高脂血症对大鼠主动脉壁连接蛋白mRNA表达的影响

目的通过观察高脂血症对大鼠血管壁连接蛋白(connexin,Cx)37、40、43及45 mRNA表达的影响,探讨AS的发病机制.方法雄性Wistar大鼠72只,按体重随机分为3组.分别给予基础饲料(C组)、嘧啶胆酸钠饲料(P组)及高脂饲料(HF组)喂养.于实验开始前1 d给予P组及HF组大鼠Vit D360万U/kg 1次性腹腔内注射,此后每30 d追加Vit D330万U/kg.C组大鼠给予等体积生理盐水腹腔内注射.各组大鼠于实验8周及22周分两批处死.心脏穿刺取血测定血清胆固醇(CH)及甘油三酯(TG).然后取胸主动脉行病理检查;取腹主动脉匀浆后提取总RNA,利用RT-PCR分析腹主动脉Cx mRNA的表达水平.结果在实验8周及22周时HF组大鼠血清CH[(10.50±5.21)mmol/L及(10.98±1.87)mmol/L]和TG[(7.25±1.98)mmol/L及(7.52±1.69)mmol/L]水平明显高于其余两组.HF组大鼠在实验8周时主动脉内膜面可见较多散在斑点状红色脂质浸润区,内皮细胞及平滑肌细胞增生.实验22周时可见粥样斑块形成及管壁钙化.实验8周时半定量Cx 43 mRNA水平(0.91±0.30)明显高于其余两组,实验22周时各组间Cx 43 mRNA水平无统计学差异.其余三种连接蛋白(Cx 37、Cx 40、Cx 45)mRNA水平在实验8周和22周时各组间均未见统计学差异.结论血管壁表达的四种主要Cx中,Cx 43受高脂血症影响表达量增加;Cx 37、Cx 40及Cx 45 mRNA表达量则不受上述因素的影响.

The effects of hyperlipidemia on the expressions of connexin 37, 40, 43, 45 messenger RNA in the rat aortal wall

Objective To observe the effects of hyperlipidemia on the expressions of connexin 37,40,43,45 messenger RNA in aortal walls of rats and to investigate the mechanism of atherosclerosis.MethodsSeventy two male,Wistar rats were subjected to the following regimens respectively:(1) normal chow saline(ip) for 8 or 22 weeks(group C);(2) Propylthiouracil and cholic acid chow VitD3(ip) for 8 or 22 weeks(group P);(3) high lipid chow VitD3(ip) for 8 or 22 weeks(group HF).Biochemical,histological,immunohistochemical techniques and RT-PCR were used.The levels of serum CH,TG were assessed.The gross and histological lesion of aortal walls were observed.The gene expression profiles of Connexin(Cx)37,Cx 40,Cx 43 and Cx 45 in aortic walls were analyzed.ResultsIn group HF,at the 8th and 22th week,the concentrations of serum CH and TG increased significantly compared with those of the group C and group P.At the 8th week,the intina of whole aortal wall showed red stained lipid lesion,embeded with vessel endothelial cells and the smooth muscles cells.At the 22th week,atheroma and calcification were present.The expression level of Cx 43 mRNA of the abdominal aorta in group HF was much higher than that in other two groups at 8th week.The expression levels of Cx 37,Cx 40,and Cx 45 mRNA of the abdominal aorta had no significant difference among all 3 groups at the 22thand 8th weeks.ConclusionsChronic hyperlipidemia up-regulate the expressions of Cx 43 gene in the abdominal aortic wall.The mRNA expressions of Cx 37,Cx 40 and Cx 45 in the rat abdominal aorta are not influenced by hyperlipidemia.