PI3K/Akt/p53通路介导番茄红素拮抗壬基酚肾毒性

Lycopene protects kidney against nonylphenol-induced nephrotoxicity by regulating PI3K/Akt/p53 pathway

番茄红素(lycopene,LYC)是一种高效抗氧化剂,可抵抗多种毒物对机体的肾毒性。但LYC拮抗壬基酚(nonylphenol,NP)诱导小鼠肾损伤的作用机制尚未明确。本研究通过建立LYC干预小鼠NP染毒模型,研究LYC对NP致小鼠肾毒性的拮抗作用和Akt/p53通路参与此过程的机制。结果显示,经过LYC干预后NP染毒小鼠日增体质量显著升高(P<0.05);小鼠血清肾功指数和肾脏抗氧化酶活性显著升高(P<0.05)。此外,LYC干预后小鼠肾脏凋亡通路蛋白PI3K、p-Akt和Bcl-2表达水平显著升高(P<0.05),p53和Bax表达水平显著降低(P<0.05)。结果表明,LYC能增强肾脏抗氧化能力,激活Akt/p53通路,抑制肾脏细胞凋亡,拮抗NP诱导的小鼠肾脏损伤。

Lycopene(LYC)is a highly effective antioxidant,which can also resist the nephrotoxicity of a variety of poisons.However,the mechanisms of LYC in antagonizing nonylphenol-induced nephrotoxicity have not been studied.In this study,we established LYC intervention model of nonylphenol exposure in mice to study the antagonistic effect of LYC on NP induced nephrotoxicity in mice and the mechanism of Akt/p53 pathway involved in this process.The results showed that the daily weight gain of NP exposed mice increased significantly after LYC treatment(P<0.05);serum renal function index and renal antioxidant enzyme activity increased significantly(P<0.05).In addition,after LYC intervention,the expression levels of renal apoptosis pathway proteins PI3 K,p-Akt and Bcl-2 increased significantly(P<0.05),and the expression levels of p53 and Bax decreased significantly(P<0.05).The results showed that LYC enhanced renal antioxidant capacity,activated PI3 K/Akt/p53 pathway,inhibited renal cell apoptosis and antagonized NP-induced renal injury in mice.