Resveratrol inhibits TNF-α-induced inflammation to protect against renal ischemia/reperfusion injury in diabetic rats

Abstract Purpose To examine effects of resveratrol on renal ischemia/ reperfusion injury (I/R) in a streptozotocin (STZ)-induced diabetic rat model. Methods Twenty-four male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: Sham group, I/R group and Resveratrol group (n=8). Resveratrol (RSV) was administered at a dose of 10 mg.kg-1.d-1 fourteen days prior to suffering from I/R. Renal function, histology, SOD, MDA, TUNEL assay and expression of TNF-α, IL-1β, NF-κB-P65, COX-2 and Caspase3, Bcl2 and Bax were analyzed. Results Administration of RSV significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen and MDA; in the other hand, it significantly increased the serum levels of SOD. The protective effect of RSV was also reflected on histologic evaluation. RSV reduced the number of apoptotic cells as determined by TUNEL assay. RSV significantly reduced the protein expression of TNF-α, IL-1β, NF-κB-P65, COX-2 and Caspase3, and Bax. Meanwhile, RSV significantly increased the protein expression of Bcl2. Conclusion RSV attenuated I/R-induced renal injury in diabetic rats through the modulation of oxidative stress and TNF-α-stimulated inflammation.

摘要
研究目的：探讨白藜芦醇（Resveratrol, RSV）对链脲佐菌素（Streptozotocin, STZ）诱导的糖尿病大鼠模型中肾缺血再灌注损伤（Ischemia/Reperfusion Injury, I/R）的影响。

方法：将24只雄性斯普拉格-道利（Sprague Dawley）大鼠经链脲佐菌素注射构建糖尿病模型，随机分为假手术组、缺血再灌注组及白藜芦醇组，每组8只。于缺血再灌注造模前14天给予白藜芦醇干预，剂量为10 mg·kg⁻¹·d⁻¹。随后检测各组大鼠肾功能、组织病理学指标、超氧化物歧化酶（SOD）活性、丙二醛（MDA）水平、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定（TUNEL assay）结果，以及肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、核因子κB-P65（NF-κB-P65）、环氧合酶-2（COX-2）、半胱氨酸天冬氨酸蛋白酶3（Caspase3）、B细胞淋巴瘤2（Bcl2）及Bcl2相关X蛋白（Bax）的蛋白表达水平。

结果：白藜芦醇干预可显著降低肾功能损伤标志物（肌酐、血尿素氮）及血清丙二醛水平，同时显著升高血清超氧化物歧化酶活性；组织病理学评估亦印证了其肾脏保护作用。TUNEL染色结果显示，白藜芦醇可减少凋亡细胞数量。此外，白藜芦醇可显著下调TNF-α、IL-1β、NF-κB-P65、COX-2、Caspase3及Bax的蛋白表达，同时上调Bcl2的蛋白表达。

结论：白藜芦醇可通过调节氧化应激及肿瘤坏死因子-α介导的炎症反应，减轻糖尿病大鼠缺血再灌注诱导的肾损伤。