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目的:探讨基因重组转化生长因子α-绿脓杆菌外毒素融合蛋白(TGF_α-PE40;TP40)对动脉球囊损伤后内膜增生的抑制作用。方法:40只雄性兔随机分为TP4015μg、30μg、60μg、正常动脉及生理盐水对照组(n=8),均高脂饲养。在兔右颈总动脉行球囊内膜剥脱术后24h,治疗组于动脉损伤段局部给予TP40 15μg、30μg及60μg治疗;对照组给予生理盐水。正常动脉组局部给予TP40 60μg。于治疗后第2周取实验动脉段行光镜、电镜观察及计算机图像分析。结果:光镜观察见对照组动脉内膜不规则增厚,新生内膜可见大量平滑肌细胞(SMC),管腔狭窄;TP40治疗组动脉内膜增生被明显抑制,管腔无狭窄;TP40对正常动脉影响不大;电镜观察见TP40 60μg治疗组的动脉中膜有较多变性、坏死的SMC;计算机图像分析显示动脉损伤后第2周TP40治疗组内膜截面积及内膜与中膜截面积的比值显著小于生理盐水对照组(P<0.01)。结论:TP40对动脉球囊损伤后的内膜增生具有抑制作用。
Objective: To investigate the inhibitory effect of transforming growth factor-alpha-Pseudomonas exotoxin fusion protein (TGF-α-PE40; TP40) on intimal hyperplasia after arterial balloon injury. Methods: Forty male rabbits were randomly divided into TP4015μg, 30μg, 60μg, normal artery and saline control group (n = 8). In the rabbit right common carotid artery balloon endarterectomy 24 h, the treatment group in the arterial injury segment TP40 15μg, 30μg and 60μg treatment; control group given saline. The normal arterial group was given TP40 60 μg. At the second week after treatment, the experimental arterial segments were examined by light microscopy, electron microscopy and computer image analysis. Results: In the control group, there was an irregular thickening of the intima of the arteries. A large number of smooth muscle cells (SMCs) were found in the neointima, and stenosis of the lumen was observed. Intimal hyperplasia of the TP40 group was significantly inhibited without stenosis of the arteries. Arterial microscopy showed TP40 60μg treatment group had more denatured and necrotic SMC; computer image analysis showed that the second week after arterial injury TP40 treatment group intimal cross-sectional area and intimal and medial cross-sectional area Was significantly lower than that of saline control group (P <0.01). Conclusion: TP40 has an inhibitory effect on intimal hyperplasia after arterial balloon injury.