| Objective： Atherosclerosis (AS) as the arterial intima of a chronic inflammatorydisease, is one of the important reasons for the current human death. To explorethe pathogenesis of initiating factors, prevention and treatment of atherosclerosis diseasehas become the focus and hot field of medicine in the world. Endothelial cell dysfunction isone of the important causes of cardiovascular diseases such as atherosclerosis. Cellautophagy is a physical phenomenon under the pressure of hunger, lack of energymetabolism. Moderate levels of autophagy can protect vascular endothelial cells againstenvironmental stress. Therefore, vascular endothelial cell autophagy regulation mayprovide new strategies for prevention and treatment of atherosclerosis. This experimentchosen baicalin monomer as experimental drug, the apoE-/-mice were given high fatdiet made AS animal model, to observe the effect of Baicalin on the developmentof atherosclerosis and plaque stability in apoE-/-mice, and to study the intervention ofatherosclerosis study molecular mechanism of autophagy.Methods： This experiment was divided into two parts, the first part is thedevelopment of Baicalin on apoE-/-mice atherosclerosis and plaque stability, for thepurpose of baicalin has the protective effects on atherosclerosis; the second part for thedevelopment of Baicalin on atherosclerosis in apoE-/-mice of autophagy learn specificresearch, aims to autophagy to study molecular mechanism of Baicalin in treatingatherosclerosis.Measurement of autophagy in the endothelium of aorta: The level ofautophagy in aortic ECs was assessed by transmission electron microscopy. Theintracellular punctum distribution of autophagy marker the content of microtubuleassociated protein light chain3(LC3) was analyzed by en face immunofluorescencestaining. Analysis of protein levels in the endothelium of aorta: The protein levels of p62in the endothelium of aorta through frozen section immunity fluorescence staining method.Result:(1) Oil-red O staining revealed significantly lower lipid-positive area withboth high-and low-dosage baicalin than control treatment in apoE-/-mice;(2) H＆Estaining showed: baicalin treated mice aortic sinus and the brachiocephalic artery intimalumen ratio was less than the control group;(3) Oil red O staining showed: baicalin treatedmice aortic sinus lipid plaque accumulation than the control group;(4) Masson collagenfiber staining showed: baicalin treated aortic sinus place plaque collagen content than thatof control group;(5) Immunofluorescence results showed: macrophage content in baicalintreated mice aortic sinus plaque is smaller than that of the control group, smooth musclecell content than that of control group;(6) Transmission electron microscopy revealedautophagy activation in the aortic endothelium of baicalin treated mice, as shown by anincrease in autophagosomes;(7) En face immufluorescence analysis of LC3in theendothelium and quantified the average number of LC3puncta per cell. The results showedthat the number of LC3puncta was significantly increased by baicalin treatment.(8)Immunofluorescence analysis showed that p62protein level was increased in endotheliumof advanced atherosclerotic plaques, and baicalin inhibited this increase obviously. Insummary, Baicalin can effectively inhibit the development arteriosclerosis of apoE-/-mice;improve the stability of atherosclerotic plaque； enhanced autophagy throughimproving LC3and suppressing the expression of p62in endothelial cells, thus theintervention of atherosclerosis.Conclusion: Baicalin can inhibit the development of atherosclerotic plaques inapoE-/-mice;baicalin can enhance the stability of atherosclerotic plaque in artery ofapoE-/-mice;Baicalin can promote endothelial cell autophagy in apoE-/-mice;baicalinmay not affect the expression of LC3-Ⅱcontent and p62in aortic smooth muscle, mayhave no effect on the smooth muscle cell autophagy, also need further experimental testing.Summary in this study, we demonstrated that baicalin can inhibit the development ofatherosclerosis and enhance stability of the plaque, and the inference and its possiblemechanism is through the specific expression of baicalin enhanced autophagy, so that thecells can damage components to remove their own through autophagy appropriatelyenhanced, to protect the plaque cells against various stress, in order to control the fallingoff of the development of atherosclerosis and plaque, played a positive role in treatment of.It can provide the basis for the study of molecular level related to the future clinical trials. |
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