Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Biomed Pharmacother. 2017 Nov;95:1799-1808. doi: 10.1016/j.biopha.2017.09.091. Epub 2017 Oct 6.
The aim of our study is to investigate the protective effect of apigenin and the role of the JAK2/STAT3 signaling pathway in renal ischemia/reperfusion injury (IRI) in rats. For in vivo experiments, rat kidneys were subjected to 45min of ischemia, followed by 24h of reperfusion. The kidneys were pretreated for 24h with apigenin (4mg/kg) intraperitoneally in the absence or presence of the JAK2 kinase-specific inhibitor AZD1480 (30mg/kg). The serum creatinine and urea nitrogen levels were analyzed. Histologic examinations were evaluated. Expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 was detected by immunohistochemistry or western blot. For In vitro experiments, NRK-52E cells were exposed to I/R in the absence or presence of apigenin and JAK2 siRNA was used to explore JAK2/STAT3 activity. Cell viability, cell apoptosis and expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 were examined in NRK-52E culture after I/R. Consequently, apigenin conferred a renoprotective effect on the kidneys against IRI, as evidenced by decreased serum creatinine and urea nitrogen, mitigated renal histologic damage, improved NRK-52E cell viability and a decreased apoptotic index, including up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic proteins Bax and Caspase3. However, AZD1480 and JAK2 siRNA blocked the apigenin-mediated renoprotective effects by attenuating the JAK2/STAT3 signaling pathway as well as abolished the effect of anti-oxidative stress and anti-apoptosis of apigenin. Our study demonstrates that apigenin pretreatment can protect against renal IRI via the activation of the JAK2/STAT3 signaling pathway.
我们的研究旨在探讨芹菜素在大鼠肾缺血再灌注损伤（IRI）中的保护作用及其对 JAK2/STAT3 信号通路的作用。在体内实验中，大鼠肾脏缺血 45 分钟，再灌注 24 小时。在无或有 JAK2 激酶特异性抑制剂 AZD1480（30mg/kg）的情况下，腹腔内给予芹菜素（4mg/kg）预处理 24 小时。分析血清肌酐和尿素氮水平。进行组织学检查。通过免疫组化或 Western blot 检测 p-JAK2、p-STAT3、Bcl-2、Bax 和 Caspase-3 的表达。在体外实验中，NRK-52E 细胞在无或有芹菜素和 JAK2 siRNA 的情况下暴露于 I/R，以探讨 JAK2/STAT3 活性。在 I/R 后，在 NRK-52E 培养物中检查细胞活力、细胞凋亡以及 p-JAK2、p-STAT3、Bcl-2、Bax 和 Caspase-3 的表达。结果表明，芹菜素对肾脏IRI 具有保护作用，表现为血清肌酐和尿素氮降低，减轻肾脏组织学损伤，提高 NRK-52E 细胞活力，降低细胞凋亡指数，包括上调抗凋亡蛋白 Bcl-2 和下调促凋亡蛋白 Bax 和 Caspase3。然而，AZD1480 和 JAK2 siRNA 通过减弱 JAK2/STAT3 信号通路阻断了芹菜素介导的肾保护作用，并消除了芹菜素的抗氧化应激和抗凋亡作用。我们的研究表明，芹菜素预处理可以通过激活 JAK2/STAT3 信号通路来保护肾脏免受 IRI。
