CAJ | 학술논문

背景:慢性排斥反应限制了心脏移植患者的长期存活,有报道结缔组织生长因子因其与细胞增殖和胶原合成有关,似乎参与了此过程.目的:假设结缔组织生长因子在大鼠心脏移植慢性排斥反应中发挥作用,实验拟验证其表达与心脏慢性排斥反应病理过程的关系.设计、时间及地点:随机对照动物实验,于2007-04/08在中南大学湘雅二医院动物实?中心完成.材料:取20只Wistar大鼠作为供体,20只SD大鼠作为受体,制作腹部异位心脏移植模型20例次;另选择10只Wistar大鼠作为对照.方法:大鼠腹部异位心脏移植术后,给予环孢素A、霉酚酸酯和甲泼尼龙三联免疫抑制治疗.移植后2,8周分别按随机数字表法麻醉后处死10只受体人鼠,取心脏;10只Wistar大鼠心脏作为对照.主要观察指标:采用苏木精-伊红染色及VanGieson染色观察心肌病珲形态、心肌血管密度及心脏血管狭窄程度;并进行心肌纤维化半定量评分.采用免疫组织化学法检测心肌组织结缔组织生长因子蛋白的表达;并分析结缔组织生长因子表达与慢性排斥反应过程中心肌血管病变及纤维化的相关性.结果:①术后8周移植心脏血管狭窄程度、心肌纤维化评分及结缔组织生长因子蛋白表达量明显高于术后2周及正常心脏(P<0.05～0.01);术后8周移植心脏血管密度低于正常心脏(P<0.05);结缔组织生长因子在正常心脏基本没有表达.②心肌组织结缔组织生长因子蛋白表达灰度值与心肌纤维化、血管狭窄程度均呈负相关(r=-0.734,-0.713,P<0.01),表明结缔组织生长因子表达与心肌纤维化及血管狭窄程度呈正相关.结论:结缔组织生长因子在有心肌血管病变的移植心脏心肌组织中表达增强,其表达与心肌纤维化和心肌血管病变形成有关,在心肌移植排斥反应的病理过程中起重要作用.
배경:만성배척반응한제료심장이식환자적장기존활,유보도결체조직생장인자인기여세포증식화효원합성유관,사호삼여료차과정.목적:가설결체조직생장인자재대서심장이식만성배척반응중발휘작용,실험의험증기표체여심장만성배척반응병리과정적관계.설계、시간급지점:수궤대조동물실험,우2007-04/08재중남대학상아이의원동물실?중심완성.재료:취20지Wistar대서작위공체,20지SD대서작위수체,제작복부이위심장이식모형20례차;령선택10지Wistar대서작위대조.방법:대서복부이위심장이식술후,급여배포소A、매분산지화갑발니룡삼련면역억제치료.이식후2,8주분별안수궤수자표법마취후처사10지수체인서,취심장;10지Wistar대서심장작위대조.주요관찰지표:채용소목정-이홍염색급VanGieson염색관찰심기병혼형태、심기혈관밀도급심장혈관협착정도;병진행심기섬유화반정량평분.채용면역조직화학법검측심기조직결체조직생장인자단백적표체;병분석결체조직생장인자표체여만성배척반응과정중심기혈관병변급섬유화적상관성.결과:①술후8주이식심장혈관협착정도、심기섬유화평분급결체조직생장인자단백표체량명현고우술후2주급정상심장(P<0.05～0.01);술후8주이식심장혈관밀도저우정상심장(P<0.05);결체조직생장인자재정상심장기본몰유표체.②심기조직결체조직생장인자단백표체회도치여심기섬유화、혈관협착정도균정부상관(r=-0.734,-0.713,P<0.01),표명결체조직생장인자표체여심기섬유화급혈관협착정도정정상관.결론:결체조직생장인자재유심기혈관병변적이식심장심기조직중표체증강,기표체여심기섬유화화심기혈관병변형성유관,재심기이식배척반응적병리과정중기중요작용.
BACKGROUND: Chronic rejection limits the long-term success of cardiac transplantation and the underlying causes of the disease are unknown. Connective tissue growth factor (CTGF) is considered as a mitogenic and chemotactic factor for fibroblasts and is associated with cell proliferation and collagen synthesis.OBJECTIVE: To evaluate the role and significance of expression of CTGF in rat chronic rejection heart aliografta.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Laboratory Animal Center of the Second Xiangya Hospital between April and August 2007.MATERIALS: Twenty Wistar rats serving as donors and twenty Sprague-Dawely (SD) rats serving as recipients were included. An additional 10 Wistar rats were included as controls.METHODS: After intra-abdominal heterotopic heart transplantations, rats received cyclosporine A, mycophenolate, and methylprednisolone immunosuppression. Ten recipient rats were anesthetized and sacrificed for heart harvesting at 2 and 8 weeks postoperation, respectively.MAIN OUTCOME MEASURES: Coronary vessel density, fibrosis grade, and intimal occlusion were observed by hematoxylin-cosin staining and Van Gieson staining. Myocardial fibrosis was semi-quantitatively scored. CTGF expression was detected by immunohistochemistry. The associations between CTGF expression and allograft fibrosis and CAV formation were analyzed.RESULTS: Allografts harvested at 8-week post-surgery showed more obvious coronary intimal proliferation, fibrosis and higher CTGF expression compared with the 2-week allografts and the controls (P < 0.05-0.01 ) while the cardiac artery density was lower than the control group (P < 0.05). However, the control group in our study showed negligible CTGF expression. There were strong negative correlations between the gray value of CTGF protein expression and cardiac fibrosis and coronary intimal occlusion (r = -0.734, -0.713, P < 0.01), demonstrating that CTGF protein expression was positively correlated with cardiac fibrosis and coronary intimal occlusion.CONCLUSION: CTGF is expressed in cardiac myocyte with CAV. The increased expression of CTGF in the cardiac allograft is associated with CAV development and fibrosis formation and is involved in the pathogenesis of cbronic heart rejection