白藜芦醇通过激活 HSP70 表达对尿毒症大鼠肾脏发挥保护作用。
Resveratrol Plays Protective Roles on Kidney of Uremic Rats via Activating HSP70 Expression.
机构信息
Department of Nephrology, Yantai Hospital of Traditional Chinese Medicine, Yantai, 264000 Shandong, China.
Department of Nephrology, Yantaishan Hospital, Yantai, 264000 Shandong, China.
出版信息
Biomed Res Int. 2020 Mar 23;2020:2126748. doi: 10.1155/2020/2126748. eCollection 2020.
OBJECTIVE
To investigate the protective effects of resveratrol on kidney of uremic rats and to explore whether the mechanism is associated with heat shock protein 70 (HSP70) expression.
METHODS
Sixty male Sprague Dawley rats were randomly separated into 5 groups, including sham group, uremic model group, and different doses of resveratrol group (5 mg/kg, 10 mg/kg, and 20 mg/kg). The serum creatinine (Cr) and urea nitrogen (BUN) levels were detected by Automatic Biochemical Analyzer (ABA). The pathological changes of renal tissues and the renal interstitial fibrosis were analyzed by hematoxylin-eosin (HE) and Masson, respectively. The expression of HSP70 protein in renal tissues was detected by immunohistochemistry. The expression of HSP70 and NF-B pathway-related proteins were detected by Western blot. To further validate the protective role of resveratrol through activating HSP70 in uremic rats, HSP70 activator (17-AAG) and HSP70 inhibitor group (MKT-077) were used.
RESULTS
In the model group, the levels of Cr and BUN in serum were significantly increased, and the renal interstitial collagen deposition was also obviously increased ( < 0.05). Compared with the model group, the levels of Cr and BUN in different doses of resveratrol groups were remarkably declined, and the renal interstitial collagen deposition was declined ( < 0.05). Resveratrol also significantly improved the renal tissue lesions when compared with the model group. In renal tissues, different doses of resveratrol treatment remarkably raised HSP70 and p-IB expression and also remarkably declined the level of p-P65 protein ( < 0.05). Meanwhile, the effect of 17-AAG was similar to 20 mg/kg resveratrol on NF-B pathway-related proteins expression. After the added MKT-077 in the resveratrol treatment group, the levels of HSP70 and p-IB in the renal tissue were remarkably declined; however, the levels of p-P65 protein was remarkably raised ( < 0.05).
CONCLUSION
Resveratrol played a protective role on the kidney of uremic rats through activating HSP70 expression.
目的
研究白藜芦醇对尿毒症大鼠肾脏的保护作用，并探讨其机制是否与热休克蛋白 70（HSP70）表达有关。
方法
60 只雄性 Sprague Dawley 大鼠随机分为 5 组，包括假手术组、尿毒症模型组和不同剂量白藜芦醇组（5mg/kg、10mg/kg 和 20mg/kg）。采用全自动生化分析仪（ABA）检测血清肌酐（Cr）和尿素氮（BUN）水平。苏木精-伊红（HE）和 Masson 分别分析肾组织的病理变化和肾间质纤维化。免疫组织化学法检测肾组织中 HSP70 蛋白的表达。Western blot 法检测 HSP70 和 NF-B 通路相关蛋白的表达。为了进一步通过激活尿毒症大鼠中的 HSP70 验证白藜芦醇的保护作用，使用 HSP70 激活剂（17-AAG）和 HSP70 抑制剂组（MKT-077）。
结果
在模型组中，血清中 Cr 和 BUN 的水平明显升高，肾间质胶原沉积也明显增加（ < 0.05）。与模型组相比，不同剂量白藜芦醇组的 Cr 和 BUN 水平显著下降，肾间质胶原沉积减少（ < 0.05）。与模型组相比，白藜芦醇组也明显改善了肾组织损伤。在肾组织中，不同剂量白藜芦醇处理显著提高 HSP70 和 p-IB 的表达，同时显著降低 p-P65 蛋白水平（ < 0.05）。同时，17-AAG 的作用与 20mg/kg 白藜芦醇对 NF-B 通路相关蛋白表达的作用相似。在加入 MKT-077 后，白藜芦醇治疗组肾组织中 HSP70 和 p-IB 的水平显著下降，而 p-P65 蛋白水平显著升高（ < 0.05）。
结论
白藜芦醇通过激活 HSP70 表达对尿毒症大鼠肾脏发挥保护作用。
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