Gao Qing-Hong, Zheng Geng-Jian, Wang Xiao-Yi, Zhou Lan, Dong Jia-Zeng, Wang Chang-Mei, Wen Yu-Ming
Department of Oral and Maxillofacial Surgery, College of West China Stomatology , Sichuan University. Chengdu 610041, China.
Shanghai Kou Qiang Yi Xue. 2005 Feb;14(1):42-7.
The aim of this study was to investigate the mechanism of Pingyangmycin-albumin microspheres (PYM-AMS) acted on the rabbit central auricular arteries.
In the study of randomized block design, 24 Japanese white rabbits were divided into 4 groups, 6 rabbits in each group. The animals were put on the operation table after being anaesthetized by intramuscular injection of Xumianxin (0.2 ml/Kg) and the interior division was blocked to stop drug liquid get into the interior ear. After being sterilized with 75% alcohol, No.1(PYM hydrochloride injection+0.9% NaCl), No.2(PYM+soybean oil), No.3(PYM-AMS+soybean oil) liquids which contained PYM 5mg/ml were injected into the central auricular arteries of the animals about 30 seconds (0.26 ml/per ear), respectively. Then these vessels were examined histologically after 2,7, 14, 21 days respectively.
After injection, in PYM+0.9% NS control group (No.1 liquid), the ears and vessels had no significant changes. In PYM+soybean oil control group (No.2 liquid), at the 2nd day, the endothelial cells were mild swollen. At the 7th day, some endothelial cells were dropped off. At the 14th day, the central auricular arteries had mild change, but the blood flow was not blocked. At the 21st day, the wall of the central auricular artery had more layers, especially on the intima, but the lumen was still obvious. A few of endothelial cells were proliferative. In PYM-AMS group(No.3 liquid), the blood was not resumed at once, and there was some oil in the vessels. At the 1st day, the injection site was mild swollen, and small thrombosis was observed in small vessels. At the 7th-14th day, the central auricular arteries were narrowed, but the blood could be observed. At the 21st day, the vessels had sclerostenosis, and the blood flow was blocked, but no scar and necrosis were observed. Under light microscopy, at the 2nd day, the endothelial cells were mild swollen and small vessels were embolized by PYM-AMS. At the 7th day, the endothelial cells were mild swollen. At the 14th day, the endothelial cells were proliferative and the wall of the central auricular artery had more layers. The lumen of the central artery changed mildly, while the surface of PYM-AMS was absorbed. At the 21st day, the wall of the central auricular artery was proliferative obviously and the artery became sclerostenosed, while cell division was observed. The PYM-AMS was obviously absorbed and some artery was sclerostenosed, while the wall of small vein was proliferative, too. The proliferative intima was proved to be muscle cells with Masson stain and van Gieson's stain. There were many smooth muscle cells, fibroblasts, myofibroblasts in the original blood vascular lumen on the 21st day under electron microscopy.
Pingyangmycin nonspecifically made the endothelia and vessels injured, and induced proliferation of endothelial cells and smooth muscle cells, and gradually the vessels became sclerostenosed. PYM-AMS had both sustained-releasing effect and embolization effect. PYM-AMS may be a better drug for treatment of large venous malformations and arteriovenous malformations.
本研究旨在探讨平阳霉素白蛋白微球(PYM-AMS)作用于兔耳中央动脉的机制。
采用随机区组设计,将24只日本大耳白兔分为4组,每组6只。动物经肌肉注射速眠新(0.2 ml/Kg)麻醉后置于手术台上,阻断内耳分支以防止药液进入内耳。用75%酒精消毒后,将含5mg/ml平阳霉素的1号液(平阳霉素盐酸盐注射液+0.9%氯化钠)、2号液(平阳霉素+大豆油)、3号液(PYM-AMS+大豆油)分别于约30秒内注入动物耳中央动脉(每耳0.26 ml)。然后分别于2、7、14、21天对这些血管进行组织学检查。
注射后,平阳霉素+0.9%生理盐水对照组(1号液),耳部及血管无明显变化。平阳霉素+大豆油对照组(2号液),第2天内皮细胞轻度肿胀;第7天,部分内皮细胞脱落;第14天,耳中央动脉有轻度改变,但血流未阻断;第21天,耳中央动脉壁层数增多,尤其是内膜,但管腔仍明显,少数内皮细胞增生。PYM-AMS组(3号液),血液未立即恢复,血管内有一些油。第1天,注射部位轻度肿胀,小血管内可见小血栓形成;第7-14天,耳中央动脉狭窄,但仍可见血流;第21天,血管发生硬化性狭窄,血流阻断,但未见瘢痕及坏死。光镜下,第2天,内皮细胞轻度肿胀,小血管被PYM-AMS栓塞;第7天,内皮细胞轻度肿胀;第14天,内皮细胞增生,耳中央动脉壁层数增多,中央动脉管腔轻度改变,同时PYM-AMS表面被吸收;第21天,耳中央动脉壁明显增生,动脉硬化性狭窄,可见细胞分裂,PYM-AMS明显被吸收,部分动脉硬化性狭窄,小静脉壁也增生。经Masson染色和Van Gieson染色证实增生的内膜为肌细胞。电镜下,第21天,原血管腔内有许多平滑肌细胞、成纤维细胞、肌成纤维细胞。
平阳霉素可非特异性损伤内皮细胞及血管,诱导内皮细胞和平滑肌细胞增生,血管逐渐硬化性狭窄。PYM-AMS具有缓释和栓塞双重作用。PYM-AMS可能是治疗大静脉畸形和动静脉畸形的较好药物。