PGLA降解产物对机体主要生理功能的影响

降解产物的生物安全性是生物降解类材料生物学评价的重要内容。本文采用自体对照的方法,通过测定聚乙交酯丙交酯(PGLA)材料植入前后动物体内某些生化指标的变化,研究降解产物对机体主要脏器——肝肾功能的影响,探讨降解产物的在体生物可接受性。实验分别将不同大小的PGLA材料植入Wistar大白鼠和新西兰兔的背部皮下组织内,在动物的相同部位进行同样的手术切口和缝合作为对照,植入前和植入后2~10周的各不同时段,分别采集兔血和大鼠的尿液,测定尿素氮和尿肌酐、血清谷丙转氨酶、尿素和肌酐等生化指标。结果显示:植入后2~3周实验组尿样中的尿素氮和尿肌酐浓度出现明显的增高,与植入前比较,统计学上具有显著性差异(P<0.01);植入后第2周血清谷丙转氨酶略有所下降(P<0.05),而血尿素和血肌酐有较明显的增高(P<0.01),但自第4周起所有变化均恢复到了植入前的水平,且基本维持在一个相对恒定的范围。对照组手术前后的所有指标均未见明显的变化(P>0.05)。由此提示:(1)PGLA降解产物对肾脏和肝脏组织无永久性的损伤;(2)选用自体对照法,通过检测动物血液和尿液中主要生化指标的变化来评价PGLA降解产物对生物体全身生物学的影响作用被初步证明是一种有效而可行的研究方法;(3)在活体上评价降解产物的生物可接受性具有客观、灵敏、减少动物使用数量、可直接观察体内动态变化、能评估产物对生理功能影响等优点,为生物可降解材料的生物学评价提供新的检测途径。

Influence of PGLA Degradable Products on Main Physiologic Function

The biological safety of degradable products is a key point in biological evaluation of biodegradable materials.This paper deals with an investigation of the influence of PGLA degradable products on physiologic function of liver and kidney by detecting the "before-after change"of some biochemical indexes with the use of self-control method.PGLA materials of different sizes were implanted into the subcutaneous tissue of Wistar rats and New Zealand rabbits respectively.Also for the purpose of group comparison,only surgical operation was performed on other animal at the same site(control group).The concentrations of urea nitrogen,uric creatinine,blood urea nitrogen(BUN),carbamide(Cr) and serum glutamio pyruvic transaminase(GPT) were measured before and after implantation(from 2 w to 10 w).The results showed the values of urea nitrogen and uric creatinine were significantly increased at 2-3 weeks after implantation(P<0.01).After 2 weeks of implantation,the concentration of GPT was slightly decreased(P<0.05).The BUN and Cr were remarkably increased(P<0.01).But at the 4th week,all the values returned to normal and kept stable thenceforth.All the biochemical indexes in the control animal exhibited no abnormal change after operation.These results indicated:(1)There are no permanent harmful effects of PGLA degradable products on the function of liver and kidney;(2) By means of self-control and measurements of some biochemical indexes in the blood or urea,the method is suitable for evaluating the biological safety of degradable products;(3) The method has the advantages for evaluating the bioaccept ability of degradable products during the life period,it is objective and sensitive,the number of animal can be decreased,the process of dynamic change in vivo can be observed directly,and the effect of degradable products on physical function can be evaluated.Therefore,the method can provide a new approach for biological evaluation of biodegradable materials.