丁苯酞对肾间质纤维化的干预作用及机制研究
发布时间：2019-08-20 09:14
【摘要】：目的探讨丁苯酞的肾保护机制及核因子E2相关因子2(Nrf2)-抗氧化还原反应元件(Nrf2-ARE)通路在肾间质纤维化中的作用。方法清洁级CD-1小鼠分为4组:假手术组、模型组、治疗组、阳性对照组。假手术组、模型组均给予等量生理盐水灌胃。治疗组、阳性对照组分别给予丁苯酞、贝那普利灌胃。将各组小鼠分别于术后第3、7、14天处死,取梗阻侧肾组织,通过免疫组织化学染色、RT-PCR等实验手段检测肾组织Ⅰ型胶原蛋白、Nrf2及γ-GCS蛋白及mRNA的表达水平。并将Nrf2与γ-GCS及Ⅰ型胶原蛋白与γ-GCS进行相关性分析。结果免疫组织化学及RT-PCR结果均显示模型组Ⅰ型胶原蛋白mRNA及蛋白较假手术组有明显升高,并且随着梗阻时间的延长表达逐渐增多。治疗组及阳性对照组小鼠在各时间点较模型组表达显著减少。动态观察Nrf2mRNA的表达,结果显示:与同期假手术组相比,术后3、7、14d模型组小鼠肾组织中Nrf2、r-GCS、I型胶原蛋白mRNA表达均增加,给予丁苯酞干预后,Nrf2mRNA在7、14d时治疗组与模型组比较表达均显著增加(P0.05),治疗组Nrf2在各时间点表达均强于阳性对照组(P0.05)。RT-PCR学检测γ-GCS mRNA变化趋势同于Nrf2,其肾保护效应随时间延长呈增强趋势。相关性分析显示:Nrf2与γ-GCS呈正相关(r=0.950,P0.05),γ-GCS与Ⅰ型胶原蛋白呈负相关(r=-0.629,P0.05)。结论丁苯酞有抗肾间质纤维化作用,机制可能与激活Nrf2-ARE信号通路,提高肾间质中Nrf2、抗氧化酶r-GCS活性水平有关。
[Abstract]:Objective to investigate the renal protective mechanism of butylphthalide and the role of nuclear factor E2 related factor 2 (Nrf2)-antioxidant reduction element (Nrf2-ARE) pathway in renal interstitial fibrosis. Methods Clean CD-1 mice were divided into 4 groups: false operation group, model group, treatment group and positive control group. In the pseudo-operation group and the model group, the same amount of saline was given intragastrically. In the treatment group and the positive control group, butylphthalide and benazepril were given intragastrically. The mice in each group were killed on the 3rd, 7th and 14th day after operation. The renal tissue of the obstructive side was taken. The expression of type I collagen, Nrf2, gamma-GCS protein and mRNA in renal tissue were detected by immunohistochemical staining and RT-PCR. The correlation between Nrf2 and gamma-GCS and type I collagen and gamma-GCS was analyzed. Results Immunohistochemical and RT-PCR results showed that the expression of type I collagen mRNA and protein in the model group was significantly higher than that in the false operation group, and increased gradually with the prolongation of obstruction time. The expression of mice in treatment group and positive control group was significantly lower than that in model group at each time point. The expression of Nrf2mRNA was observed dynamically. The results showed that the expression of Nrf2,r-GCS, type I collagen mRNA in renal tissue of model group was increased at 3, 7 and 14 days after operation, and the expression of Nrf2mRNA in treatment group was significantly higher than that in model group at 7 and 14 days after butylphthalide intervention (P 0.05). The expression of Nrf2 in the treatment group was stronger than that in the positive control group at all time points (P 0.05). The change trend of 纬-GCS mRNA detected by RT-PCR was the same as the renal protective effect of Nrf2, increased with the prolongation of time. Correlation analysis showed that Nrf2 was positively correlated with 纬-GCS (r 鈮，
本文编号：2528521
[Abstract]:Objective to investigate the renal protective mechanism of butylphthalide and the role of nuclear factor E2 related factor 2 (Nrf2)-antioxidant reduction element (Nrf2-ARE) pathway in renal interstitial fibrosis. Methods Clean CD-1 mice were divided into 4 groups: false operation group, model group, treatment group and positive control group. In the pseudo-operation group and the model group, the same amount of saline was given intragastrically. In the treatment group and the positive control group, butylphthalide and benazepril were given intragastrically. The mice in each group were killed on the 3rd, 7th and 14th day after operation. The renal tissue of the obstructive side was taken. The expression of type I collagen, Nrf2, gamma-GCS protein and mRNA in renal tissue were detected by immunohistochemical staining and RT-PCR. The correlation between Nrf2 and gamma-GCS and type I collagen and gamma-GCS was analyzed. Results Immunohistochemical and RT-PCR results showed that the expression of type I collagen mRNA and protein in the model group was significantly higher than that in the false operation group, and increased gradually with the prolongation of obstruction time. The expression of mice in treatment group and positive control group was significantly lower than that in model group at each time point. The expression of Nrf2mRNA was observed dynamically. The results showed that the expression of Nrf2,r-GCS, type I collagen mRNA in renal tissue of model group was increased at 3, 7 and 14 days after operation, and the expression of Nrf2mRNA in treatment group was significantly higher than that in model group at 7 and 14 days after butylphthalide intervention (P 0.05). The expression of Nrf2 in the treatment group was stronger than that in the positive control group at all time points (P 0.05). The change trend of 纬-GCS mRNA detected by RT-PCR was the same as the renal protective effect of Nrf2, increased with the prolongation of time. Correlation analysis showed that Nrf2 was positively correlated with 纬-GCS (r 鈮，
本文编号：2528521
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