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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 effects of Qidan granules and tetrandrine on the treatment of fibrosis in rats with pneumoconiosis and its effect on the transforming growth factor β 1 (TGF-β 1) signaling pathway. Methods Forty male Wistar rats were randomly divided into control group, model group, Qidan granules treatment group (Qiandan group) and tetrandrine treatment group (Hanjia group), with 10 rats in each group. The control group was given tracheal injection of normal saline (1 ml), and the rest of the groups were modeled with tracheal injection of dust (50 mg/body). In the Qidan group and the Hanjia group, Gandan granules (3125 mg/kg) and tetrandrine (22 mg/kg) were infused from the 30th day after modeling, and the other groups were infused with an equal volume of normal saline. Weekly dosing for 6 days, for a total of 3 months, the remaining groups were given weekly for 7 days and administered for 4 months; all rats were sacrificed after 5 months and the lung coefficient was calculated; Hydroxyproline content was determined by enzyme-linked immunosorbent assay (ELISA). The expression of TGF-β_1 in bronchoalveolar lavage fluid was measured. The expression of TGF-β_1 and Smad3 in lung tissue was measured by immunohistochemistry (SABC method). Transcription factor Smad7 protein expression; Observe the pathological changes of lung tissue and kidney. Results The lung tissues of the model group mainly consisted of grade III-IV axillary nodules. The lung tissues of the Hudan group and the Hanjia group mainly consisted of grade II axillary nodules. The lung coefficients of the Hudan group and the Hanjia group were as follows: Acid content, bronchoalveolar lavage fluid, lung tissue TGF-β_1 and transcription factor Smad3 protein expression in lung tissue were lower than the model group, the difference was statistically significant (P<0.05); Qidan group, Hanjia group lung The protein expressions of transcription factor Smad7 in tissues were (169.5±4.88) and (169.55±4.73) higher than those in the model group, and the difference was statistically significant (P<0.05). The pathological changes of kidney injury occurred in the rats of the Hanjia group. Conclusion Both Qidan granules and tetrandrine can promote the expression of transcription factor Smad7 protein, inhibit the expression of transcription factors Smad3 protein and TGF-β_1 protein, and inhibit the progression of psoriasis fibrosis. Qidan granules have no nephrotoxicity.