滋阴明目丸通过激活音猬因子信号通路对小鼠视网膜色素变性的改善作用  

Ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa by activating the sonic hedgehog factor signaling pathway

作　　者：曾梅艳 熊萌 宋厚盼 欧晨 符超君 彭清华[2] 秦裕辉 ZENG Mei-yan;XIONG Meng;SONG Hou-pan;OU Chen;FU Chao-jun;PENG Qing-hua;QIN Yu-hui(College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Key TCM Laboratory of Otorhinolaryngology,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中医学院,湖南长沙410208 [2]湖南中医药大学中医药防治眼耳鼻咽喉疾病湖南省重点实验室,湖南长沙410208

出　　处：《中成药》2024年第8期2551-2561,共11页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(82004427);湖南省自然科学基金项目(2023JJ40474)。

摘　　要：目的探究滋阴明目丸对小鼠视网膜色素变性(RP)的改善作用及其可能机制。方法将RP转基因小鼠(rd10)随机分为模型组、乐盯组(0.15 g/kg)和滋阴明目丸低、高剂量组(4.50、9.00 g/kg),以C57BL/6小鼠为正常组,每组12只。HE染色检测小鼠视网膜组织病理改变,视网膜电图(ERG)检测视功能,光学相干断层扫描(OCT)观察小鼠眼底表现并检测视网膜厚度,激光散斑血流技术检测小鼠视网膜血液灌注量,数字PCR检测Shh信号通路信号分子Shh、Ptc、Smo、Gli1、N-myc、Cyclin mRNA表达,免疫荧光染色检测Shh、Ptc、Smo、Gli1、N-myc、Cyclin蛋白表达。结果与正常组比较,模型小鼠眼底和视网膜组织均发生病理性改变,ERG a波和b波振幅降低(P<0.01),视网膜厚度减少(P<0.01),视网膜血液灌注量降低(P<0.01),视网膜Shh、Ptc、Smo、Gli1、N-myc、Cyclin mRNA和蛋白表达均降低(P<0.01)。与模型组比较,滋阴明目丸各剂量组和乐盯组小鼠眼底和视网膜组织病理性改变均得到改善,视网膜厚度增加(P<0.01),视网膜血流量升高(P<0.01),ERG a波和b波振幅增加(P<0.01),视网膜Shh、Ptc、Smo、Gli1、N-myc、Cyclin mRNA和蛋白表达均升高(P<0.01)。结论滋阴明目丸可增加视网膜厚度和血流量,改善眼底病理改变和视功能,呈现出较好的延缓RP的作用,其机制可能与激活Shh信号通路有关。AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P<0.01);decreased retinal thickness(P<0.01);decreased retinal blood perfusion(P<0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P<0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P<0.01);increased retinal blood flow(P<0.01);increased amplitudes of ERG a wave and b wave(P<0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P<0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

关 键 词：滋阴明目丸 视网膜色素变性 rd10 视功能 SHH信号通路 

分 类 号：R285.5[医药卫生—中药学]