醫(yī)學(xué)論文范文:rAAV2/1Acrp30對動脈粥樣硬化的GK大鼠NFκB及黏附分子的影響
【摘要】 目的 觀察rAAV2/1Acrp30對動脈粥樣硬化GK大鼠模型血清可溶性細(xì)胞間黏附分子(sICAM1)、可溶性血管內(nèi)皮黏附分子(sVCAM1)水平和NFκB表達(dá)的影響,從血管炎癥的角度探討脂聯(lián)素對糖尿病大血管病變的作用。方法 將造模成功的30只動脈粥樣硬化的GK大鼠分為三個處理組:①模型1組,后肢肌肉注射鹽水;②模型2組,后肢肌肉注射空病毒rAAV2/1;③治療組,后肢肌肉注射 rAAV2/1Acrp30。治療8周后處死所有大鼠,比較三組之間血清sICAM1,sVCAM1及主動脈處NFκBp65 mRNA的表達(dá)水平。結(jié)果 治療組和模型1組、模型2組比較,血清sVCAM1、sICAM1顯著降低(P<0.05)。治療組和模型1組、模型2組比較,主動脈NFκBp65 mRNA表達(dá)顯著下調(diào)(P<0.05)。結(jié)論 rAAV2/1Acrp30可通過抑制NFκB的表達(dá),減輕炎癥反應(yīng)而對糖尿病大血管病變產(chǎn)生保護(hù)作用。
【關(guān)鍵詞】 脂聯(lián)素;2型糖尿病大血管病變;核轉(zhuǎn)錄因子;可溶性細(xì)胞間黏附分子;可溶性血管內(nèi)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醫(yī).學(xué)全.在.線網(wǎng)站m.f1411.cn.
KEY WORDS: adiponectin; diabetic macroangiopathy; nuclear factorκB (NFκB); soluble intercellular adhesion molecule (sICAM1); soluble vascular cell adhesion molecule (sVCAM1)
炎癥發(fā)病學(xué)說是近年來2型糖尿病病因與發(fā)病機(jī)制的重大進(jìn)展。該學(xué)說認(rèn)為:炎癥反應(yīng)在2型糖尿病及大血管病變的發(fā)生、發(fā)展中具有重要作用。核因子NFκB(nuclear factor)是調(diào)控基因轉(zhuǎn)錄的重要因子,它可與許多蛋白質(zhì)基因啟動子和增強(qiáng)子部位的κB序列結(jié)合,誘導(dǎo)這些蛋白表達(dá)增強(qiáng),從而參與炎癥反應(yīng)及動脈粥樣硬化等多種疾病的病理過程。NFκB的活化會極大的刺激炎癥因子如血管細(xì)胞黏附分子1(vascular cell adhesion molecule1, VCAM1)、細(xì)胞間黏附分子1(intracellular adhesion molecule1, ICAM1)、E選擇素(Eselectin)等細(xì)胞黏附分子的轉(zhuǎn)錄與表達(dá)。上述細(xì)胞因子的增多可趨使單核巨噬細(xì)胞、淋巴細(xì)胞的侵入和聚集在動脈內(nèi)膜下,內(nèi)膜下的細(xì)胞活化后可合成及分泌前炎癥介質(zhì)如白介素6、白介素8、腫瘤壞死因子(tumor necrosis factor, TNFα)等[1]。NFκB是動脈粥樣硬化前炎癥介質(zhì)、炎癥因子和炎癥產(chǎn)物的中樞調(diào)節(jié)者[2]。