PLGA/PEG可吸收电纺聚合膜对大鼠腹腔术后粘连的预防作用研究

Study on the prevention of postoperative intraperitoneal adhesion of rat with PLGA/PEG electrospun polymer membrane

目的采用聚乳酸/乙醇酸共聚物(poly-L-lactic/glycolic acid,PLGA)、聚乙二醇(polyethylene glycol,PEG)以静电纺丝技术制备PLGA/PEG可吸收电纺聚合膜,探讨其对大鼠腹腔术后粘连的预防作用。方法将PLGA和PEG按照19∶1(M/M)混合后溶解于有机溶剂中,采用静电纺丝技术制备PLGA/PEG可吸收电纺聚合膜,并行大体及扫描电镜观察。取SD大鼠54只,体质量180~200 g,随机分为3组,其中正常对照组6只,不进行任何处理;模型组及PLGA/PEG组各24只,采用盲肠浆膜机械损伤方法制备腹腔粘连模型,术中PLGA/PEG组盲肠创面局部覆盖PLGA/PEG可吸收电纺聚合膜,模型组不进行任何处理。术后3 d及1、2、8周,大体观察腹腔粘连情况并参照自定标准对腹腔粘连程度进行评级,PLGA/PEG组观察PLGA/PEG可吸收电纺聚合膜降解情况;各时间点取标本进行组织学观察;以上指标均与正常对照组进行比较。结果采用静电纺丝技术成功制备PLGA/PEG可吸收电纺聚合膜,呈白色、不透明状,质地柔软;扫描电镜观察示,PLGA/PEG可吸收电纺聚合膜主要由纤维无序交错堆积而成,具备微孔结构。术后大鼠均存活至实验完成。大体观察示,PLGA/PEG可吸收电纺聚合膜植入大鼠体内后,随时间延长逐渐降解;PLGA/PEG组腹腔粘连程度较模型组显著降低,各时间点粘连分级比较差异均有统计学意义(P<0.05),但尚未达正常对照组水平(P<0.05)。组织学观察示,各时间点与模型组相比,PLGA/PEG组盲肠纤维结缔组织增生明显减缓,粘连程度明显降低,仅见少量炎性细胞浸润;但尚未达正常对照组水平。结论 PLGA/PEG可吸收电纺聚合膜能有效预防大鼠术后腹腔粘连,并具有良好生物降解性。

Objective Adopting poly-L-lactic/glycolic acid （PLGA） and polyethylene glycol （PEG） as the material to fabricate PLGA/PEG electrospun polymer membrane by electrospinning technology. And to study its preventive effect on postoperative intraperitoneal adhesion of rat. Methods PLGA and PEG were mixed at the ratio of 19 ; 1（M/M）, then dissolved in organic solvent. The PLGA/PEG electrospun polymer membrane was prepared by electrospinning technology, and then the gross observation and scanning electron microscope observation were taken. Fifty-four Sprague Dawley rats （weighing, 180-200 g）, were randomly divided into 3 groups. The rats in control group （n=6） were left intact. The rats in model group （n=24） and PLGA/PEG group （n=24） were treated with the method of mechanical injury of the cecal serosa in order to establish the intraperitoneal adhesion models; then the PLGA/PEG electrospun polymer membrane was used to cover the wound in PLGA/PEG group, but was not in the model group. The intraperitoneal adhesion in PLGA/PEG group and model group were observed at 3 days, 1 week, 2 weeks, and 8 weeks after operation, and the adhesion degree was assessed according to the self-generated standard. The degradation of PLGA/PEG electrospun polymer membrane was also observed in PLGA/PEG group. At each time point, the rats were harvested for histological observation. All the above indexes were compared with the control group. Results Using the electrospinning technology, PLGA/PEG electrospun polymer membrane was prepared successfully. PLGA/PEG electrospun polymer membrane was white and opaque, with soft texture. Scanning electron microscopy observation showed that PLGA/PEG electrospun polymer membrane was mainly composed of disorderly staggered fibers, with microporous structure. All rats survived to the end of the experiment. Gross observation showed that PLGA/PEG electrospun polymer membrane gradually degraded after implantation in vivo, and the adhesion degree in PLGA/PEG group was significantly lower than that in model group （P〈0.05）, but it had not yet reached to the level of the control group （P〈0.05）. Histological observation showed that the proliferation of cecal fibrous connective tissue was slower in PLGA/PEG group than in model group, and adhesion severity significantly decreased, only with a small amount of inflammatory cell infiltration. Nevertheless, it was not up to the level of the control group. Conclusion PLGA/PEG electrospun polymer membrane can effectively prevent postoperative intraperitoneal adhesion of rat, and has good biodegradability.