摘要
目的建立放射性心脏纤维化大鼠模型,观察重组人血管内皮抑制素(恩度)对心肌纤维化的影响,初探转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)与心肌纤维化的相关性。方法将40只SD大鼠按随机数表法分为4组,每组10只,A组为健康对照组;B组为恩度干预组,恩度(6 mg/kg)腹腔连续注射14 d;C组为单纯照射组,心脏照射25 Gy/5次,连续5 d;D组为照射+恩度干预组,恩度给药方法同B组、心脏照射方法同C组。照射后第1、3个月各麻醉处死5只大鼠。Masson染色评估心肌纤维化情况,Western blot检测心肌TGF-β1、CTGF及胶原蛋白Ⅰ(COL-Ⅰ)型表达。结果照射后1和3个月,B组未见明显的心肌纤维化表现,C组和D组可见胶原纤维分布于心肌细胞间质。照射后1个月,半定量分析结果显示A组的心肌胶原容积分数(CVF)为(5.20±0.75)%,C组(10.12±2.17)%和D组(10.32±1.36)均高于A组(t=4.74、4.93,P<0.01),C组和D组的CVF差异无统计学意义(P>0.05);照射后3个月C组的CVF(13.17±2.67)%仍比A组(5.23±1.32)%高(t=4.49,P<0.01),C组的CVF低于D组(16.92±3.58)%(t=3.19,P<0.05)。照射后1个月,A组TGF-β1的表达量为0.441±0.063,C组0.817±0.079高于A组(t=5.81,P<0.01);照射后3个月,A组TGF-β1的表达量为0.501±0.110,C组0.832±0.150高于A组(t=4.19,P<0.01),D组1.403±0.133高于C组(t=7.24,P<0.01)。照射后1、3个月,各组间CTGF及COL-I的变化趋势与TGF-β1的变化趋势相似。结论射线可引起心肌纤维化的形成,重组人血管内皮抑制素可能会加重晚期放射纤维化的形成。
Objective To assess the effects of recombinant human endostatin(rh-ES)on radiation-induced myocardial fibrosis.Methods Totally 40 SD rats were randomly divided into 4 groups,including A group as normal control,B group receiving rh-ES with a dosage of 6 mg·kg-1·d-1,in traperitoneal injection,for 14 consecutive days,C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy,D group receiving rh-ES as the same as B group and local heart irradiation as C group.At 1 and 3 months after irradiation,five rats were killed under anesthesia.Mason staining was used to observe myocardial injury and fibrosis.Western blotting was used to detect the expression of TGF-β1,CTGF and COL-I in myocardium.Results Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation,while collagen fibers were distributed in myocardium in groups C and D.One month after irradiation,the result of semi-quantitative analysis showed that the CVF in group A was(5.20±0.75)%,which was significantly lower than that in group C(10.12±2.17)%(t=4.74、4.93,P<0.01)and the CVF in group D(10.32±1.36),and the CVF of group C was similar to that of group D(P<0.01).Three months after irradiation,CVF in group C(13.17±2.67)%was still higher than that in group A(5.23±1.32)%(t=4.49,P<0.01),but lower than that in group D(16.92±3.58)%(t=3.19,P<0.05).One month after irradiation,the expression of TGF-β1 in group A was 0.441±0.063,lower than that in group C(0.817±0.079,t=5.81,P<0.01).Three months after irradiation,the expression of TGF-β1 in group A was 0.501±0.110,lower than that in group C(0.832±0.150,t=4.19,P<0.01),and the expression of TGF-β1 in group D was 1.403±0.133,which was significantly higher than that in group C(t=7.24,P<0.01).Conclusions Radiation can cause the formation of myocardial fibrosis,and recombinant human endostatin may aggravate the formation of late radiation fibrosis.
作者
旷华香
徐世林
欧阳伟炜
赵朝芬
李晓阳
陈霞霞
杨文刚
马筑
卢冰
苏胜发
Kuang Huaxiang;Xu Shilin;Ouyang Weiwei;Zhao Chaofen;Li Xiaoyang;Chen Xiaxia;Yang Wengang;Ma Zhu;Lu Bing;Su Shengfa(Department of Oncology,Affiliated Hospital of Guizhou Medical University,Teaching and Research Section of Oncology,Guizhou Medical University,Department of Oncology,Guizhou Cancer Hospital,Guiyang 550004,China)
出处
《中华放射医学与防护杂志》
CAS
CSCD
北大核心
2020年第5期343-348,共6页
Chinese Journal of Radiological Medicine and Protection
基金
国家自然科学基金(81660507)
贵州省科技支撑计划项目([2018]2755)。
