Influence Of QSYQ Drop Pills On Vascular Endothelial Function In Hyperlipidemia Rats

ObjectiveTo observe the influence of QSYQ drop pills and fluvastatin on vascular endothelial function in hyperlipidemia rats after common carotid artery balloon catheter denudation,and research the mechanism.Methods1.After one week adaptive feeding,a total of70healthy male SD rats were divided into control group(n=7) and experiment group (n=63). The experiment group fed with high-cholesterol diet continuously for16weeks,then were tested the serum lipid and performed the left common carotid artery balloon catheter denudation surgery.The experiment group rats were randomly divided into Sham group(B group),Model group(C group), Model+Fluvastatin group (D group)and Model+QSYQ drop pills group(E group). The B group didn’t have the procedure of balloon catheter inserted.2. Drug intervention:Rats in E group were given QSYQ drop pills(200mg/kg) by lavage administration,rats in D group were supplemented with Fluvastatin (5.5mg/kg). A、B group and C group were given the same volume of distilled water.The durg intervention time was for8weeks.3.Serological tests:Blood was drawn from the angular vein of rats that were not fed overnight at baseline and the end of16and25week. Serum levels of total cholesterol (TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C) and high-density cholesterol (HDL-C) were detected.The serum levels of endothelin-1(ET-1),nitric oxide(NO),superoxide dismutase(SOD), malondialdehyde(MDA), thromboxan1B2(TXB2),6-keto-prostacylin F1α(6-keto-PGF1α),calcitonin gene related peptide(CGRP) were also measured at the end of25week.4.Blood flow test:At the end of25week,after the anesthesia,the rats were infused with acetyleholine and sodium nitroprusside respectively for5minutes thlough the left jugular vein catheter,at the rate of25μg/kg·min.Systolic pressure was recorded through a carotid artery catheter simultaneously.After recording the change in systolie pressure,cut the common carotid artery for electron microscope to observe the ultrastructure of endothelial cells.Test1. Serum lipid levels at baseline in all rats had no significant differences (P>0.05). Serum levels of TC, TG, LDL-C were significantly elevated in high cholesterol diet rats compared with the A group at the end of16week(P<0.05). There was no differences between the high cholesterol groups(P>0.05). Compared with the B and C group, the levels of TC,LDL-C decreassed significantly in D and E group (both P<0.05),and the TC levels were lower in D group than those in E group at the end of25week. In addition, Compared with the B and C group,E group’s rats had decreased TG level significantly(P<0.05),while the TG level in D gourp didn’t decrease significantly(P>0.05). Serum levels of HDL-C in all rats had no significant differences (P>0.05).2. At the end of25week,compared with the A group, the levels of NO increased significantly in the left four groups(P<0.05),and the level of the NO was higher in E group than those in B,C,D groups(P<0.05).Compared with the B and C group, MDA,ET-1levels decreased in D, E groups (P<0.05),well the CGRP and6-keto-PGF1α levels increassed significantly (P<0.05).The TXB2levels was lower in D,E group than those in C group(P<0.05). Serum levels of SOD in all rats had no significant differences (P>0.05).3.At the end of25week, the descending blood pressure extent after infusing SNP comparing those after infusing Ach were signifitantly higher in B and C group(P<0.05),while the left groups had no significant differences (P>0.05).4. In A group we can observe the clear ultrastructure, filling vascular cavity, and flat, smooth and complete endothelial cells with thin basement membrane with electron microscop,while in B group we can observed a lack of continuity between endothelial cells, unclear connective tissues in subendothelial layer, thickened internal elastic lamina, and disorders of elastic fibers. Ultrastructural results of cells in C group showed the most severe changes with swollen endothelial cells, suggesting the initiation of cell death program. Damages of cells in D group were slighter than those in C group. Swollen endothelial cells, disorders and thickening of basement membrane, and unclear boundaries between endothelial cells were observed. Damages of cells in E group were slighter than those in C and D group. Swollen, but not very severe, endothelial cells were observed microscopically, no lipid droplet was found in cytoplasm, and no trafficking of smooth muscle cells was found in intima.Conclusion1. QSYQ drop pills and fluvastatin can adjust dislipidemia, and reduce lipotoxicity on vascular endothelial cells. They also prevent damages of hyper-lipidemia on EC/NO S/NO pathway, and improve the vascular endothelium dependent diastolic dysfunction. It may be better to adjust dislipidemia by using QSYQ drop pills and fluvastatin together.2. QSYQ drop pills and fluvastatin can restrain oxidative stress reaction which may produce too much reactive oxygen species, and recover the activity of eNOS, promote the synthesis and release of NO.It also can decrease oxidation of lipid and NO, then improve nitric oxide bioavailability to protect vascular endothelial cells from injury.3. QSYQ drop pills and fluvastatin can reduce the extent of vasoconstrictors’ effect, restrain platelet aggregation, prevent formation of thrombus, and then protect and repair secretion function of endothelial cells.4. Results of electron microscope show that:after suffered from damages of mechanical and chemical factors, QSYQ drop pills can promote repair of vascular endothelial cells and protect vascular endothelial function.