摘要
目的:探讨核转录因子(NF)-κB抑制剂二硫代氨基甲酸吡咯烷(PDTC)对小鼠急性心肌梗塞(AMI)后Wnt信号通路的影响。方法:结扎3月龄雄性C57/BL小鼠左冠状动脉建立AMI模型,随机分成AMI+PDTC组(36只,术后每日腹腔注射PDTC120mg/kg),AMI组(36只,每日注射同上述剂量的生理盐水)。所有小鼠按心梗时间分3d、7d、14d亚组,比较应用PDTC后NF-κB信号通道相关的p65,Wnt信号通路的Dishellved(dvl)-1mRNA表达,糖原合成激酶(GSK)-3β总水平及磷酸化水平变化,β-连接蛋白(catenin)及缝隙通道连接蛋白(connexin)43表达。结果:与AMI组相比,AMI+PDTC组的p65,dvl-1mRNA表达显著降低(P均<0.05),p/tGSK-3β3d,7d及14d时均显著升高(P值均为0.000);β-catenin表达3d时显著低于AMI组,7d时显著高于AMI组(P值均为0.000);connexin43表达显著降低(P=0.000)。结论:抑制NF-κB活性、信号通道后Wnt信号通路相关蛋白活性也发生变化,说明急性心肌梗塞后NF-κB信号通路与Wnt信号通路之间存在互通作用。
Objective： To study the effects of NF-κB inhibitor -PDTC on expression of protein related to Wnt signal pathway in mice post-infarction. Methods： Choose 3 months C57/BL mice to set up acute myocardial infarction animal model by ligation of left coronary artery . They were divided to AMI＋PDTC group （36 cases, mice was treated with injected PDTC on dose of 120 mg/kg · d） and AMI group （36 cases, mice was treated with injected physiological saline with same volume） . They were divided into 3 subgroups according to time post-infarction： ad, 7d, 14d post infarction and detected expression of p65 related to NF-κB signal pathway by immunohistochemistry; and protein related to Wnt signal pathway： dvl-1 mRNA by RT PCR, total （t） and phosphorylation （p） level of glucogen synthesis kinase （GSK） -3β, β-catenin, connexin 43 by Western-blot in left ventricular. Results： Expression of p65 decreased in AMI＋PDTC group （P〈0.05）. Compared with AMI group expression of dvl-1 mRNA decreased in AMI ＋PDTC group （P〈0.05）. While ratio of p/t- GSK-3β was higher in AMI＋PDTC group on 3d, 7d and 14d postinfarction than it in AMI group （P= 0. 000 all）. Expression of β-catenin was lower on 3d post-infarction, and in- creased on 7d postinfarction （P=0. 000） in AMI＋PDTC group. Expression of eonnexin 43 was much lower in AMI ＋PDTC group compared with AMI group （P=0. 000）. Conclusion： Expression of protein related to Wnt signal pathway also altered after used NF-κB inhibitor -PDTC. That means ＂crosstalk＂ existed between Wnt and NF-κB signal pathway postinfarction.
出处
《心血管康复医学杂志》
CAS
2010年第3期230-234,F0003,共6页
Chinese Journal of Cardiovascular Rehabilitation Medicine
基金
国家自然科学基金项目(30760263)
新疆维吾尔自治区重点实验室项目(XJDX0903)
