摘要
目的观察移植物动脉血管病（TA）的内膜病变机制和反义细胞外信号调节激酶2基因腺病毒载体（Adanti．ERK2）基因治疗的效果。方法建立Brown．Norway（BN）-Lewis移植物动脉血管病模型，分为同系组、Control组、LacZ组和Adanti—ERK2组（给予5×10^9pfuAdanti—ERK2基因治疗），每组各6例。术后60d检测各组内膜病变和血管腔内膜／（内膜＋中膜）比，α-肌动蛋白（d—actin）和血小板源性生长因子．BB（PDGF—BB）染色检测移植动脉平滑肌细胞（VSMCs）增殖和分泌功能，评估移植动脉新生毛细血管情况并检测移植动脉中环氧化酶．2（COX-2）的表达。结果术后60d同系组内膜无异常，Control组和LaeZ组典型内膜增殖改变，Adanti—ERK2组内膜病变较轻；内膜／（内膜＋中膜）比各组分别为7．6％、81．4％、85．9％、15．9％；α-actin阳性细胞（内膜平滑肌细胞）每视野计数各组分别为0、71．3±9．2、76．4±11．3、34．8±5．3；PDGF—BB阳性细胞每视野计数各组分别为0．9±0．5、28．4±3．4、29．1±3．2、8．6±1．7；移植动脉中膜和内膜新生毛细血管检测各组分别无、丰富、丰富、少量；COX．2新生血管阳性细胞计数各组分别为0、36．3±8．3、40．9±9．2、10．4±3．9。Adanti．ERK2组与其他组别间比较，差异有统计学意义（P〈0．05）。结论内膜增生，血管腔缩窄，PDGF．BB诱导内膜平滑肌细胞募集分化并激发血管新生是TA重要病理生理环节，Adanti—ERK2基因治疗可有效干预各发病环节，达到治疗效果。
Objective To explore the mechanisms of intimal injury underlying transplant arterio- sclerosis （TA） and to clarify the treatment effect of adenovirus-mediated anti-extracellular signal regulated kinase 2 （Adanti-ERK2） gene therapy on TA. Methods The Brown-Norway （BN）-Lewis TA model was employed. According to different gene therapy, the recipients were divided into isograft group, control group, LacZ group, which were used as control, and Adanti-ERK2 group （5 ×10^9 pfu Adanti-ERK2 was transferred into the graft before transplant, 6 cases in each group）. The grafts were harvested on the day 60 post-transplantation to evaluate the intimal injury and calculate the ratio of intima/（ intima ＋ media）. The staining of ct-actin and PDGF-BB was performed to analyze proliferation and secretion of vascular smooth muscle cells （VSMCs）. The angiogenesis was evaluated and the cyclooxygenaseo2 （COX-2） staining was detected. Results The intima was normal in the isograft group but a typical intimal proliferation was ob- served in the control group and the LacZ group. A mild intima injury was obtained in the Adanti-ERK2 group. The ratio of intima/（ intima ＋ media） was 7.6%, 81.4%, 85.9% and 15.9% in isograft, con- trol, LaeZ and Adanti-ERK2 groups, respectively. The α-aetin staining-positive calls, which indicated VSMCs, were counted per vision-field as O, 71.3 ±9.2, 76.4 ± 11.3 and 34. 8 ±5.3, respectively. The platelet derived growth faetor-BB （ PDGF-BB ） positive cells were counted as 0. 9 ± 0. 5, 28.4± 3.4, 29. 1 ± 3.2 and 8. 6 ±1.7, respectively. The angiogenesis was detected as none, abundant, abundant and few, and COX-2 positive cells were counted as 0, 36. 3 ± 8.3, 40. 9 ± 9. 2 and 10. 4 ± 3.9, respectively （P 〈 0.05 between Adanti-ERK2 group and other groups）. Conclusion Intimal proliferation, luminal narrow, VSMCs recruitment and differentiation induced by PDGF-BB in intima and the following angiogene- sis are the important pathophysiological process of TA. Adanti-
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2011年第4期514-516,共3页
Chinese Journal of Experimental Surgery
基金
基金项目：国家自然科学基金资助项目（30300324）
武汉市科技攻关计划资助项目（201060948360-03）
