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-东南大学学报医学版

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

单位：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]

分类号：R285.5; R-332; R776.1

出版年·卷·期（页码）：2023·42·第三期（362-369）

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.

参考文献：

[1] ANG M J,AFSHARI N A.Cataract and systemic disease: a review[J].Clin Exp Ophthalmol,2021,49(2):118-127.
[2] ŞEKEROGLU H T,UTINE G E.Congenital cataract and its genetics: the era of next-generation sequencing[J].Turk J Ophthalmol,2021,51(2):107-113.
[3] NEUHANN I,NEUHANN L,NEUHANN T.Die senile katarakt [age-related cataract][J].Klin Monbl Augenheilkd,2022,239(4):615-633.
[4] TSAI C F,WU J Y,HSU Y W.Protective effects of rosmarinic acid against selenite-induced cataract and oxidative damage in rats[J].Int J Med Sci,2019,16(5):729-740.
[5] REN B C,ZHANG Y F,LIU S S,et al.Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signalling pathways[J].J Cell Mol Med,2020,24(21):12355-12367.
[6] XIAN M,CAI J,ZHENG K,et al.Aloe-emodin prevents nerve injury and neuroinflammation caused by ischemic stroke via the PI3K/AKT/mTOR and NF-κB pathway[J].Food Funct,2021,12(17):8056-8067.
[7] JIN Y,ZHAI Z,JIA H,et al.Kaempferol attenuates diquat-induced oxidative damage and apoptosis in intestinal porcine epithelial cells[J].Food Funct,2021,12(15):6889-6899.
[8] XIAO Y,LIU L,ZHENG Y,et al.Kaempferol attenuates the effects of XIST/miR-130a/STAT3 on inflammation and extracellular matrix degradation in osteoarthritis[J].Future Med Chem,2021,13(17):1451-1464.
[9] FENG Z,WANG C,YUE J,et al.Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway[J].Pharm Biol,2021,59(1):1106-1116.
[10] ACHETE DE SOUZA G,DE MARQUI S V,MATIAS J N,et al.Effects of ginkgo biloba on diseases related to oxidative stress[J].Planta Med,2020,86(6):376-386.
[11] PATIL K K,MESHRAM R J,BARAGE S H,et al.Dietary flavonoids inhibit the glycation of lens proteins: implications in the management of diabetic cataract[J].3 Biotech,2019,9(2):47-62.
[12] PADMANABHA S,VALLIKANNAN B.Fatty acids influence the efficacy of lutein in the modulation of α-crystallin chaperone function: Evidence from selenite induced cataract rat model[J].Biochem Biophys Res Commun,2020,529(2):425-431.
[13] 梁玉雕,谭友果,张莎,等.山奈酚对慢性应激抑郁模型老年大鼠抑郁样行为的影响及机制研究[J].中国临床药理学杂志,2020,36(24):4028-4030.
[14] 陈忠仁,欧宗兴,王蕾,等.磷脂酰肌醇3激酶抑制剂对慢性阻塞性肺疾病大鼠肺功能及支气管平滑肌厚度的影响[J].中国临床药理学杂志,2020,36(23):3907-3909,3921.
[15] AHMAD A,AHSAN H.Biomarkers of inflammation and oxidative stress in ophthalmic disorders[J].J Immunoassay Immunochem,2020,41(3):257-271.
[16] SONG M S,SIM H J,KANG S,et al.Pharmacological inhibition of Kv3 on oxidative stress-induced cataract progression[J].Biochem Biophys Res Commun, 2020,533(4):1255-1261.
[17] RAN H,LIU H,WU P.Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway[J].Adv Clin Exp Med,2021,30(11):1195-1203.
[18] SRI-ISWARI R,DAFIP M,PURWANTOYO E.Malondialdehyde(MDA) production in atherosclerosis supplemented with steamed tomato[J].Pak J Biol Sci,2021,24(3):319-325.
[19] FENG H,WANG L,ZHANG G,et al.Oxidative stress activated by Keap-1/Nrf2 signaling pathway in pathogenesis of preeclampsia[J].Int J Clin Exp Pathol,2020,13(3):382-392.
[20] BAKHSHII S,KHEZRI S,AHANGARI R,et al.Protection of clozapine-induced oxidative stress and mitochondrial dysfunction by kaempferol in rat cardiomyocytes[J].Drug Dev Res,2021,82(6):835-843.
[21] SUN C,WANG T,WANG C,et al.The protective effect of kaempferol against ischemia/reperfusion injury through activating SIRT3 to inhibit oxidative stress[J].Braz J Cardiovasc Surg,2022,37(3):335-342.
[22] LEE J K,KANG S,WANG X,et al.HAP1 loss confers l-asparaginase resistance in ALL by downregulating the calpain-1-Bid-caspase-3/12 pathway[J].Blood, 2019,133(20):2222-2232.
[23] LI H,FANG H.Effect of microincisional cataract surgery on inflammatory indicators in tears and corneal endothelial cells in cataract patients[J].Am J Transl Res,2021,13(7):7705-7714.
[24] YAO L,YAN H.MiR-182 inhibits oxidative stress and epithelial cell apoptosis in lens of cataract rats through PI3K/Akt signaling pathway[J].Eur Rev Med Pharmacol Sci,2020,24(23):12001-12008.
[25] ZHAO N,SHI J,XU H,et al.Baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo[J].Bioengineered,2021,12(2):10187-10198.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录