汉防己甲素和乙酰半胱氨酸联合用药对实验性矽肺的疗效观察  

Study on the therapeutic effects of tetrandrine combined with N-acetylcysteine on experimental silicosis of rats

作　　者：肖芸[1] 夏海玲[1] 朱丽瑾[1] 李鲜峰 陈日萍[1] 尹先宏 蒋兆强[1] 冯玲芳[1] 陈均强[1] 余珉[1] 楼建林[1] 张幸[1] 

机构地区：[1]浙江省医学科学院,杭州310013 [2]浙江金华康恩贝生物制药有限公司

出　　处：《中华劳动卫生职业病杂志》2015年第7期519-522,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的比较汉防己甲素（TD）、N-乙酰半胱氨酸（NAC）单独和联合给药对大鼠矽肺的治疗效果。方法40只大鼠分为盐水对照组、矽肺模型组、TD治疗组（50mg／kg）、NAC治疗组（500mg／kg）、联合治疗组（TD50mg／kg＋NAC500mg／kg），非暴露法气管内灌注石英粉尘。染尘后第2天起给药，1次／d，67欠／周，第30天处死大鼠。计算各脏器系数，观察肺组织病理变化，测定肺组织羟脯氨酸（HYP），丙二醛（MDA），肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）含量。结果各治疗组淋巴结系数、联合治疗组肺系数明显低于矽肺模型组，差异有统计学意义（P〈0．05）。病理观察：盐水对照组肺组织结构完好，肺间质无异常；矽肺模型组见多数矽结节，以Ⅱ～Ⅲ级细胞纤维性结节为主；TD治疗组以Ⅰ级尘细胞性结节为主，NAC治疗组以Ⅰ-Ⅱ级矽结节为主，联合治疗组仅见极少数细胞性结节，未出现胶原纤维和肺间质纤维组织增生。TD治疗组和联合治疗组HYP含量明显低于矽肺模型组，而NAC治疗组无明显变化。TD、NA及联合治疗组肺组织中MDA含量分别为（18．80±2．94），（20．13±4．01），（17．05±3．52）nmol／ml，均低于矽肺模型组[（23．99±3．26）nmol／ml]。矽肺模型组肺组织中IL-6含量为[9．57±8．78]pg／ml，TD和NAC单独治疗后IL-6下降至[（9．22±9．65）、（81．63±5．72）]pg／ml；而联合用药组用药后，IL-6下降到（74．37±3．17）pg／ml。矽肺模型组肺组织中TNF-α仅含量为（59．05±4．48）pg／ml，TD和NAC单独治疗后TNF-α含量下降至（50．48±2．76）和（54．28±4．30）g/ml；联合用药组用药后，TNF-α含量下降至（49．10±4．98）g／ml。与TD、NAC单纯治疗组比较，联合治疗组HYP、MDA、IL-6、TNF—α含量下降更为明显。结论TD及NAC能减轻染尘大鼠肺组织纤维化程度，降低肺组织中MDA、TNF�Objective To compare the effects of oral treatment with tetrandrine （TD） and N-acetylcysteine （NAC） separately or jointly on silica-exposed rats. Methods 40 sprague-Dawly （SD） rats were randomly divided into normal saline group, quartz group, TD treatment group （50mg/kg）, NAC treatment group （500 mg/ kg） and combined treatment group （TD： 50mg/kg ±NAC： 500mg/kg）. Rats in normal saline group and other groups received intratracheal instillation of normal saline and quartz dust suspension respectively. Treatment groups were given TD, NAC separately or jointly via esophagus the next day after instillation, once a day and six times a week for 30 consecutive days. At the end of experiment, the pathological changes of lung tissues were evaluated by the methods of Foot, HE and Masson staining, the level of hydroxyproline （HYP）, malondjaldehyde （MDA）, tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in lung tissues were measured by alkaline hydrolysis method, the barbituric acid method and enzyme-linked immunosorbent assay （ELISA） respectively. Results Compared with the quartz group, lymph nodes/body coefficients in all treatment groups and lung/body coefficient in combined treatment group were significantly decreased （P〈0.05）. Pathology results showed that the normal saline group demonstrated no obvious evidence of lung damage. The quartz group lungs silicotie lesions focused on Ⅱ-Ⅲlevel, the TD treatment group was mainly with Ⅰ level, the NAC treatment group was mainly with Ⅰ- Ⅱ level, and the combined treatment group only showed little silicotic nodule, no obvious fibrosis. HYP content in TD treatment g：oup and combined treatment group were significantly lower than that in the quartz group （P〈0.05）, while it showed no obvious change in NAC treatment group. MDA content in lung tissues of each treatment group （TD treatment group, NAC treatment group and combined treatment group） were 18.80±2.94, 20.13±4.01 and 17.05 ±3.52 nmol/ml res

关 键 词：矽肺 汉防己甲素 N-乙酰半胱氨酸 联合用药 

分 类 号：R135.2[医药卫生—劳动卫生]