贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响  

Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys

作　　者：杨平 崔立[1] 俞诚 温智越 YANG Ping;CUI Li;YU Cheng;WEN Zhiyue(Shanghai Jiao Tong University School Of Agriculture And Biology,Shanghai 201209,China;PharmaLegacy Laboratories(Shanghai)Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]上海交通大学农业与生物学院,上海201209 [2]澎立生物医药技术(上海)股份有限公司,上海201203

出　　处：《实验动物与比较医学》2023年第1期21-29,共9页Laboratory Animal and Comparative Medicine

基　　金：上海市科委科技计划项目-实验动物专项“基于肠类器官3D培养和高内涵成像的药物毒性和安全性评价模型研究”(21140901400)。

摘　　要：目的通过观察贝伐珠单抗注射液对食蟹猴背部皮肤伤口愈合速度及损伤皮肤组织中CD34表达的影响,验证贝伐珠单抗注射液对食蟹猴伤口愈合的延迟作用,为临床肿瘤手术患者使用贝伐珠单抗治疗时提供剂量和频次的用药参考。方法6只雄性食蟹猴采用背部全层皮肤切除术建立伤口愈合评估模型,随机选取3只食蟹猴作为生理盐水组,其余3只食蟹猴为贝伐珠单抗组。贝伐珠单抗组食蟹猴在手术后第0、4、8、11天静脉注射30 mg/kg贝伐珠单抗注射液,生理盐水组静脉注射等量生理盐水;术后进行血常规检测,并观察各组食蟹猴的伤口愈合情况,Image J软件分析伤口愈合率,用评分法对伤口状态的严重程度进行评价。4周后对6只食蟹猴伤口愈合皮肤取材,通过免疫组织化学法检查皮肤组织中CD34的表达水平。结果成功构建食蟹猴伤口愈合评估模型。术后第3天的食蟹猴血液中白细胞、中性粒细胞数量明显升高(P<0.05),第7天后白细胞数量逐渐恢复正常,而红细胞、血红蛋白、红细胞压积没有明显变化,提示动物营养状态良好。与生理盐水组相比,贝伐珠单抗组的伤口愈合率在术后7 d、28 d明显降低(P<0.01,P<0.001),愈合皮肤组织中CD34表达水平明显降低(P<0.01)。结论贝伐珠单抗注射给药可能通过抑制食蟹猴伤口新生皮肤组织中的微血管生成,延缓伤口愈合。临床中患者手术后使用贝伐珠单抗注射液时应该权衡利弊,科学合理地选择干预时间点、剂量、频次。Objective By observing the impact of Bevacizumab injection on the speed of wound healing and the expression of CD34 in cynomolgus monkeys,to verify its delayed wound healing mechanism,and to provide clinical reference for the dosage and frequency of Bevacizumab treatment for oncology surgery patients.Methods Six male cynomolgus monkeys underwent full-thickness skin resection on the back to establish a wound healing evaluation model.Three cynomolgus monkeys were randomly selected as the saline group,and the other three cynomolgus monkeys were allocated to the Bevacizumab treatment group.The monkeys of Bevacizumab group were administrated with Bevacizumab injection(30 mg/kg,i.v.)on day 0,day 4,day 8,and day 11,respectively.The monkeys of saline group were injected with the same volume of saline as the group receiving Bevacizumab.The blood routine test was conducted,and the wound healing of each group of cynomolgus monkeys was observed 28 days after operation.The wound healing rate was analyzed by software Image J,and the severity of the wound was assessed by scoring method.Wound healing skin samples of 6 cynomolgus monkeys were obtained after 4 weeks,and the expression level of CD34 in the wound skin tissues was detected using immunohistochemistry.Results A skin excision wound model has already been established in cynomolgus monkeys.The number of white blood cells and neutrophils in the blood of cynomolgus monkeys increased significantly on the 3rd day after operation(P<0.05),and the number of white blood cells gradually returned to normal on the 7th day,while the number of red blood cells,hemoglobin and hematocrit did not change significantly,suggesting that the animals were in good nutritional status.The Bevacizumab injection group wound healing rate was significantly slower than that of the saline group on day 7,and day 28(P<0.01,P<0.001).Microvessel density in the wound skin of Bevacizumab group appeared to be significantly lower than that of the saline group(P<0.01).Conclusion The injection of Bevacizumab may

关 键 词：贝伐珠单抗注射液 伤口愈合 伤口评分 CD34 食蟹猴 

分 类 号：Q95-33[生物学—动物学] R-332[医药卫生]