基于BMP2/Smad信号通路探讨电针对实验性近视豚鼠巩膜重塑的影响OA
Electroacupuncture on scleral remodeling in guinea pigs with experimental myopia based on the BMP/Smad signaling pathway
目的:基于骨形态发生蛋白-2(BMP2)/Smad 信号通路探讨电针对实验性近视豚鼠巩膜重塑的影响. 方法:本研究采用随机分配法将 80 只 2 周龄豚鼠划分为四组:正常对照(NC)组、负透镜诱导型近视(LIM)组、电针干预(EA)组和假穴(SHAM)组,每组 20 只.LIM 组、SHAM 组和 EA 组豚鼠右眼均配戴-6.00 D 透镜诱导近视;同时EA 组在太阳穴和合谷穴给予电针刺激;SHAM 组在双臀两侧远离传统经络区域给予电针刺激;正常组不做任何处理.检影验光检测屈光度,A 超检测眼轴长度,苏木精-伊红(HE)染色观察巩膜组织结构变化,实时荧光定量 PCR(qPCR)和蛋白免疫印迹法(WB)检测各组豚鼠巩膜中 BMP2/Smad 信号通路相关分子在 mRNA 和蛋白质水平的表达情况. 结果:造模2、4 wk 后,与 NC 组相比,LIM 组近视屈光度与眼轴长度均增加(均 P<0.05);与 LIM 组相比,EA 组近视屈光度和眼轴长度均降低(均 P<0.05).HE 染色显示LIM 组巩膜后极部变薄,胶原纤维排列疏松、紊乱;与 LIM组相比,EA 组巩膜后极部厚度增加,胶原纤维排列较紧密、有序.qPCR 和 WB 检测结果显示,在 mRNA 和蛋白质相对表达水平中,与 NC 组相比,LIM 组Ⅰ型胶原蛋白(Collagen Ⅰ)、BMP2、骨形态发生蛋白 ⅠA 型受体(BMPRⅠA)、骨形态发生蛋白ⅠB 型受体(BMPRⅠB)、骨形态发生蛋白Ⅱ型受体(BMPRⅡ)、Smad 家族成员1(Smad1)、Smad 家族成员 5(Smad5)、Smad 家族成员9(Smad9)、Smad 家族成员 4(Smad4)、组织金属蛋白酶抑制剂-2(TIMP-2)表达均显著下降,基质金属蛋白酶-2(MMP-2)、α-平滑肌肌动蛋白(α-SMA)表达均显著升高;与 LIM 组相比,EA 组 Collagen Ⅰ、BMP2、BMPRⅠA、BMPR Ⅰ B、BMPR Ⅱ、Smad1、Smad5、Smad9、Smad4、TIMP-2表达均显著升高,MMP-2、α-SMA 表达均显著下降. 结论:电针可通过调节实验性近视豚鼠巩膜 BMP2/Smad信号通路相关分子表达水平改善巩膜重塑和组织形态改变,抑制眼轴增长,从而延缓近视发生发展.
•AIM:To investigate the effects of electroacupuncture on scleral remodeling in guinea pigs with experimental myopia based on bone morphogenetic protein 2(BMP2)/Smad signaling pathway. •METHODS:A total of 80 two-week-old healthy guinea pigs were randomly divided into four groups:normal control(NC)group,lens-induced myopia(LIM)group,electroacupuncture(EA)group,and shame electroacupuncture(SHAM)group,with 20 guinea pigs in each group.The right eyes of guinea pigs in the LIM,SHAM,and EA groups had covered with -6.00 D lens to induce myopia.The EA group received electroacupuncture stimulation at the Taiyang and Hegu acupoints,while the SHAM group underwent stimulation at bilateral gluteal non-meridian areas.No intervention was performed on the NC group.Retinoscopy was used to measure the refractive error,and A-scan ultrasonography was used to measure the axial length.The changes in scleral structure were observed using hematoxylin-eosin(HE)staining.Real - time fluorescent quantitative polymerase chain reaction(qPCR)and Western blot(WB)were used to detect the mRNA and protein expression levels of BMP2/Smad signaling pathway-related molecules in the sclera of guinea pigs in each group. •RESULTS:After modeling for 2 and 4 wk,compared with the NC group,the degree of myopia and the axial length were increased in the LIM group(both P<0.05);compared with the LIM group,the degree of myopia and the axial length were decreased in the EA group(both P<0.05).HE staining showed thinned posterior scleral thickness in the LIM group,with a loose and disordered arrangement of collagen fibers.Compared with the LIM group,the posterior scleral thickness in EA group was increased and the collagen fibers were arranged relatively tightly and regularly.qPCR and WB results showed that,at both mRNA and protein relative expression levels,compared with the NC group,the LIM group exhibited significantly decreased expression of Collagen I,BMP2,bone morphogenetic protein type IA receptor(BMPRIA),bone morphogenetic protein type IB receptor(BMPRIB),bone morphogenetic protein type II receptor(BMPRII),Smad family member 1(Smad1),Smad family member 5(Smad5),Smad family member 9(Smad9),Smad family member 4(Smad4),and tissue inhibitor of metalloproteinase-2(TIMP-2),while the expression of matrix metalloproteinase-2(MMP-2)and alpha-smooth muscle actin(α - SMA)was significantly increased.Compared with the LIM group,the EA group showed significantly increased expression of Collagen I,BMP2,BMPRIA,BMPRIB,BMPRII,Smad1,Smad5,Smad9,Smad4,and TIMP - 2,and significantly decreased expression of MMP-2 and α-SMA. •CONCLUSION:Electroacupuncture can improve scleral remodeling and histomorphological changes,and inhibit axial elongation by regulating the expression levels of molecules related to the BMP2/Smad signaling pathway in the sclera of guinea pigs with experimental myopia,thereby delaying the onset and progression of myopia.
王普博;刘一洁;郝琪;毕宏生;吴秋欣;卢秀珍
(250014)中国山东省济南市,山东中医药大学(250014)中国山东省济南市,山东中医药大学(250014)中国山东省济南市,山东中医药大学(250002)中国山东省济南市,山东中医药大学附属眼科医院山东省眼病防治研究院 山东省中西医结合眼病防治重点实验室 山东省高校中西医结合眼病防治技术(强化)重点实验室(250002)中国山东省济南市,山东中医药大学附属眼科医院山东省眼病防治研究院 山东省中西医结合眼病防治重点实验室 山东省高校中西医结合眼病防治技术(强化)重点实验室(250002)中国山东省济南市,山东中医药大学附属眼科医院山东省眼病防治研究院 山东省中西医结合眼病防治重点实验室 山东省高校中西医结合眼病防治技术(强化)重点实验室
骨形态发生蛋白-2(BMP2)/Smad信号通路电针近视巩膜重塑
bone morphogenetic protein 2(BMP2)/Smad signaling pathwayelectroacupuncturemyopiascleral remodeling
《国际眼科杂志》 2026 (6)
940-949,10
国家自然科学基金项目(No.82104937)山东省医药卫生科技项目(No.202407021329)山东省中医药科技项目(No.M-2023010)山东省自然科学基金项目(No.ZR2024MH057) National Natural Science Foundation of China(No.82104937)Shandong Provincial Medical and Health Science and Technology Development Plan(No.202407021329)the Program of Traditional Chinese Medicine Science and Technology Project of Shandong Province(No.M-2023010)Natural Science Foundation of Shandong Province(No.ZR2024MH057)
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