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[目的]观察槲皮素(quercetin)对矽肺大鼠转化生长因子β1(transforming growth factor beta 1,TGF-β1)信号转导通路的调节作用。[方法]将75只SPF(specific-pathogen-free)级Wistar雄性大鼠随机分为对照组、模型组、槲皮素治疗组,每组25只。模型组与槲皮素治疗组大鼠采用非暴露法气管内一次性注入二氧化硅(SiO2)悬液(250 mg/kg)复制动物矽肺模型。槲皮素治疗组自注射SiO2后每天腹腔注射含50 mg/kg槲皮素的生理盐水1.0 mL,对照组以同样方法注入等量生理盐水,共连续处理14 d。分别在注射SiO2后第3、7、14、21、28天处死动物。应用羟脯氨酸试剂盒检测肺组织中总胶原蛋白含量,免疫组织化学法检测肺组织TGF-β1表达,蛋白免疫印迹(Western blot)法检测TGF-β1直接底物p-Smad3/7蛋白表达情况。[结果]模型组肺组织中总胶原蛋白含量与同期对照组比较明显增加,分别是对照组的6.28、13.11、11.59倍(P<0.01)。槲皮素治疗组与模型组相比,总胶原蛋白含量明显下降,分别是同期模型组的43.05%、38.92%、37.40%(P<0.01)。槲皮素治疗组的TGF-β1阳性表达低于模型组,而明显高于对照组;各时间点与对照组比较,差异有统计学意义(P<0.01,P<0.05)。模型组大鼠肺组织中p-Smad3表达量高于对照组及槲皮素治疗组;各时间点比较,差异均有统计学意义(P<0.01)。槲皮素治疗组各时间点与相应模型组相比,p-Smad3表达减少,但仍高于相应对照组(P<0.01)。模型组大鼠肺组织中p-Smad7表达量低于对照组及槲皮素治疗组;各时间点比较,差异均有统计学意义(P<0.01)。槲皮素治疗组各时间点与对照组、模型组相比,p-Smad7表达量升高(P<0.01)。[结论]槲皮素通过减少Smad3蛋白表达,增加Smad7蛋白表达,抑制矽肺过程中胶原蛋白的产生。
[Objective] To observe the regulatory effect of quercetin on the signal transduction pathway of transforming growth factor β1 (TGF-β1) in silicosis rats. [Methods] Seventy-five male Wistar rats with specific-pathogen-free SPF were randomly divided into control group, model group and quercetin treatment group, with 25 rats in each group. Rats in the model group and the quercetin-treated group were intraperitoneally injected with silicon dioxide (SiO2) suspension (250 mg / kg) in a non-exposed way to replicate the silicosis model. In the quercetin treatment group, 1.0 mL normal saline containing 50 mg / kg quercetin was intraperitoneally injected after SiO2 injection, and the control group was injected with the same amount of normal saline in the same way for a total of 14 d. Animals were sacrificed on days 3, 7, 14, 21 and 28 after injection of SiO2 respectively. The content of total collagen in lung tissue was detected by hydroxyproline kit. The expression of TGF-β1 in lung tissue was detected by immunohistochemistry. The expression of p-Smad3 / 7 protein, a direct substrate of TGF-β1, was detected by Western blot Happening. [Result] The content of total collagen in the lung tissue of the model group was significantly increased compared with that of the control group at the same time (6.28, 13.11 and 11.59 times respectively) (P <0.01). Compared with the model group, the content of total collagen in the quercetin treatment group was significantly decreased, which was 43.05%, 38.92% and 37.40% respectively (P <0.01) in the model group. The expression of TGF-β1 in quercetin-treated group was lower than that in model group, but significantly higher than that in control group (P <0.01, P <0.05). The expression of p-Smad3 in model group was higher than that in control group and quercetin treatment group at each time point (P <0.01). Compared with the corresponding model group, the expression of p-Smad3 in quercetin treatment group at each time point decreased, but still higher than that in the corresponding control group (P <0.01). The expression of p-Smad7 in the lung tissue of the model group was lower than that of the control group and quercetin treatment group at each time point, the differences were statistically significant (P <0.01). Compared with the control group and model group, the expression of p-Smad7 increased in quercetin-treated group at each time point (P <0.01). [Conclusion] Quercetin can inhibit the production of collagen during the process of silicosis by decreasing the expression of Smad3, increasing the expression of Smad7.