摘要
目的探讨芪丹颗粒剂与汉防己甲素治疗大鼠矽肺纤维化的疗效及其对转化生长因子β_1(TGF-β_1)信号传导通路的影响。方法将40只雄性Wistar大鼠随机分为对照组、模型组、芪丹颗粒剂治疗组(芪丹组)、汉防己甲素治疗组(汉甲组),每组各10只。对照组给予生理盐水(1 ml)气管注入,其余各组采用气管注入染尘(50 mg/只)造模。芪丹组和汉甲组分别从造模后第30天灌注芪丹颗粒剂(3125 mg/kg)和汉防己甲素(22 mg/kg),其余各组灌注等体积生理盐水,汉甲组每周给药6 d,共给药3个月,其余各组每周给药7 d,给药4个月;5个月后处死全部大鼠,计算大鼠肺系数;用碱水解法测定羟脯氨酸含量,用酶联免疫吸附测定法(ELISA)测定肺泡灌洗液中TGF-β_1蛋白的表达,用免疫组化(SABC法)方法测定肺组织中TGF-β_1、转录因子Smad3、转录因子Smad7蛋白表达;观察肺组织及肾脏病理改变。结果模型组肺组织主要以Ⅲ-Ⅳ级矽结节为主,芪丹组及汉甲组肺组织主要以Ⅱ级矽结节为主;芪丹组、汉甲组的肺系数、羟脯氨酸含量、支气管肺泡灌洗液及肺组织中TGF-β_1和肺组织中转录因子Smad3的蛋白表达均低于模型组,差异有统计学意义(P<0.05);芪丹组、汉甲组肺组织中转录因子Smad7的蛋白表达(169.5±4.88)、(169.55±4.73)均高于模型组,差异有统计学意义(P<0.05);汉甲组大鼠出现肾损伤的病理改变。结论芪丹颗粒剂与汉防己甲素均可促进转录因子Smad7蛋白表达,抑制转录因子Smad3蛋白和TGF-β_1蛋白表达,抑制矽肺纤维化的进展,芪丹颗粒剂无肾毒性。
Objective To investigate the molecule mechanism of the anti-fibrotic effects of Chinese herbal drugs （Qidan granules） in rats. Methods The male rats were randomly divided into four experimental groups： normal group, model group, Qidan group, tetrandrine group. Every group had 10 rats. Normal group were treated with physiologic saline while others were treated with silicon dioxide （50 mg/rat） by intratracheal instillation to induce silicosis. On 30th day Qidan group and Tetrandrine group were treated with Qidan granules （3125 mg/kg） or treated with tetrandrine （22 mg/kg） respectively. All the rats were scarified after 5 months. Lung/body coefficient was measured. Content of hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-β1 in bronchoalveolar lavage fluid was examined by using enzyme-linked immunosorbent assay （ELISA）. The gene expressions of transforming growth factor-betal, transcrip- tion factor Smad3 and Smad7 in lung were analyzed by using immunohistochemical technique （SP） and the image analysis. Results Model group mainly had Grade Ⅲ- Ⅳ silicotic nodule while Qidan group and tetrandrine group had Grade Ⅱ silicotic nodule. In Qidan group and tetrandrine group, lung/body coefficient and content of hydroxyproline and expression of transforming growth factor-betal and Smad3 in lung and expression of transforming growth factor-β1 in bronchoalveolar lavage fluid were lower than those in model group （P〈 0.05）. Expression of Smad7 in lung was higher than model group （P〈0.05）. Injury of kidney occurred in tetrandrine group. Conclusion Qidan granules and tetrandrine could inhibit expression of both Smad7 and trans- forming growth factor-β1, and promote expression of Smad3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2007年第6期336-340,共5页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
国家自然科学基金(30472203)
