摘要
Objective To investigate the effect and underlying mechanism of SULT2B1 in the de-velopment of atherosclerosis(AS).Methods Twelve 8-week-old apolipoprotein E-knockout(apoE-/-)male mice were subjected and fed with a high-fat diet for 12 weeks,and then randomly divided into adeno-associated virus(AAV)-GFP and AAV-shSULT2B1 groups,with 6 animals in each group.In 4 weeks after AAV injection via tail vein,the mice were sacrificed for assessing aortic and aortic root plaque formation by oil red O staining and detecting serum levels of inflam-matory factors and blood lipids.RAW264.7 cells were transfected with adenovirus(Ad)-GFP and Ad-SULT2B1,respectively(n=3).RNA sequencing was performed to detect downstream RNA changes.Then LncRNA gga3-204 was selected for downstream study.After RAW264.7 cells were divided into si-NC group,si-SULT2B1 group,si-Lncgga3-204 group and si-SULT2B1+si-Lncg-ga3-204 group(n=3),and the IL-1β and IL-6 levels were detected in these transfected cells.Results There was no statistically difference in body weight in the mice from the AAV-GFP and AAV-shSULT2B1 groups after high-fat feeding(P＞0.05).Significantly lower serum levels of TC,TG and LDL-C,reduced aortic plaque area[(8.38±1.33)％vs(11.83±1.04)％,P=0.000],and decreased TG content within the aortic root plaque[(12.29±1.54)％vs(17.67±1.53)％,P=0.000]were observed in the AAV-shSULT2B1 group than those in the AAV-GFP group.Ser-um IL-1β and IL-6 levels in the mice of the AAV-shSULT2B1 group than those in the AAV-GFP group(P＜0.01).The AAV-shSULT2B1 group also had obviously lower serum levels of I L-1 βand IL-6 than the AAV-GFP group(P＜0.01).In the RAW264.7 cells from the si-SULT2B1 group,the mRNA levels of IL-1β and IL-6 were notably lower than those in the si-NC group(P＜0.01).LncRNA gga3-204 expression was significantly higher in the Ad-shSULT2B1 group than the Ad-GFP group(P＜0.01).While,the si-SULT2B1 group had statistically higher Lncgga3-204 level than the si-NC group(2.32±0.60 vs 1.19±0.21,P=0.036).The si-Lncgga3-204 group had significantly higher IL-1β and IL-6 mRNA levels than the si-NC group(P＜0.01).The si-SULT2B1+si-Lncgga3-204 group had significantly higher IL-1β and IL-6 mRNA levels than the si-SULT2B1 group(P＜0.05).Conclusion SULT2B1 affects the macrophage inflammatory response via Lncgga3-204,and then affects the progression of AS.