelopment of atherosclerotic lesions through the formation of macrophage-derived foam cells.These foam cells, which are a typical feature of atherosclerotic lesions, are characterized bymassive amounts of cholesterol esters. Cholesterol accumulation in these cells have beendemonstrated to be mediated primarily by uptake of oxidized low density lipoprotein (oxLDL)via scavenger receptors, which unlike LDL receptors, are not downregulated by the celluar contentof cholesterol. CD36 , thought to be important receptors for oxLDL, belongs to the class Bscavenger receptor family. A critical regulator of CD36 expression is the nuclear hormonereceptor PPARγ can be upregulated during the formation of macrophage-derived foam cells . Theincreased expression of CD36 on the cell surface leads to the recruitment of monocytes from thecirculation further the internalizationof oxLDL. Furthermore, the differentiating macrophages andoxLDL may promote the development of atherosclerosis. Thus, macrophage, oxLDL and CD36play important roles in the formation and development of atherosclerosis. They have been thefocus of research for many years. We have found the contract of rhaponticum uniflorum can be inhibit the formation anddevelopment of atherosclerosis in animal models, and we also found ecdysterone, the maincomponent in the root of rhaponticum uniflorum. In order to find the mechanism and the potentialcomponents of the contract of rhaponticum uniflorum for the treatment of atherosclerosis, Westudy the uptake of oxLDL and the expression of CD36 in foam cells in the followingexperiments. Our experiments included three parts. First, we used fluorescein isocyanate (FITC) to label oxLDL . After incubation of U937cells with different concentrations of labelled oxLDL, flow cytometry was applied to measure thecelluar uptake of oxLDL , and microscope to observe the configuration of the cells at the sametime. We found the increasing uptake of oxLDL was associated with the increasing concentrationsof oxLDL from 10ug/ml to 80ug/ml, and the cells incubated with 80ug/ml oxLDL uptook moreoxidized LDL than others P<0.05 . However, when we increased the concentrations of oxidizedLDL from 80ug/ml to 160ug/ml, we didn't find the increasing uptake of oxLDL P>0.05 butmore injuried cells P<0.05 . Therefore, we choose 80ug/ml of oxLDL for the subsequentpharmacodynamics study. Second, We observed the uptake of oxLDL by U937 cells treated with drug dog serum ofdifferent concentrations and different time after feeding it with rhaponticum uniflorum. We used英文摘要 -5-four concentrations of drug dog serum (5%,10%,15%,20%) to inhibit the celluar uptake ofoxLDL . In contrast with the same concentrations of dog serum control, 15% and 20% of drug dogserum have the significant effects P<0.05 . Based on this result, We observed the different effectsof dog serum at 1.5h, 3h,6h,12h,24h after feeding it with rhaponticum uniflorum. The 1.5h, 3h,6hdrug dog serum showed significant effects P<0.05 . In the experiment, we also observed theuptaken oxLDL by U937 cells treated with four concentrations of ecdysterone(25 50 100200mg/l). However, we did not find that ecdysterone inhibited the uptaken oxLDL by U937 cellsP>0.05 . According to the experimental data , we deduce that rhaponticum uniflorum caninhibit the macrophage uptake of oxLDL and reduce the formation of atherosclerosis, however,ecdysterone had no significant effect on the formation of foam cells. And in the third experiment, we replicated the monocyte-derived foam cell model byincubating U937 cells with 80ug/ml oxL...