| 应勇,柳慧金.丹参提取物对脑外伤大鼠神经元SIRT1-FoxO-自噬通路的影响[J].浙江中西医结合杂志,2020,30(3): |
| 丹参提取物对脑外伤大鼠神经元SIRT1-FoxO-自噬通路的影响 |
| Effect of Salvia miltiorrhiza extract on SIRT1-FoxO-autophagy pathway in neurons of rats with brain injury |
| 投稿时间：2019-11-29 修订日期：2020-02-05 |
| DOI： |
| 中文关键词: 丹参提取物 大鼠 SIRT1-FoxO-自噬通路 脑外伤 |
| 英文关键词:Salvia miltiorrhiza extract Rat SIRT1-FoxO-autophagy pathway Brain trauma |
| 基金项目:浙江省中医药科学研究基金项目（2019ZB015） |
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| 中文摘要: |
| 目的：研究丹参提取物对脑外伤大鼠神经元SIRT1-FoxO-自噬通路的影响。方法：采用Feeney 法构建大鼠脑外伤模型,将SD 大鼠78只随机分成6组,即假手术组、模型组、丹参提取物处理组(A组0.75 ml /mg、B组1.5 ml /mg、C组3.0 ml /mg)和抑制剂组。假手术组和模型组腹腔注射生理盐水5 ml,丹参提取物处理组分别腹腔注射各5 ml丹参提取物溶液,抑制剂组先按照B组剂量给药同时按照5 mg /kg注射SIRT1抑制剂(EX-527)。通过尼氏染色观察大鼠右侧脑组织神经元损伤情况；免疫组织化学染色、RT-PCR、Weston-blot分别测定SIRT1和FoxO1的细胞阳性率、mRNA水平和蛋白表达水平。结果：与假手术组相比,模型组SIRT1和FoxO1的阳性细胞比例、mRNA和蛋白表达量均显著升高(P<0.05)；与模型组相比,抑制剂组SIRT1的阳性细胞比例、mRNA和蛋白表达量均显著降低(P<0.05),A、B两组SIRT1蛋白水平及C组SIRT1、FoxO1的阳性细胞比例、mRNA和蛋白表达量均显著升高(P<0.05)；与抑制剂组相比,B、C两组SIRT1阳性细胞比例、A、B和C三组的FoxO1阳性细胞比例、SIRT1、FoxO1的 mRNA和蛋白水平都显著升高(P<0.05)；与A组相比,B组FoxO1 mRNA和SIRT1蛋白表达量及C组SIRT1阳性细胞比例、SIRT1和FoxO1的mRNA和蛋白表达量均显著升高(P<0.05)；与B组相比,C组SIRT1和FoxO1 mRNA表达显著升高(P<0.05)。结论：丹参注射液处理能够明显促进脑外伤大鼠神经元SIRT1表达,增强SIRT1的去乙酰化活性,正向调节SIRT1-FoxO1-自噬通路发挥神经保护作用。 |
| 英文摘要: |
| Objective: To investigate the effect of Salvia miltiorrhiza extract on SIRT1-FoxO-autophagy pathway in neurons of rats with brain injury. Methods: A rat brain injury model was established by Feeney method. Seventy-eight Sprague-Dawley rats were randomly divided into six groups: sham operation group, model group, Salvia miltiorrhiza extract treatment groups (group A: 0.75 ml/mg, group B: 1.5 ml/mg, group C: 3.0 ml/mg) and inhibitor group. Sham-operation group and model group were intraperitoneally injected with 5 ml saline, and Salvia miltiorrhiza extract group was intraperitoneally injected with 5 ml Salvia miltiorrhiza extract solution, respectively. Inhibitor group was given 5 mg/kg of SIRT1 inhibitor (EX-527) at the same time as group B. Nissl staining was used to observe the damage of neurons in the tissue of rats’ right brain, immunohistochemical staining, RT-PCR and Weston-blot were used to determine the positive rates of SIRT1 and FoxO1 cells, the levels of their mRNA and protein expression. Results: Compared with the sham group, the ratio of SIRT1 and FoxO1 positive cells, mRNA and protein expressions in the model group were significantly increased (P<0.05); Compared with the model group, the ratio of SIRT1 positive cells, mRNA and protein expression levels were significantly reduced in the inhibitor group (P<0.05); The levels of SIRT1 protein in group A and B, the proportion of SIRT1 and FoxO1 positive cells the expression of mRNA and protein in group C were significantly increased (P < 0.05); Compared with the inhibitor group, the ratio of SIRT1 positive cells in the group B, C and the ratio of FoxO1 positive cells in the group A, B, C and the mRNA and protein levels of SIRT1, FoxO1 were significantly increased (P<0.05).Compared with group A, the expression levels of FoxO1 mRNA and SIRT1 protein in group B, the ratio of sirt1-positive cells and the expression levels of SIRT1 and FoxO1 mRNA and protein in group C were significantly increased (P<0.05).Compared with group B, SIRT1 and FoxO1 mRNA expressions were significantly increased in group C (P<0.05). Conclusions: Salvia miltiorrhiza injection can significantly promote the expression of SIRT1 in neurons of rats with brain injury, enhance the deacetylation activity of SIRT1, and positively regulate the SIRT1-FoxO1-autophagy pathway to play a neuroprotective role. |
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