单次鼻滴入油酸对SD大鼠的呼吸系统急性损伤作用  

Acute Respiratory Injury on Rats after A Single Intranasal Administration of Oleic Acid

作　　者：胡天羽[1] 李华[1] 马璟[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,国家上海新药安全评价研究中心,上海201203

出　　处：《中国医药工业杂志》2013年第2期166-170,共5页Chinese Journal of Pharmaceuticals

基　　金：上海市科学技术委员会专项基金(10DZ2290300)

摘　　要：将SD大鼠70只随机分为阴性对照组、博来霉素(5 mg/kg)对照组和油酸3个剂量(12、60和120 mg/kg)组,均采用单剂量鼻滴入给药。测定给药后0.5、1、2、4和8 h时动物的呼吸频率、潮气量和每分通气量。给药后d3、d7和d21分批处死动物。取左肺叶进行支气管肺泡灌洗,进行灌洗液(BALF)中炎症细胞总数和分类计数,并测定全蛋白浓度和乳酸脱氢酶(LDH)活性;另取右肺上叶测定羟脯氨酸(HYP)含量,右肺下叶用于组织病理学观察。结果表明,油酸3个剂量组在0.5 h时的呼吸频率均明显高于阴性对照组,而潮气量则明显降低。与阴性对照组相比,油酸高剂量组的BALF中炎症细胞总数、中性粒细胞、嗜酸性粒细胞明显增多,蛋白含量、LDH活性增大,肺组织病理切片可见炎性改变及泡沫细胞产生。油酸3个剂量组中HYP含量与阴性对照组均无显著差异(P>0.05)。提示高剂量油酸可致SD大鼠肺组织急性损伤并影响呼吸功能,但该效应可逆。Seventy SD rats were randomly divided into the following 5 groups： blank control, bleomycin （5 mg/kg） and oleic acid （12, 60 and 120 mg/kg） groups. All test animals were administered intranasally at a single dose. Their respiratory rate （R-R）, tidal volume （TV） and minute volume （MV） were recorded by computer at 0.5, 1, 2, 4 and 8 h after administration. The animals were sacrificed in three batches on d3, d7, d21. The respiratory toxicity effect of oleic acid was evaluated according to total and classified inflammatory cell count, protein concentration and lactate dehydrogenase （LDH） activity in the bronchoalveolar lavage fluid （BALF） of the left lobe of lung. The hydroxyproline （HYP） content in right upper lobe of lung was determined and the histopathologic changes of right lower lobe were observed. The results showed that the RR level at 0.5 h of three oleic acid groups were obviously higher than that of blank control group, while the TV level were lower. Compared with the blank control group, the total number of inflammatory cells, neutrophilic granulocyte, eosinophilic granulocytes, protein concentration and LDH activity in BALF in high dose group of oleic acid were significantly increased and lung section showed inflammatory response and numerous foam cells. There were no significant differences between three oleic acid groups and blank control group in HYP content. It indicated that high dose of oleic acid had an acute injury on rat lung tissue and affected the respiratory function, but this effect was normally reversible.

关 键 词：经鼻滴入 油酸 博来霉素 支气管肺泡灌洗液 呼吸功能 

分 类 号：R965.3[医药卫生—药理学]