虎杖苷调节JAK2/STAT3信号通路治疗大鼠激素性股骨头坏死的实验研究  

Regulation of JAK2/STAT3 signaling pathway by polydatin in the treatment of hormone-induced femoral head necrosis in rats

作　　者：杨祥军 王丛悦 徐西林[3] 胡海[1] 申意伟 张晓峰[1] YANG Xiang-jun;WANG Cong-yue;XU Xi-lin;HU Hai;SHEN Yi-wei;ZHANG Xiao-feng(The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150001,Heilongjiang,China;Harbin Hospital of Traditional Chinese Medicine,Harbin 150070,Heilongjiang,China;The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150030,Heilongjiang,China;The Fourth Affiliated Hospital of Tianjin University of Chinese Medicine,Tianjin 300451,China)

机构地区：[1]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001 [2]哈尔滨市中医医院,黑龙江哈尔滨150070 [3]黑龙江中医药大学附属第三医院,黑龙江哈尔滨150030 [4]天津中医药大学第四附属医院,天津300451

出　　处：《中国骨伤》2025年第2期195-203,共9页China Journal of Orthopaedics and Traumatology

基　　金：黑龙江省中医药科研项目(编号:2023327)。

摘　　要：目的:探讨虎杖苷对大鼠激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)的治疗效果及其通过调节Janus激酶2/信号转导和转录激活因子3信号通路(janus kinase 2/signal transducer and activator of transcription 3 signaling pathway,JAK2/STAT3)影响骨组织保护的潜在机制。方法:5周雄性SD大鼠50只随机分为对照组、模型组、虎杖苷低剂量组(虎杖苷-L)、虎杖苷高剂量组(虎杖苷-H)及虎杖苷-H+Colivelin(JAK2/STAT3通路激活剂)组,每组10只。通过脂多糖和醋酸泼尼松龙诱导SONFH模型。治疗组在模型组基础上每日分别灌胃给予虎杖苷-L 10 mg·kg^(-1),虎杖苷-H 20 mg·kg^(-1),虎杖苷-H+Colivelin组腹腔注射Colivelin 1 mg·kg^(-1),对照组和模型组给予等体积生理盐水,持续6周。观察指标包括血清钙(calcium,Ca)、血清磷(phosphorus,P)、碱性磷酸酶(alkaline phosphatase,ALP)及转化生长因子β1(transforming growth factorβ1,TGF-β1)水平,micro-CT扫描,苏木精-伊红染色及Western blot检测JAK2/STAT3信号通路和成骨分化标志基因Runt相关转录因子2(runt-related transcription factor 2,Runx2)、骨形态发生蛋白2(bone morphogenetic protein 2,BMP2)、骨桥蛋白(osteopontin,OPN)蛋白表达。结果:与模型组相比,虎杖苷-L和虎杖苷-H组大鼠骨小梁面积百分比显著提升,空骨陷窝率显著下降(P<0.05)。Micro-CT分析表明,虎杖苷处理组骨体积分数、骨小梁数量和厚度增加,骨小梁分离度降低(P<0.05)。血清生化指标检测发现,虎杖苷-L和虎杖苷-H组大鼠血清Ca、P浓度恢复,碱性磷酸酶水平降低,转化生长因子β1水平升高(P<0.05)。Western blot分析显示,虎杖苷显著抑制了模型组中JAK2/STAT3信号通路的激活,同时促进了Runx2、BMP2、OPN等成骨分化标志基因的表达(P<0.05)。与虎杖苷-H组相比,虎杖苷-H+Colivelin组的这些改善效果有所减弱,显示JAK2/STAT3信号通路在虎杖苷作用中的重要性。结论:虎杖苷通Objective To explore the therapeutic effect of polygonum cuspidatum glycoside on steroid-induced osteonecrosis of the femoral head(SONFH)in rats and its potential mechanism of protecting bone tissue by regulating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway(JAK2/STAT3).Methods Fifty male SD rats were randomly divided into control group,model group,low-dose polygonum cuspidatum glycoside group(polygonum cuspidatum glycoside-L),high-dose polygonum cuspidatum glycoside group(polygonum cuspidatum glycoside-H),and polygonum cuspidatum glycoside-H+Colivelin(JAK2/STAT3 pathway activator)group.SONFH model was induced by lipopolysaccharide and dexamethasone.The treatment groups were given polygonum cuspidatum glycoside orally polygonum cuspidatum glycoside-L 10 mg·kg^(-1),polygonum cuspidatum glycoside-H 20 mg·kg^(-1),and the polygonum cuspidatum glycoside-H+Colivelin group was injected with Colivelin(1 mg·kg^(-1))intraperitoneally once a day,while the control and model groups were given an equal volume of saline for 6 weeks.The observed indicators included serum calcium(Ca),serum phosphorus(P),alkaline phosphatase,and transforming growth factorβ1(TGF-β1)levels,micro-CT scanning,hematoxylin-eosin staining,and Western blot detection of JAK2/STAT3 signaling pathway and osteogenic differentiation marker genes,including Runt-related transcription factor 2(Runx2),bone morphogenetic protein 2(BMP2),and osteopontin(OPN)protein expression.Results Compared with the model group,the trabecular bone area percentage in the polygonum cuspidatum glycoside-L and polygonum cuspidatum glycoside-H groups was significantly increased,and the empty lacunar rate was significantly decreased(P<0.05).Micro-CT analysis showed that the bone volume fraction,trabecular number,and thickness increased,and the trabecular separation decreased in the polygonum cuspidatum glycoside-treated groups(P<0.05).Serum biochemical tests found that the serum Ca and P concentrations in the polygonum cuspidatum glycoside-

关 键 词：虎杖苷 JAK2/STAT3信号通路 激素性股骨头坏死 成骨分化 骨组织保护 

分 类 号：R274.9[医药卫生—中西医结合]