摘要
目的探讨多柔比星(Dox)介导的血管损伤在促进主动脉夹层(AD)发生发展中的作用机制。方法选取武汉大学人民医院行胸AD全弓置换患者10例为实验组,同期选择心脏移植术患者3例为对照组,2组均于术中取AD血管标本。另取3周龄雄性C57BL/6J野生型小鼠18只,随机分为3组,每组6只,对照组(WT组)、β氨基丙腈酯(BAPN)组(第3周开始饲喂含0.25%BAPN小鼠维持饲料)、BAPN+Dox组(根据体质量每周腹腔注射3mg/kg Dox,连续5周,第3周开始饲喂饲料同BAPN组),5周后,游离小鼠主动脉,4%多聚甲醛固定,石蜡包埋,切片。免疫组织化学及Western blot检测组织P53蛋白表达,TUNEL染色检测细胞凋亡情况。结果实验组P53蛋白较对照组明显升高(0.76±0.05 vs 0.39±0.11),凋亡细胞明显增多[(38.3±8.7)%vs (12.6±1.2)%](P<0.01)。BAPN+Dox组死亡率明显高于BAPN组(100.0%vs 66.7%);BAPN+Dox组组织P53蛋白较BAPN组显著升高;VSMC凋亡明显增多,且2组P53蛋白和血管平滑肌细胞(VSMC)凋亡均较WT组明显升高(P<0.01)。结论 Dox介导的血管损伤可能通过诱导VSMC凋亡,促进AD发生发展。
Objective To study the mechanism of doxorubicin-mediated vascular injury in promoting the progression of aortic dissection(AD).Methods Ten patients who underwent thoracic AD replacement served as an experimental group and 3 patients who underwent heart transplantation in our hospital served as a control group.AD tissue sampls were taken during the operation.In addition,18 C57BL/6J wild mice aged 3 weeks were divided into control group(n=6),BAPN group(n=6)and BAPN+doxorubicin group(n=6).After the animals in BAPN group were fed on a forage containing 25%BAPN and those in BAPN+doxorubicin group received intraperitoneal injection of doxorubicin for 5 weeks,AD tissue samples were fixed with 4%paraformaldehyde,embedded in paraffin,and cut into sections.Expression of P53 protein in AD tissue samples was detected by Western blot with immunohistochemical staining.Apoptosis of VSMC was detected with TUNEL staining.Results The expression level of P53 protein and apoptotic rate of VSMC were significantly higher in experimental group than in control group(P<0.01).The mortality was significantly higher in BAPN+doxorubicin group than in BAPN group(100.0%vs 66.7%,P<0.01).The expression level of P53 protein and apoptotic rate were significantly higher in BAPN+doxorubicin group than in BAPN group(P<0.01).Conclusion Doxorubicin-mediated vascular injury can promote the progression of AD by inducing the apoptosis of VSMC.
作者
吴琪
王志维
Wu Qi;Wang Zhiwei(Department of Cardiothoracic Surgery,Wuhan University People'sHospital,Wuhan 430060,Hubei Province,China)
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2019年第4期421-425,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(8157020938)
