草酸铂腹腔化疗腹膜急慢性反应的动物研究

Acute and Chronic Peritoneal Toxicity Observation in the Rats Undertaking Peritoneal Chemotherapy With Oxaliplatin

目的:探讨草酸铂腹腔化疗所致腹膜炎样症状的原因。方法:本实验以小鼠草酸铂腹腔灌注模型作为研究对象,随机分成6组,每组16只,分别接受:A组(对照组):每只小鼠腹腔内注射5%葡萄糖注射液1 mL。B组(低浓度组):每只小鼠腹腔内注射浓度为250μg/mL的奥沙力铂葡萄糖溶液1 mL。C组(高浓度组):每只小鼠腹腔内注射浓度为500μg/mL的奥沙力铂葡萄糖溶液1 mL。处理后24小时用颈椎脱臼法处死三组各8只小鼠,解剖并观察腹膜急性炎症反应:一、腹水:按量及外观分别记为1(无)、2(中等量或外观混浊)、3(大量或外观血性);二、腹膜充血和渗出:观察脏层及壁层腹膜充血和渗出记为1(无明显充血和渗出)、2(明显充血但无渗出)、3(明显充血伴非血性渗出)、4(局部出血)。三、组织病理学指标:取局部充血较明显的脏层或壁层腹膜标本,经10%甲醛溶液浸泡固定,HE染色后显微镜下观察炎症反应程度并记为1(每高倍镜视野内少于10个炎细胞侵润)、2(每高倍镜视野内多于10个炎细胞侵润或伴纤维素渗出)、3(炎症伴出血)。三组剩余的小鼠于处理后一月用颈椎脱臼法处死,解剖并观察腹膜慢性炎症反应:一、大体观:按腹膜有无增厚、肠系膜有无粘连记为1(无)、2(轻度)、3(重度);二:镜下观:取局部充血较明显的脏层或壁层腹膜标本,经10%甲醛溶液浸泡固定,HE染色后显微镜下观察炎症反应程度并记为1(腹膜基本正常,无明显慢性炎症反应)、2(视野内可见淋巴细胞浸润,无明显纤维母细胞及胶原纤维分布)、3(大量淋巴细胞浸润,并有明显的纤维母细胞及胶原纤维分布)。结果:三组小鼠均无明显腹膜急慢性炎症反应表现。结论:草酸铂腹腔化疗并不会直接导致腹膜的急慢性炎症。临床使用草酸铂腹腔化疗所观察到的急性腹部症状不能以化学性腹膜炎来解释。

Objective: To probe the cause of the acute abdominal symptoms of the patients undertaking peritoneal chemotherapy with oxaliplatin.Methods: 48 white rats were randomized into 3 groups: Group A,B and C.Group A received peritoneal injection with 1ml 5% glucose solution for injection as controls.Group B(low concentration group) were peritoneally administered with 1ml low concentration oxaliplatin solution(250 μg oxaliplatin in 1ml 5% glucose solution for injection).Group C(high concentration group) were peritoneally injected with 1ml high concentration oxaliplatin solution(500 μg oxaliplatin in 1ml 5% glucose solution for injection).24 hours later half of the rats were sacrificed and undertaken abdominal dissection to be evaluated the acute peritonitis using the following parameters:1.ascites: scored according the quality and quantity as 1(no ascites),2(moderate amount and/or turbid appearance) and 3(large amount and/or bloody appearance);2.peritoneal congestion and exudation: scored as 1(non congestion and exudates),2(apparent congestion without exudate),3(apparent congestion with non-bloody exudates),4(bloody exudates);3.histopathological index: parietal and visceral peritoneal tissues with grossly congested features were sampled and fixed by 10% formalin and followed by hematoxylin and eosin stain.Then the acute inflammatory severity was scaled through microscopic examination as following: 1(none or less than 10 inflammatory cells per HP),2(more than 10 inflammatory cells per HP and/or with fibrous exudates);3(hemorrhagic inflammation).The rest of the rats were killed 1 month later.The chronic inflammation of peritoneal tissues were evaluated grossly at first,according the extent and severity of peritoneal thickness and adhension,as 1(non),2(moderate),3(severe).Then tissues were dissected and prepared in the same way.Microscopic evaluation were done and scored as: 1(basically normal apperance),2(infiltration of lymph cells without fibroblasts and collagens),3((infiltration of lymph cells with fibroblasts and collagens).Results: no apparent acute and chronic peritoneal inflammations were observed in all three groups.The score of the high concentration group was slightly higher than the rest groups without statistics significance.Conclusions:peritoneal chemotherapy with oxaliplatin will not cause acute peritonitis and the acute abdominal symptoms of the patients undertaking peritoneal chemotherapy with oxaliplatin can not be due to the drug-induced chemical peritonitis.