目的研究结缔组织生长因子(CTGF)在散发升主动脉瘤(AAA)中的表达及意义,初步探讨AAA发病中主动脉壁病理性重塑的机制。方法选择升主动脉瘤术中切除标本18例为AAA组,冠状动脉旁路移植患者术中主动脉标本18例为对照组,HE染色和Masson染色分别检测主动脉壁的一般情况及胶原含量。免疫组化方法检测主动脉壁中CTGF的表达情况并比较其半定量结果,分析CTGF与临床指标的相关性。应用实时PCR的方法检测所有标本中CTGF和胶原Id1、Ⅲd1(I、Ⅲ型胶原)的mRNA表达水平。结果病理结果显示,与对照组标本比较AAA组标本弹力蛋白降解,胶原纤维增生,平滑肌细胞增生及排列紊乱。AAA组免疫组化结果表明CTGF表达明显增加(44%±4%),主要位于中膜及外膜,对照组表达量较少(33%±5%,P〈0.01)。CTGF的mRNA表达与免疫组化结果一致(P〈0.01)。AAA中胶原10【1、Ⅲ仅1的mRNA水平较对照组高表达(相对表达比值分别为10.54/3.80和1.79/1.19,P〈0.01)。相关性分析结果显示CTGF免疫组化半定量结果与胶原纤维半定量结果及主动脉瘤径均呈正相关(r=0.784,P〈0.01;r=0.793,P〈0.01)。结论CTGF在AAA主动脉壁中表达明显增强,I、Ⅲ型胶原在AAA中表达增加。CTGF表达与主动脉直径大小密切相关。AAA的发病机制涉及主动脉壁的病理性重塑过程,在各种因子作用下主动脉壁胶原代偿性增加。CTGF可能参与其中并发挥了重要作用。
Objective To study the expression of connective tissue growth factor (CTGF) and its significance in sporadic ascending thoracic aortic aneurysm (AAA), and initially to investigate the mechanisms of pathological remodeling in AAA. Methods AAA specimens were taken from 18 patients during elective surgical intervention, and 18 control specimens of ascending aorta were obtained from patients undergoing coronary artery bypass surgery. Specimens were stained with HE and Masson to evaluate the arrangement and aggregation of cells and collagen types I and Ⅲ; immunohistochemistry staining was performed using antibodies directed against markers of CTGF; real-time PCR analysis was performed to quantify the expression level of CTGF and collagen types I and Ⅲ. Results Pathological results show degradation of elastin and hyperplasia of collagen fibers as well as disordered arrangement of smooth muscle cells in AAA. When compared with controls, protein levels of CTGF were significantly increased [ (44± 4 ) % vs. ( 33± 5 ) %, P 〈 0.01 ]. Similar patterns were shown in mRNA levels of CTGF ( P 〈 0. 01 ). Using real-time PCR method, elevated levels ( relative expression ratio of mRNA : 10. 54/3. 8 and 1.79/1.19, respectively; P 〈 0.01, both) of collagen types I and Ⅲ were observed. CTGF expression had a correlation with both collagen fibers and aortic aneurysm diameter ( r = 0. 784, P 〈 0. 01 ; r = O. 793, P 〈 0.01). Conclusions These results indicate increased expression of aortic collagen types I and Ⅲ as well as CTGF in AAA specimens, which is likely to be responsible for the aortic wall pathological remodeling. The expression of CTGF was positively correlated with the aortic diameter. As a cytokines factorcan stimulate collagen synthesis, CTGF may be involved in the pathogenesis and progression of AAA.