摘要
目的探讨类抵抗素分子ɑ或炎症区域分子1(RELMɑ/FIZZ1)对载脂蛋白E(ApoE)基因敲除小鼠动脉粥样硬化斑块稳定性及血管新生的影响及其信号通路。方法 8周龄C57BL/6J ApoE基因敲除鼠20只,喂食高脂饲料12周后随机分为模型组及RELMɑ/FIZZ1组,另选10只C57BL/6J野生型小鼠作为对照组;RELMɑ/FIZZ1组于尾部血管注射重组RELMɑ/FIZZ1干预2周后结束实验。取小鼠主动脉制备石蜡包埋切片,进行HE染色,利用图像软件定量测量斑块面积、血管横截面积及校正斑块面积,采用免疫组织化学染色测定主动脉血管壁RELMɑ/FIZZ1及CD34阳性反应强度。提取主动脉RNA,采用全基因表达谱筛选出显著表达差异的基因和发生变化的细胞通路。结果与对照组相比,模型组动脉粥样硬化明显,斑块面积增加,粥样硬化斑块内RELMɑ/FIZZ1表达明显。RELMɑ/FIZZ1刺激后RELMɑ/FIZZ1及CD34阳性反应强度增强,校正斑块面积比模型组显著性增加(31.58%±6.65%比24.16%±3.59%,P<0.01),明显刺激血管新生(P<0.05)。相对于对照组,RELMɑ/FIZZ1组有显著性上调基因391个,下调基因465个;活性显著性上调信号通路12条,活性显著性下调信号通路10条,共计22条。结论 RELMɑ/FIZZ1刺激血管新生,造成粥样斑块不稳定,其机制与Atg9a、Gng8等基因显著性表达及细胞肌动蛋白骨架调节通路、缝隙连接信号通路的激活密切相关。
Aim To investigate the RELMɑ/FIZZ1 signal pathway in intervening atherosclerosis in experimental animals,and inspect its influences on angiogenesis. Methods 20 ApoE-/-mouse were fed with high fat diet for 12 weeks and randomly divided into 2 groups equally. The model group were fed with high fat diet and another group were fed with high-fat diet but were injected with RELMɑ /FIZZ1 for 2 weeks. 10 C57 BL /6J mice were fed with normal diet for control; The positive area of plaque were determined. The RELMɑ /FIZZ1 and CD34 positive response intensity at aorta vessel wall,and the capillary density in plaque were measured by immunohistochemical staining. Investigate the abnormally expressed genes and changed signal pathway via array hybridization. Results Compared to control group,model group atherosclerosis plaque formed in mouse arteriae. RELMɑ /FIZZ1 protein had obvious expression by immunohistochemistry in atherosclerotic plaque. Compared to model group,the correcting plaque area was significantly increased in RELMɑ /FIZZ1group（31. 58% ± 6. 65% vs 24. 16% ± 3. 59%,P 〈 0. 01）. The RELMɑ /FIZZ1 and CD34 positive response intensity and the capillary density in RELMɑ /FIZZ1 group were higher than those in model group（P 〈 0. 01）. Array hybridization data analysis shows that 856 genes expressed difference significantly,which 391 genes raised while 465 genes lowered,and 22 signaling pathways are significantly different,including that 12 signaling pathways are activity raised while 10 signaling pathways are activity down. Conclusions RELMɑ /FIZZ1 could promote the progression of atherosclerosis plaque by stimulating angiogenesis. The mechanism has a close relationship with the significant expression of Atg9 a and Gng8 genes,the regulation of actin cytoskeleton pathway（rno04810） and the activation of gap junction（rno04540） cell.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2014年第9期902-906,共5页
Chinese Journal of Arteriosclerosis
基金
贵州省科技攻关项目(黔科合SY[2010]3081号)
