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、BMPRⅠB、 BMPRⅡ、 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。

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.