纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究

戴小宇; 朱海; 张晓冬; 张晓芳; 宗英; 戴益民; 张淑英; 袁伯俊; 陆国才

doi:10.3969/j.issn.1006-0111.2015.03.010

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

《药学实践与服务》杂志目前不收取审稿费、版面费、加急费等费用，如收到邮件声称是编辑部X编辑，要求加作者微信的，请谨防财产损失！编辑部用于作者校对时绑定微信的邮件通过yxsjzzs@163.com发送，标题是《药学实践与服务》XML数字出版服务微信绑定，请区分开。

纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究

戴小宇, 朱海, 张晓冬, 张晓芳, 宗英, 戴益民, 张淑英, 袁伯俊, 陆国才

文章导航 > 药学实践与服务 > 2015 > 33(3): 231-234

戴小宇, 朱海, 张晓冬, 张晓芳, 宗英, 戴益民, 张淑英, 袁伯俊, 陆国才. 纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究[J]. 药学实践与服务, 2015, 33(3): 231-234. doi: 10.3969/j.issn.1006-0111.2015.03.010

引用本文:

DAI Xiaoyu, ZHU Hai, ZHANG Xiaodong, ZHANG Xiaofang, ZONG Ying, DAI Yimin, ZHANG Shuying, YUAN Bojun, LU Guocai. Repeat-dose toxicity study of fibrin sealant in SD rats[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(3): 231-234. doi: 10.3969/j.issn.1006-0111.2015.03.010

Citation:

DAI Xiaoyu, ZHU Hai, ZHANG Xiaodong, ZHANG Xiaofang, ZONG Ying, DAI Yimin, ZHANG Shuying, YUAN Bojun, LU Guocai. Repeat-dose toxicity study of fibrin sealant in SD rats[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(3): 231-234. doi: 10.3969/j.issn.1006-0111.2015.03.010

纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究

doi: 10.3969/j.issn.1006-0111.2015.03.010

第二军医大学药物安全性评价中心, 上海 200433

基金项目: "重大新药创制"科技重大专项(2014ZX09J14106);上海市公共卫生重点实验室建设计划(12GWZX0501);上海市自然科学基金(13ZR1449400)

Repeat-dose toxicity study of fibrin sealant in SD rats

Center for New Drug Evaluation, Second Military Medical University, Shanghai 200433, China

摘要: 目的评价SD大鼠连续腹腔注射纤维蛋白封闭剂的安全性。方法 SD大鼠雌雄分别按体质量随机分4组, 即空白对照组、纤维蛋白封闭剂低剂量组、中剂量组和高剂量组, 每组20只, 雌雄各半。3个给药组的给药剂量分别为85.5、171.0和342.0 mg/kg, 每天腹腔注射给药, 连续14 d, 恢复期28 d, 进行一般症状、血液学、血液生化和病理组织学等指标检测。结果与空白对照组相比, 纤维蛋白封闭剂中、高剂量组大鼠第14天的白细胞计数显著升高, 纤维蛋白原显著降低, 中、高剂量组大鼠脾脏的脏器重量有增加趋势。组织病理学检查发现部分高剂量动物腹腔出现残留药物引起的纤维肉芽组织包裹。上述变化指标在恢复期结束时基本可恢复。结论大鼠腹腔注射纤维蛋白封闭剂85.5~342.0 mg/kg, 安全剂量为85.5 mg/kg, 毒性剂量为171.0 mg/kg。毒性靶系统或靶部位为血液系统、免疫系统和给药局部, 毒性作用可逆。
- 纤维蛋白封闭剂 /
- SD大鼠 /
- 重复给药毒性 /
- 临床前安全性
Abstract: Objective To evaluate the safety of fibrin sealant (FS) intraperitoneal injection in SD rats. Methods 80 male and female SD rats were randomly divided into four groups (0, 85.5, 171.0, 342.0 mg/kg) by body weight. All rats were intraperitoneally injected with vehicle or FS daily for 14 days followed by a 28-day recovery period. The clinical signs, hematological and biochemical indices were measured. The pathology were observed. Results Increase of white blood cell count (WBC) and decrease of fibrinogen (FIB) in d 14 were found in 171.0 mg/kg and 342.0 mg/kg dosage groups. Furthermore, the tendency of weight increase of spleen were found in 171.0 mg/kg and 342.0 mg/kg dosage groups. Pathological exams of peritoneal cavity found that there were granulation tissues containing FS in some of the rats in 342.0 mg/kg group. All of these changes got reversed after the recovery period. Conclusion The safety dose in this study is considered to be 85.5 mg/kg, and the toxicity dose is 171.0 mg/kg. The target toxicity systems or site of FS in SD rats are hematological system, immune system and injection site. The toxic effects of FS are reversible.
- fibrin sealant /
- SD rats /
- repeat-dose toxicity /
- preclinical safety

[1]	Spotnitz WD.Hemostats,sealants,and adhesives:a practical guide for the surgeon[J].Am Surg,2012,78(12):1305-1321.
[2]	王平瑜,白雪峰,王保卫,等.人纤维蛋白胶对人肝损伤的止血护创作用[J].中国医学创新,2011,8(6):9-11.
[3]	谢钧韬,叶建宇,尹耀新,等.纤维蛋白封闭剂在腹腔镜胆囊切除术右副肝管处理中的应用[J].中华腔镜外科杂志(电子版),2010,3(2):205-207.
[4]	Mao Y, Xia ZN, Zhang XF,et al.Evaluation of subchronic toxicity of SIM010603,a potent inhibitor of receptor tyrosine kinase,after 28-day repeated oral administration in SD rats and beagle dogs[J].Food Chem Toxicol,2012,50(5):1256-1270.
[5]	Gong XL, Gao TT, Zhao LJ,et al.Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri)in Sprague-Dawley rats and beagle dogs[J].Regul Toxicol Pharmacol,2014,69(3):558-571.
[6]	王春仁,王召旭,宋谊萍,等.医用纤维蛋白胶亚急性毒性实验研究[J].中国药事杂志,2007,21(7):472-477.
[7]	Bjorenson JE,Grove HF,List MG Sr,et al.Effects of hemostatic agents on the pH of body fluids[J].J Endod,1986,12:289.
[8]	Ibrahim MF,Aps C,Young CP.A foreign body reaction to Surgicel mimicking an abscess following cardiac surgery[J].Eur J Cardiothorac Surg,2002,22(3):489-490.
[9]	Chapman WC,Wren SM,Lebovic GS,et al.Effective management of bleeding tumor resection with a collagen-based hemostatic agent[J].Am Surg,2002,68(9):802-807.
[10]	Tomizawa Y.Clinical benefits and risk analysis of topical hemostats: a review [J].J Artif Organs,2005,8(3):137-142.

[1]	魏莱, 董国强, 盛春泉. 靶向SARS-CoV-2主蛋白酶的PROTAC设计、合成与蛋白降解活性研究 . 药学实践与服务, 2025, 43(5): 235-241, 258. doi: 10.12206/j.issn.2097-2024.202503063
[2]	冯婷婷, 张景翔, 王彦, 许维恒, 张俊平. ANXA3基因及蛋白的研究进展 . 药学实践与服务, 2025, 43(2): 47-50, 74. doi: 10.12206/j.issn.2097-2024.202309023
[3]	肖农, 陆诗依, 唐文雅, 居敏俐, 徐刚锋, 杨明华. 中成药微生物计数法前处理的影响因素和优化方法 . 药学实践与服务, 2025, 43(): 1-5. doi: 10.12206/j.issn.2097-2024.202403014
[4]	刘桂株, 李行, 王楠, 王芳, 胡旭, 汤佳洁. 信息技术在我国用药安全领域应用的计量分析 . 药学实践与服务, 2025, 43(): 1-7. doi: 10.12206/j.issn.2097-2024.202303027
[5]	姜建芳, 王思平, 何新军. 硝苯地平在高血压孕妇中的药物毒性：基于FARES数据库的真实世界研究 . 药学实践与服务, 2025, 43(6): 307-312. doi: 10.12206/j.issn.2097-2024.202501001
[6]	张俊丽, 李媛媛, 尹静, 杨鸿源, 白耀武. 咪达唑仑调节PINK1/PARKIN信号通路对缺血性脑卒中大鼠神经元损伤的影响 . 药学实践与服务, 2025, 43(6): 288-292, 312. doi: 10.12206/j.issn.2097-2024.202405024
[7]	竺东杰, 贺新征, 邹杰, 余史丹, 李红霞. 雷公藤甲素对大鼠脑缺血再灌注损伤的影响及机制研究 . 药学实践与服务, 2025, 43(): 1-6. doi: 10.12206/j.issn.2097-2024.202311021
[8]	于翔, 贾培培, 李欣颖, 杨君君, 郭高峰, 陆连芳. M2型巨噬细胞外泌体喷剂对压力性损伤的疗效及作用机制 . 药学实践与服务, 2025, 43(): 1-7. doi: 10.12206/j.issn.2097-2024.202503066
[9]	底雪梅, 帅文, 张其锵, 余梅香, 张海, 聂永红. 暖宫外敷方预防宫腔再粘连临床疗效回顾性分析 . 药学实践与服务, 2025, 43(): 1-4. doi: 10.12206/j.issn.2097-2024.202411013
[10]	魏莱, 董国强. SARS-CoV-2主蛋白酶抑制剂和降解剂研究进展 . 药学实践与服务, 2025, 43(6): 259-269, 297. doi: 10.12206/j.issn.2097-2024.202503064
[11]	郭静, 康金龙, 李强, 赵琳, 刘骥, 徐学武. 利多卡因不同给药途径对麻醉诱导气管插管心血管应激反应的抑制作用 . 药学实践与服务, 2025, 43(6): 303-306. doi: 10.12206/j.issn.2097-2024.202502009
[12]	徐尧, 马春辉, 李志勇. 高血压对大鼠心血管纤维化及sFRP2表达的影响 . 药学实践与服务, 2025, 43(4): 180-184. doi: 10.12206/j.issn.2097-2024.202409055
[13]	冯一帆, 严啸东, 张文彬, 李炳锋, 郭美丽. 菸花苷长期给药对脑缺血再灌注损伤大鼠神经功能的影响 . 药学实践与服务, 2025, 43(5): 228-234. doi: 10.12206/j.issn.2097-2024.202407038
[14]	魏雨辰, 田家盛, 王道鑫, 凌期盛, 王治, 缪朝玉. 烟酰胺单核苷酸口服给药对高血压大鼠的影响 . 药学实践与服务, 2025, 43(5): 213-221. doi: 10.12206/j.issn.2097-2024.202412006
[15]	刘依秦, 王超群, 邱娇娜. 胆宁片预处理在糖尿病患者结肠镜检查前的应用效果分析 . 药学实践与服务, 2024, 42(9): 407-410. doi: 10.12206/j.issn.2097-2024.202407037
[16]	张晶晶, 索丽娜, 郑兆红. 89例细菌性肝脓肿的临床特征及抗感染治疗分析 . 药学实践与服务, 2024, 42(6): 267-272. doi: 10.12206/j.issn.2097-2024.202302039
[17]	张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英. 二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
[18]	王耀振, 徐灿, 吕顺莉, 田泾, 张东炜. 钾离子竞争性酸阻滞剂的药学特征研究进展 . 药学实践与服务, 2024, 42(7): 278-284. doi: 10.12206/j.issn.2097-2024.202306040
[19]	陈炳辰, 佟达丰, 万苗, 闫飞虎, 姚建忠. UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究 . 药学实践与服务, 2024, 42(8): 341-345. doi: 10.12206/j.issn.2097-2024.202404082
[20]	刘丽艳, 余小翠, 孙传铎. 纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044

点击查看大图

计量

文章访问数: 4420
HTML全文浏览量: 368
PDF下载量: 1027
被引次数: 0

纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究

doi: 10.3969/j.issn.1006-0111.2015.03.010

第二军医大学药物安全性评价中心, 上海 200433

基金项目: "重大新药创制"科技重大专项(2014ZX09J14106);上海市公共卫生重点实验室建设计划(12GWZX0501);上海市自然科学基金(13ZR1449400)

收稿日期: 2014-08-27
修回日期: 2014-12-30

关键词:

纤维蛋白封闭剂 /

SD大鼠 /

重复给药毒性 /

临床前安全性

摘要: 目的评价SD大鼠连续腹腔注射纤维蛋白封闭剂的安全性。方法 SD大鼠雌雄分别按体质量随机分4组, 即空白对照组、纤维蛋白封闭剂低剂量组、中剂量组和高剂量组, 每组20只, 雌雄各半。3个给药组的给药剂量分别为85.5、171.0和342.0 mg/kg, 每天腹腔注射给药, 连续14 d, 恢复期28 d, 进行一般症状、血液学、血液生化和病理组织学等指标检测。结果与空白对照组相比, 纤维蛋白封闭剂中、高剂量组大鼠第14天的白细胞计数显著升高, 纤维蛋白原显著降低, 中、高剂量组大鼠脾脏的脏器重量有增加趋势。组织病理学检查发现部分高剂量动物腹腔出现残留药物引起的纤维肉芽组织包裹。上述变化指标在恢复期结束时基本可恢复。结论大鼠腹腔注射纤维蛋白封闭剂85.5~342.0 mg/kg, 安全剂量为85.5 mg/kg, 毒性剂量为171.0 mg/kg。毒性靶系统或靶部位为血液系统、免疫系统和给药局部, 毒性作用可逆。

English Abstract

Repeat-dose toxicity study of fibrin sealant in SD rats

Center for New Drug Evaluation, Second Military Medical University, Shanghai 200433, China

Received Date: 2014-08-27
Rev Recd Date: 2014-12-30

Keywords:

Abstract: Objective To evaluate the safety of fibrin sealant (FS) intraperitoneal injection in SD rats. Methods 80 male and female SD rats were randomly divided into four groups (0, 85.5, 171.0, 342.0 mg/kg) by body weight. All rats were intraperitoneally injected with vehicle or FS daily for 14 days followed by a 28-day recovery period. The clinical signs, hematological and biochemical indices were measured. The pathology were observed. Results Increase of white blood cell count (WBC) and decrease of fibrinogen (FIB) in d 14 were found in 171.0 mg/kg and 342.0 mg/kg dosage groups. Furthermore, the tendency of weight increase of spleen were found in 171.0 mg/kg and 342.0 mg/kg dosage groups. Pathological exams of peritoneal cavity found that there were granulation tissues containing FS in some of the rats in 342.0 mg/kg group. All of these changes got reversed after the recovery period. Conclusion The safety dose in this study is considered to be 85.5 mg/kg, and the toxicity dose is 171.0 mg/kg. The target toxicity systems or site of FS in SD rats are hematological system, immune system and injection site. The toxic effects of FS are reversible.

引用本文: