摘要目的 观察受体转谷氨酰胺酶(TG2)和Mer受体酪氨酸激酶(Mertk)共沉默的腺病毒干扰载体在小鼠动脉粥样硬化(AS)斑块失稳中的作用.方法 建立小鼠AS模型,随机分为pAdTrack/TG2/Mertk组(n=10)、pAdTrack/TG2组(n=10)以及pAdTrack/Mertk组(n=10),于一侧髂总动脉斑块局部分别转染上述腺病毒干扰载体,另一侧髂总动脉转染pAdTrack/绿色荧光蛋白(GFP)作为对照组.转染8周后,采用Western blot法检测各组斑块内TG2和Mertk蛋白表达,采用显微超声检测斑块的偏心指数和重构指数,并计算易损指数,采用免疫组织化学法检测斑块的脂质、胶原、巨噬细胞和平滑肌细胞含量.结果 pAdTrack/TG2/Mertk组和pAdTrack/TG2组的TG2蛋白表达差异无统计学意义(P＞0.05),但两组均显著低于pAdTrack/Mertk组和pAdTrack/GFP组的TG2蛋白表达(P＜0.01),pAdTrack/TG2/Mertk组和pAdTrack/Mertk组的Mertk蛋白表达比较差异无统计学意义(P＞0.05),但两组均显著低于pAdTrack/TG2组和pAdTrack/GFP组的Mertk蛋白表达(P＜0.01);与其他3组比较,pAdTrack/TG2/Mertk组的偏心指数和重构指数显著增高(P＜0.05),pAdTrack/TG2/Mertk组易损指数显著增高(P＜0.01),pAdTrack/TG2/Mertk组脂质含量显著增高(P＜0.01),pAdTrack/TG2/Mertk组胶原含量显著降低(P＜0.05),pAdTrack/TG2/Mertk组巨噬细胞含量显著增高(P＜0.05),而每组的平滑肌数量差异无统计学意义(P＞0.05).结论 TG2和Mertk共沉默的腺病毒干扰载体在小鼠AS斑块失稳中起着重要作用.

abstractsObjective To evaluate the role of adenovirus vector plasmid targeting both transglutaminase 2 (TG2) and Mer receptor tyrosine kinase (Mertk) in mouse atherosclerotic plaque losing stability.Methods Mouse atherosclerosis (AS) model was established.Thirty mice were divided randomly into pAdTrack/TG2/Mertk group (n =10),pAdTrack/TG2 group (n =10),and pAdTrack/TG2 group (n =10).One side of common iliac artery of each group was transfected locally with corresponding pAdTrack/TG2/Mertk,pAdTrack/TG2 or pAdTrack/TG2.Other side of common iliac artery was transfected locally with pAdTrac/GFP as control group.After 8 weeks,the protein expression of TG2 and Mertk was detected by using Western blotting.Eccentric index (EI) and remodeling index (RI) were calculated by micro-ultrasound measurement,and vulnerable index was calculated.Lipid,collagen,macrophage and smooth muscle cell positive area of AS plaque in each group were examined by using immunohistochemistry.Resuits Compared with pAdTrack/Mertk group and control group,the expression level of TG2 in the AS plaque of pAdTrack/TG2/Mertk group and pAdTrack/TG2 group was decreased obviously (P ＜ 0.01),but there was no significant difference between later two groups.Compared with pAd/TG2 group and control group,the expression level of Mertk in the AS plaque of pAdTrack/TG2/Mertk group and pAdTrack/Mertk group was decreased obviously (P ＜ 0.01),but there was no significant difference between later two groups.Compared with other 3 groups,EI and RI in pAdTrack/TG2/Mertk group was increased obviously (P ＜ 0.05),vulnerable index increased obviously (P ＜ 0.01),lipid increased obviously (P ＜ 0.01),collagen decreased obviously (P ＜ 0.05),and macrophage increased obviously (P ＜ 0.05),but smooth muscle cells showed no significant difference among groups (P ＞ 0.05).Conclusion The adenovirus vector plasmid targeting both TG2 and Mertk plays an important role in mouse atherosclerotic plaque losing stability.