山奈酚调节PI3K/Akt信号通路对亚硒酸盐致白内障大鼠晶状体组织损伤的影响  

Impact of kaempferol on lens tissue damage in rats with selenite-induced cataract by regulating PI3K/Akt signaling pathway

作　　者：李秋霞 王广谋 陈健[1] 王华[1] 段国平[1] LI Qiuxia;WANG Guangmou;CHEN Jian;WANG Hua;DUAN Guoping(Department of Ophthalmology,Hunan Provincial People's Hospital(the First Affiliated Hospital of Hunan Normal University),Changsha 410000,China;Department of Ophthalmology,Shuangfeng County Zouma Street Eye Clinic,Loudi 417700,China)

机构地区：[1]湖南省人民医院(湖南师范大学附属第一医院)眼科,湖南长沙410000 [2]双峰县走马街眼科诊疗中心眼科,湖南娄底417700

出　　处：《东南大学学报（医学版）》2023年第3期362-369,共8页Journal of Southeast University(Medical Science Edition)

基　　金：湖南创新型省份建设专项项目(2020SK2118)。

摘　　要：目的:研究山奈酚(KAE)通过调节磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路对亚硒酸盐致白内障大鼠晶状体组织损伤的影响。方法:亚硒酸盐诱导法建立白内障大鼠模型。将大鼠分为对照组(NC组),模型组(M组),KAE低剂量(KAE-L)、中剂量(KAE-M)、高剂量(KAE-H)组(5、25、50 mg·kg^(-1)),KAE高剂量+通路抑制剂LY294002(H+LY294002)组(1.5 mg·kg^(-1))。十字格法检测晶状体透明度;HE染色检测晶状体病理学变化;TUNEL检测晶状体上皮细胞凋亡;试剂盒检测血清丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平及晶状体中白介素-6(IL-6)、肿瘤坏死因子(TNF-α)水平;蛋白质印迹法检测凋亡蛋白(Bax)、半胱氨酸天冬氨酸蛋白酶(C-Caspase)-12、C-Caspase-3、p-PI3K、PI3K、p-Akt、Akt蛋白表达。结果:与NC组相比,M组大鼠晶状体浑浊程度高,出现上皮细胞减少等损伤,上皮细胞凋亡率,MDA、IL-6、TNF-α水平,Bax、C-Caspase-12、C-Caspase-3表达显著增高(P<0.05),SOD水平、GSH-PX水平、p-PI3K/PI3K、p-Akt/Akt显著下降(P<0.05)。与M组相比,KAE-M、H组大鼠晶状体透明度恢复,病变显著好转,上皮细胞凋亡率,MDA、IL-6、TNF-α水平,Bax、C-Caspase-12、C-Caspase-3表达显著下降(P<0.05),p-PI3K/PI3K、p-Akt/Akt值上调(P<0.05)。LY294002明显减弱了KAE激活PI3K/Akt信号通路对白内障大鼠晶状体的保护作用。结论:KAE可能通过激活PI3K/Akt信号通路,改善亚硒酸盐致白内障大鼠晶状体组织损伤。Objective:To study the impact of kaempferol(KAE)on lens tissue damage in selenite-induced cataract rats by regulating phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods:The rat model of cataract was established by selenite induction method.The rats were grouped into control group(NC group),model group(M group),KAE low dose(KAE-L)group,medium dose(KAE-M)group,high dose(KAE-H)group(5,25,50 mg·kg^(-1)),and KAE high dose+pathway inhibitor LY294002(H+LY294002)group(1.5 mg·kg^(-1)).The cross-grid method was applied to detect lens transparency;HE staining was used to detect lens pathological changes;TUNEL was applied to detect lens epithelial cell apoptosis;the kit was applied to detect levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-PX)in serum,and levels of interleukin-6(IL-6)and tumor necrosis factor(TNF-α)in the lens;Western blotting was applied to detect protein expressions of apoptosis protein(Bax),caspase(C-Caspase)-12,C-Caspase-3,p-PI3K,PI3K,p-Akt,and Akt.Results:Compared with the NC group,the lens opacity of the rats in the M group was higher,and epithelial cell reduction and other damage occurred,the epithelial cell apoptosis rate,the levels of MDA,IL-6,TNF-α,the protein expressions of Bax,C-Caspase-12,and C-Caspase-3 increased obviously(P<0.05),the levels of SOD and GSH-PX,and the ratios of p-PI3K/PI3K and p-Akt/Akt decreased obviously(P<0.05).Compared with the M group,the lens transparency of the KAE-M and H groups recovered,and the lesions were obviously improved,the epithelial cell apoptosis rate,the levels of MDA,IL-6,TNF-α,the protein expressions of Bax,C-Caspase-12,and C-Caspase-3 decreased obviously(P<0.05),the ratios of p-PI3K/PI3K and p-Akt/Akt were up-regulated(P<0.05).LY294002 obviously attenuated the protective effect of KAE-activated PI3K/Akt signaling pathway on the lens of cataract rats.Conclusion:KAE may improve lens tissue damage in rats with selenite-induced cataract by activating PI3K/Akt signaling pathway.

关 键 词：山奈酚 亚硒酸盐 白内障 晶状体 磷脂酰肌醇-3-激酶/蛋白激酶B通路 大鼠 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学] R776.1