摘要
目的:探讨不同浓度平阳霉素对兔正常唇组织的影响。方法:31只家兔随机分为3组:8 mg/5 ml剂量组(15只家兔)、8 mg/3 ml剂量组(15只家兔)和对照组(1只家兔)。2剂量组家兔再分别分为5个亚组(每亚组3只家兔),各亚组家兔右侧上唇分别注射8 mg/5 ml和8 mg/3 ml平阳霉素各0.5 ml,对照组家兔右侧上唇注射同体积生理盐水。每天观察兔唇部改变。第1次注射后第2周重复注射1次。2个剂量组于第1次注射后第21,28,35,60,90天分别处死各亚组3只家兔,空白组家兔于注射后第90天处死。观察注射部位不良反应,测量注射后不同时间点唇部的厚度。用光镜和透射电镜观察兔唇部组织的病理改变。结果:8 mg/5 ml剂量组在第1次注射后第21,28,35,60及90天未见兔双侧上唇不对称性改变,兔唇注射处厚度分别为(4.18±0.04)mm、(4.16±0.06)mm、(4.16±0.03)mm、(4.14±0.05)mm和(4.12±0.02)mm。8 mg/3 ml剂量组在第1次注射后的各时间点,兔上唇注射部位肿胀,上唇略有萎缩及局部黏膜硬化,兔唇注射处厚度分别为(3.48±0.01)mm、(3.36±0.02)mm、(2.64±0.11)mm、(1.56±0.14)mm和(1.38±0.18)mm。2组比较不同时间点兔唇注射处厚度差异有统计学意义(均P<0.01)。注射后第28天,光镜检查8 mg/3 ml剂量组兔唇注射部位组织示:血管内皮细胞空泡样变性,血管腔内血栓形成,管腔阻塞,胶原纤维增生变性,部分肌纤维被胶原纤维取代。注射后第90天,电镜观察示:8 mg/5 ml剂量组兔线粒体正常,嵴清晰,肌纤维排列整齐,与空白对照组相似;8 mg/3 ml剂量组兔部分肌纤维溶解、肌丝肿胀、线粒体外膜破裂,嵴溶解,一些线粒体空泡样变性。结论:兔唇正常组织局部注射8 mg/5 ml平阳霉素比8 mg/3 ml平阳霉素安全。
Objective： To investigate the effect of different pingyangmycin concentrations on normal rabbit lip tissue. Methods： Thirty-one rabbits were randomly divided into three group： the 8 mg/5 ml dose group （ 15 rabbits）, the 8 mg/3 ml dose group （ 15 rabbits）, and the control group （one rabbit）. The rabbits in both dose groups were redivided into 5 subgroups （3 rabbits in each subgroup） , respectively. The rabbit right upper lip in the each subgroup was injected with 0.5 ml of pingyangmycin 8 mg/5 ml and pingyangmycin 8 mg/3 ml, respectively. The rabbit right upper lip in the control group was injected with same volume of normal saline. The changes in the rabbit lip were observed every day. The repeated injection was performed on week 2 ＇after the first injection. Three rabbits in each subgroup of both dose groups were sacrificed on days 21,28,35,60, and 90 after the first injection and the rabbit in the control group was sacrificed on day 90 after the first injection. Adverse reactions at the local injection site were observed, and the lip thickness was measured at the different time points after injection. The pathological changes in the rabbit lip tissue were observed under light microscope and transmission electron microscope. Results： In the 8 mg/5 ml dose group, asymmetric changes in the rabbit bilateral upper lip were not found and the thickness of injection site of the rabbit lip was respectively （4.18 ± 0.04 ） mm, （ 4. 16 ± 0.06 ） mm, （4.16 ± 0.03 ） mm, （4.14 ± 0.05 ） mm, and （4.12 ± 0.02 ） mm on days 21, 28, 35, 60, and 90 after the first injection. In 8 mg/3 ml dose group, swelling of injection site of the rabbit upper lip, mild atrophy of upper lip, and sclerosis of local mucous membrane occurred, and the thickness of injection site of the rabbit lip was respectively （ 3.48 ± 0.01 ） mm, （ 3.36 ± 0.02 ） ram, （2.64 ± 0.11 ） mm, （ 1.56 ± 0.14） mm, and （ 1. 38 ± 0.18 ） mm at different time points after the first injection. The differences in the thickness of injection site of the rabbit lip at different time points between the 8 mg/5 ml dose group and the 8 mg/3 ml dose group were statistically significant （ all P 〈 0.01 ）. On day 28 after injection, light microscopic examination of the rabbit lip tissue from injection site in the 8 mg/3 ml dose group revealed vacuolar degeneration of vascular endotheliocyte, intravascular thrombosis and obstruction, hyperplasia and degeneration of collagenous fibers, and a replacement of a part of muscle fibers by collagenous fibers. On day 90 after injection, electron microscopic examination revealed normal mitochondria, clear mitochondrial cristae, regular arrangement of muscle fibers in the 8 mg/5 ml dose group, as with the control group; and dissolution of a part of muscle fibers, swelling of myofilaments, rupture of mitochondrial outer membrane, dissolution of mitochondrial cristae, and vacuolar degeneration of some mitochondria in the 8 mg/3 ml dose group. Conclusion： Local injection of pingyangmycin 8 mg/5 ml in the normal rabbit lip tissue is safer than that of pingyangmycin 8 mg/3 ml.
出处
《药物不良反应杂志》
2009年第3期174-178,共5页
Adverse Drug Reactions Journal
