肥厚型梗阻性心肌病合并房颤中CTGF的表达及病理学机制

目的 观察结缔组织生长因子（CTGF）在肥厚型梗阻性心肌病（HOCM）合并房颤（AF）心房组织中的表达，探讨HOCM中AF发生的分子学机制 方法 HOCM合并AF患者术中切除左心房标本15例为房颤组，倾向性匹配单纯HOCM患者左心房标本15例为对照组，Masson染色检测两组心房组织的胶原表达。免疫组化方法及Western blot方法检测心房组织中CTGF及mTOR的表达情况及蛋白表水平。实时PCR的方法检测两组标本中CTGF及mTOR的mRNA表达水平 结果 房颤组心房细胞肥大，间质胶原纤维明显增生，且排列紊乱，分布不匀，形成灶性瘢痕，心内膜纤维组织增生；胶原半定量分析结果显示实验组平均光密度高于对照组，差异有统计学意义（P<0.01）。免疫组化结果显示，房颤组CTGF在心房壁各层均有表达，以内膜和中膜肌细胞及成纤维细胞中阳性表达更显著，mTOR蛋白在心房壁中各层均有表达。Western blot结果提示：房颤组CTGF及mTOR的蛋白表达明显高于对照组（P<0.01）。实时PCR结果显示房颤组CTGF及mTOR的RNA表达量上调，差异有统计学意义（P<0.01）。CTGF平均光密度与Masson染色胶原表达量呈正相关（r=0.738，P<0.01）。mTOR的表达与胶原的表达呈正相关（r=0.614，P<0.01）；分析mTOR表达量与CTGF的关系发现二者也存在相关性（r=0.64，P<0.01）。结论 与单纯HOCM患者相比，HOCM合并AF的患者心房组织中胶原纤维化明显，CTGF和mTOR的蛋白含量和mRNA水平是增加的，提示CTGF及其信号通路在HCM合并房颤的发生发展过程中具有重要的作用，可能通过促进胶原的合成参与了AF的发病。

The expression and pathological mechanism of CTGF in hypertrophic obstructive cardiomyopathy with atrial fibrillation

Objective To observe the expression of connective tissue growth factor (CTGF) in atrial tissue of hypertrophic obstructive cardiomyopathy (HOCM) with atrial fibrillation (AF), and to explore the molecular mechanism of AF in HOCM. Methods Fifteen left atrial specimens from patients with HOCM and AF were resected as the experimental group, and 15 left atrial specimens from patients with HOCM alone were used as the control group. Masson staining was used to detect the collagen expression in the atrial tissues of the two groups. The expression of CTGF and mTOR in atrial tissue and the level of protein surface were detected by immunohistochemistry and Western blot. Detection of CTGF and mTOR in two groups by real-time PCR. Results In the experimental group, atrial cells were hypertrophic, interstitial collagen fibers were obviously increased, and arranged disorderly, distributed unevenly, forming focal scars and endocardial fibrous tissue proliferation. Semi-quantitative analysis of collagen showed that the average optical density of the experimental group was higher than that of the control group, and the difference was statistically significant (P < 0.01). Immunohistochemical results showed that CTGF was expressed in all layers of the atrial wall in the experimental group, especially in the intima and medial myocytes and fibroblasts, and mTOR protein was expressed in all layers of the atrial wall. Western blot results showed that the protein expression of CTGF and mTOR in the experimental group was significantly higher than that in the control group (P < 0.01). Real-time PCR results showed that the expression of CTGF and mTOR was up-regulated in the experimental group, and the difference was statistically significant (P < 0.01). The average optical density of CTGF was positively correlated with the expression of collagen in Masson staining (r = 0.738, P < 0.01). The expression of mTOR was positively correlated with the expression of collagen (r = 0.614, P < 0.01), and the relationship between mTOR expression and CTGF was found to be positively correlated (r = 0.64, P < 0.01). Conclusion Compared with patients with HOCM alone, collagen fibrosis in atrial tissue of patients with HOCM and AF was obvious, and the protein and mRNA levels of CTGF and mTOR were increased, suggesting that CTGF and its signaling pathway play an important role in the occurrence and development of HCM with AF, and may participate in the pathogenesis of AF by promoting collagen synthesis.