| As one of the most popular beverages in the world,black tea has proven to have a variety of beneficial health effects to the human body,including antioxidant effect,anti-inflammatory effect,weight loss and lipid-lowering effect.Cardiovascular disease(CVD)is a chronic non-communicable disease that seriously threatens the life and health of residents.At present,about 290 million people in China suffer from CVD,and the number of deaths caused by CVD accounts for the top of the total number of deaths caused by the disease.Its occurrence and development are closely related to dietary factors.The relationship between black tea consumption and CVD has attracted much attention,but up to now,epidemiological studies on the relationship between black tea consumption and CVD incidence have not been consistent.Whether black tea has cardiovascular protective effect is not clear,and the underlying molecular mechanism is still unclear.Atherosclerosis(AS)is the key common pathological cause of CVD,and vascular endothelial cell injury is the early key link of AS.Therefore,protecting vascular endothelial cells from injury is an important strategy to prevent AS and CVD.In this study,human umbilical vein endothelial cells(HUVECs)were cultured in vitro,cell damage was induced by high concentration of cholesterol,and the occurrence and development of AS in ApoE-/-mice were induced by high fat diet,and an experimental model was established in vivo.To observe and evaluate the protective effect of theaflavins(TF),the main bioactive component in black tea,on endothelial cell injury and the inhibitory effect on the occurrence and development of AS in vivo.At the same time,the relevant mechanism of action was further explored to reveal the potential cardiovascular protective effect of black tea and its molecular mechanism.The main research results are as follows:(1)In experiment 1,in the concentration range of 0-100 ?mol/L,theaflavins had no obvious toxic effect on HUVECs.The HUVECs were stimulated with 10 ?mol/L cholesterol for 24 h to establish the injury model of cells in vitro. Compared with model group,cell viability and NO secretion in theaflavins pretreated groups(5 and 10 ?mol/L)were significantly increased(P<0.05),while cell apoptosis rate and LDH release were significantly decreased(P<0.05).In addition,intracellular ROS and MDA contents were significantly decreased(P<0.05).These results indicate that a certain dose of theaflavins pretreatment could effectively reduce the oxidative stress injury of vascular endothelial cells induced high cholesterol concentration.(2)In experiment 2,ApoE-/-mice were fed with a high fat diet for 12 weeks,and an in vivo model of AS was established.Compared with the high-fat group,the body weight of mice in theaflavins low-dose and high-dose groups(5 and 10 mg/kg·d)was decreased,but there was no significant difference(P>0.05).The serum TC and LDL-C levels in theaflavins low-dose and high-dose group were significantly decreased(P<0.05),while the serum TG level in theaflavins high-dose group was significantly decreased,while the serum HDL-C level was significantly increased(P<0.05).The pathological section of mouse aorta showed that compared with the high-fat group,the aorta wall intima of mice in theaflavins low-dose and high-dose group were significantly thinner,the foam cell aggregation and lipid deposition were improved,the plaque area was significantly reduced(P<0.05),and collagen was formed.At the same time,the contents of ROS and MDA in aorta were significantly decreased(P<0.05).In addition,the m RNA level of MMP-2/9 in aorta of mice in theaflavins low-dose and high-dose groups was significantly decreased(P<0.05),the protein expression level of MMP-2 in aorta of mice in theaflavins low-dose and high-dose theaflavins groups was significantly decreased(P<0.05).These results indicate that a certain dose of theaflavins dietary intervention could effectively reduce the pathological progression of AS in ApoE-/-mice induced by high-fat diet.(3)In experiment 3,theaflavins treatment could increase the activities of SOD,CAT and GSH-Px in cells and mouse aorta to different degrees.Western blot analysis showed that theafavins could effectively up-regulate the expression of Nrf2 and HO-1 proteins,and activate the Nrf2/HO-1 signaling pathway.In addition,the addition of Nrf2 inhibitor ML385 significantly decreased the cell viability and the expression levels of Nrf2 and HO-1 proteins in theaflavins pretreated group(10 ?mol/L),and increased the apoptosis rate.These results suggest that theaflavins could activate the Nrf2 /HO-1 pathway to play a protective role against vascular endothelial injury.In conclusion,teaflavins could effectively reduce vascular endothelial cells from oxidative stress injury and the pathological progression of AS induced by high fat,and it was believed that the protective effect is mainly realized through activation of Nrf2/HO-1 signaling pathway. |
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