医学论文范文:rAAV2/1Acrp30对动脉粥样硬化的GK大鼠NFκB及黏附分子的影响
【摘要】 目的 观察rAAV2/1Acrp30对动脉粥样硬化GK大鼠模型血清可溶性细胞间黏附分子(sICAM1)、可溶性血管内皮黏附分子(sVCAM1)水平和NFκB表达的影响,从血管炎症的角度探讨脂联素对糖尿病大血管病变的作用。方法 将造模成功的30只动脉粥样硬化的GK大鼠分为三个处理组:①模型1组,后肢肌肉注射盐水;②模型2组,后肢肌肉注射空病毒rAAV2/1;③治疗组,后肢肌肉注射 rAAV2/1Acrp30。治疗8周后处死所有大鼠,比较三组之间血清sICAM1,sVCAM1及主动脉处NFκBp65 mRNA的表达水平。结果 治疗组和模型1组、模型2组比较,血清sVCAM1、sICAM1显著降低(P<0.05)。治疗组和模型1组、模型2组比较,主动脉NFκBp65 mRNA表达显著下调(P<0.05)。结论 rAAV2/1Acrp30可通过抑制NFκB的表达,减轻炎症反应而对糖尿病大血管病变产生保护作用。
【关键词】 脂联素;2型糖尿病大血管病变;核转录因子;可溶性细胞间黏附分子;可溶性血管内皮黏附分子
Effects of rAAV2/1Acrp30 on NFκB and adhesion molecule
in GK rats with atherosclerosisZHONG Huiju1, ZHANG Ying1, LI Qiangxiang2, LI Guo1
(1. Department of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008;
2. Institute of Political Science and Administration, Central South University, Changsha 410083, China)ABSTRACT: Objective To study the effects of rAAV2/1Acrp30 on sICAM1 and sVCAM1 level as well as NFκB expression in GK rats with diabetic arteriosclerosis so as to explore the effect of adiponectin on diabetic macroangiopathy. Methods A total number of 30 atherosclerotic GK rat models were randomly divided into three groups: ① Model group one (M1): hind limb intramuscular injection of normal saline; ② Model group two (M2): hind limb intramuscular injection of vacuity virus rAAV2/1; ③ Treatment group (T): hind limb intramuscular injection of rAAV2/1-Acrp30 at a dose of 1×1012mg/L. After 8 weeks treatment, the rats were killed, and serum sVCAM1 and sICAM1 level as well as aortic NFκBp65mRNA expression were measured in each group. Aortic NFκBp65mRNA expression was measured by RTPCR.Results Compared with those in control model groups (M1 and M2), sVCAM1 and sICAM1 levels were decreased significantly in the treatment (T) group (P<0.05). Aortic NFκBp65 mRNA expression was significantly downregulated in the treatment (T) group compared with that in control model groups (M1 and M2) (P<0.05). Conclusion rAAV2/1Acrp30 may produce protective effects on diabetic atherosclerosis by decreasing inflammatory reactions医.学全.在.线网站www.lindalemus.com.
KEY WORDS: adiponectin; diabetic macroangiopathy; nuclear factorκB (NFκB); soluble intercellular adhesion molecule (sICAM1); soluble vascular cell adhesion molecule (sVCAM1)
炎症发病学说是近年来2型糖尿病病因与发病机制的重大进展。该学说认为:炎症反应在2型糖尿病及大血管病变的发生、发展中具有重要作用。核因子NFκB(nuclear factor)是调控基因转录的重要因子,它可与许多蛋白质基因启动子和增强子部位的κB序列结合,诱导这些蛋白表达增强,从而参与炎症反应及动脉粥样硬化等多种疾病的病理过程。NFκB的活化会极大的刺激炎症因子如血管细胞黏附分子1(vascular cell adhesion molecule1, VCAM1)、细胞间黏附分子1(intracellular adhesion molecule1, ICAM1)、E选择素(Eselectin)等细胞黏附分子的转录与表达。上述细胞因子的增多可趋使单核巨噬细胞、淋巴细胞的侵入和聚集在动脉内膜下,内膜下的细胞活化后可合成及分泌前炎症介质如白介素6、白介素8、肿瘤坏死因子(tumor necrosis factor, TNFα)等[1]。NFκB是动脉粥样硬化前炎症介质、炎症因子和炎症产物的中枢调节者[2]。