[1]李正兴,田林,任童森,等.基于白介素6/Janus激酶2/信号转导与转录活化因子3信号通路探讨补肾活血方对去势大鼠骨质疏松症的影响[J].中国中医骨伤科杂志,2025,33(06):1-7.[doi:10.20085/j.cnki.issn1005-0205.250601]
　LI Zhengxing,TIAN Lin,REN Tongsen,et al.Effect of Kidney Tonifying and Blood Activating Formula on Osteoporosis in Castrated Rats Based on the IL-6/JAK2/STAT3 Signaling Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2025,33(06):1-7.[doi:10.20085/j.cnki.issn1005-0205.250601]
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基于白介素6/Janus激酶2/信号转导与转录活化因子3信号通路探讨补肾活血方对去势大鼠骨质疏松症的影响()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第33卷
期数:
2025年06期
页码:
1-7
栏目:
实验研究
出版日期:
2025-06-15

文章信息/Info

Title:
Effect of Kidney Tonifying and Blood Activating Formula on Osteoporosis in Castrated Rats Based on the IL-6/JAK2/STAT3 Signaling Pathway
文章编号:
1005-0205(2025)06-0001-07
作者:
李正兴1; 2; 田林1; 2; 任童森1; 2; 孙昭杰1; 2; 仲锋锋1; 2; 马勇1; 2; 3; 韩庭良1; 2△
1南京中医药大学附属盐城中医院(江苏 盐城,224001) 2盐城市中医院 3南京中医药大学中医学院(中西医结合学院)
Author(s):
LI Zhengxing1; 2; TIAN Lin1; 2; REN Tongsen1; 2; SUN Zhaojie1; 2; ZHONG Fengfeng1; 2; MA Yong1; 2; 3; HAN Tingliang1; 2△
1Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Yancheng 224001,Jiangsu China; 2Yancheng Hospital of Traditional Chinese Medicine,Yancheng 224001,Jiangsu China; 3College of Traditional Chinese Medicine(College of Integrated Traditional Chinese and Western Medicine),Nanjing University of Chinese Medicine,Nanjing 210029,China.
关键词:
补肾活血方;  绝经后骨质疏松症;  白介素6/Janus激酶2/信号转导与转录活化因子3信号通路;  炎症反应;  骨稳态
Keywords:
kidney tonifying and blood activating formula;  postmenopausal osteoporosis;  IL-6/JAK2/STAT3 signaling pathway;  inflammatory response;  bone homeostasis
分类号:
R-33
DOI:
10.20085/j.cnki.issn1005-0205.250601
文献标志码:
A
摘要:
目的:观察补肾活血方对绝经后骨质疏松症的干预作用,从白介素6(IL-6)/Janus激酶2(JAK2)/信号转导与转录活化因子3(STAT3)信号通路探讨其作用机制。方法:将SD大鼠随机分为正常组、模型组、阳性对照组、中药治疗组、抑制剂组、激活剂组,除正常组切除卵巢周围脂肪组织外,其余各组均采用切除大鼠双侧卵巢组织构建绝经后骨质疏松症动物模型。造模成功后给予药物干预12周,Micro-CT检测右侧股骨组织骨体积分数(BV/TV)、骨表面组织体积比值(BS/BV)、骨密度(BMD)及骨小梁宽度(Tb.Th)、骨小梁分离度(Tb.Sp)等微观结构静态参数。苏木精-伊红(HE)染色观察股骨组织骨小梁、破骨细胞及脂肪细胞的染色情况。ELISA检测大鼠血清中IL-6、TNF-α含量。Western Blot法检测大鼠右侧股骨组织中IL-6、JAK2、p-STAT3、STAT3蛋白的表达水平。RT-PCR检测IL-6、JAK2、STAT3 mRNA表达水平。结果:与正常组相比,模型组BMD、BV/TV、Tb.Th均明显降低,差异有统计学意义(P<0.05),BS/BV、Tb.Sp、破骨细胞及脂肪细胞均明显升高,差异有统计学意义(P<0.05),骨质疏松症模型造模成功。与模型组相比,阳性对照组、中药治疗组、抑制剂组BMD、BV/TV、Tb.Th均明显升高,差异有统计学意义(P<0.05),BS/BV、Tb.Sp、破骨细胞及脂肪细胞均明显降低,差异有统计学意义(P<0.05)。大鼠血清中IL-6、TNF-α含量显著下降,差异有统计学意义(P<0.05)。股骨组织中IL-6、JAK2、STAT3、p-STAT3蛋白表达显著下降,差异有统计学意义(P<0.05)。股骨组织中IL-6、JAK2、STAT3 mRNA表达显著下降,差异有统计学意义(P<0.05)。与中药治疗组相比,抑制剂组BMD、BV/TV、Tb.Th均明显升高,差异有统计学意义(P<0.05),BS/BV、Tb.Sp、破骨细胞及脂肪细胞均明显降低,差异有统计学意义(P<0.05)。大鼠血清中IL-6、TNF-α含量显著下降,差异有统计学意义(P<0.05)。而激活剂组中BMD、BV/TV、Tb.Th均明显降低,差异有统计学意义(P<0.05),BS/BV、Tb.Sp、破骨细胞及脂肪细胞均明显升高,差异有统计学意义(P<0.05)。大鼠血清中IL-6、TNF-α含量显著升高,差异有统计学意义(P<0.05)。结论:补肾活血方具有控制炎症反应、调节骨稳态平衡、改善骨密度、延缓骨质疏松症进程的作用,其作用机制可能与抑制IL-6/JAK2/STAT3信号通路有关。
Abstract:
Objective:To observe the intervention effect of kidney tonifying and blood activating formula on postmenopausal osteoporosis,and explore its mechanism of action from the IL-6/JAK2/STAT3 signaling pathway.Methods:SD rats were randomly divided into normal group,model group,positive control group,Chinese medicine treatment group,inhibitor group,and activator group.Except for the normal group,which had their ovarian adipose tissue removed,all other groups used bilateral ovarian tissue removal to construct postmenopausal osteoporosis animal models.After successful modeling,drug intervention was given for 12 weeks.Micro-CT was used to detect static microstructural parameters such as bone volume fraction(BV/TV),bone surface tissue volume ratio(BS/BV),bone mineral density(BMD),trabecular width(Tb.Th),and trabecular separation degree(Tb.Sp)in the right femur tissue.HE staining was used to observe the staining of bone trabeculae,osteoclasts,and adipocytes in femoral tissue.ELISA detection of IL-6 and TNF-α levels in rat serum.Western Blot was used to detect the expression levels of IL-6,JAK2,p-STAT3,and STAT3 proteins in the right femur tissue of rats.RT-PCR was used to detect the mRNA expression levels of IL-6,JAK2,and STAT3.Results:Compared with the normal group,the model group showed a significant decrease in BMD,BV/TV,and Tb.Th(P<0.05),while BS/BV,Tb.Sp,osteoclasts,and adipocytes were significantly increased(P<0.05),indicating the successful establishment of the osteoporosis model.Compared with the model group,the positive control group,Chinese medicine treatment group,and inhibitor group had significantly increased BMD,BV/TV,and Tb.Th(P<0.05),while BS/BV,Tb.Sp,osteoclasts,and adipocytes were significantly decreased(P<0.05).The levels of IL-6 and TNF-α in rat serum significantly decreased(P<0.05).The protein expression of IL-6,JAK2,STAT3,and p-STAT3 in femoral tissue significantly decreased(P<0.05).The expression of IL-6,JAK2,and STAT3 mRNA in femoral tissue significantly decreased(P<0.05).Compared with the Chinese medicine treatment group,the inhibitor group showed significantly increased BMD,BV/TV,Tb.Th(P<0.05),while BS/BV,Tb.SP,osteoclasts,and adipocytes were significantly decreased(P<0.05).The levels of IL-6 and TNF-α in rat serum significantly decreased(P<0.05).In the activator group,BMD,BV/TV,Tb.Th were significantly reduced(P<0.05),while BS/BV,Tb.SP,osteoclasts,and adipocytes were significantly increased(P<0.05).The levels of IL-6 and TNF-α in rat serum were significantly increased(P<0.05).Conclusion:The kidney tonifying and blood activating formula has the effects of controlling inflammatory response,regulating bone homeostasis balance,improving bone density,and delaying the process of osteoporosis.Its mechanism of action may be related to the inhibition of the IL-6/JAK2/STAT3 signaling pathway.

参考文献/References:

[1] WALKER M D,SHANE E.Postmenopausal osteoporosis[J].N Engl J Med,2023,389(21):1979-1991.
[2] ZHANG X,WANG Z,ZHANG D,et al.The prevalence and treatment rate trends of osteoporosis in postmenopausal women[J].PLoS One,2023,18(9):e290289.
[3] XIAO P L,CUI A Y,HSU C J,et al.Global,regional prevalence,and risk factors of osteoporosis according to the World Health Organization diagnostic criteria:a systematic review and meta-analysis[J].Osteoporos Int,2022,33(10):2137-2153.
[4] OU Y W,LAI C C,TSOU M T,et al.Development of machine learning models for prediction of osteoporosis from clinical health examination data[J].Int J Environ Res Public Health,2021,18(14):7635.
[5] XIAO W,SHEN Y,XU Y.LOX(G473A)induces the formation of osteoclasts in RAW264.7 cells via IL-6/JAK2/STAT3 signaling[J].Exp Cell Res,2021,409(1):112890.
[6] 马铭,任汉强.IL-37通过调控M-CSF和抑制IL-6/JAK2/STAT3抑制骨质疏松的机制研究[J].中国免疫学杂志,2017,33(10):1552-1556.
[7] 李正兴,韩庭良,尹佩玉,等.补肾活血方联合PKP术治疗骨质疏松性椎体骨折的临床疗效[J].内蒙古中医药,2020,39(10):16-18.
[8] 韩庭良,王国军,尹佩玉,等.PKP联合补肾活血方治疗骨质疏松椎体压缩骨折的临床研究[J].中国中医骨伤科杂志,2016,24(10):35-39.
[9] MENG J,ZHANG W,WANG C,et al.Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity[J].Biochem Pharmacol,2020,171:113715.
[10] MA Z,BAI L.The anti-inflammatory effect of Z-ligustilide in experimental ovariectomized osteopenic rats[J].Inflammation,2012,35(6):1793-1797.
[11] 李新春,胡万钧,甘发荣,等.杜仲-续断药对通过调控铁死亡途径对去卵巢骨质疏松症大鼠的保护作用及机制研究[J].中华中医药学刊,2023,41(9):103-106.
[12] OH Y C,JEONG Y H,CHO W K,et al.Inhibitory effects of epimedium herb on the inflammatory response in vitro and in vivo[J].Am J Chin Med,2015,43(5):953-968.
[13] WU W,FU J,GU Y,et al.JAK2/STAT3 regulates estrogen-related senescence of bone marrow stem cells[J].J Endocrinol,2020,245(1):141-153.
[14] GINTZLER A R,STORMAN E M,LIU N J.Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms[J].Vitam Horm,2019,111:227-246.
[15] CLINE-SMITH A,AXELBAUM A,SHASHKOVA E,et al.Ovariectomy activates chronic low-grade inflammation mediated by memory t cells,which promotes osteoporosis in mice[J].J Bone Miner Res,2020,35(6):1174-1187.
[16] HUANG X,NI B,LI Q,et al.Association between postmenopausal osteoporosis and IL-6,TNF-α:a systematic review and a meta-analysis[J].Comb Chem High Throughput Screen,2024,27(15):2260-2266.
[17] KAUR S,BANSAL Y,KUMAR R,et al.A panoramic review of IL-6:structure,pathophysiological roles and inhibitors[J].Bioorg Med Chem,2020,28(5):115327.
[18] 谭张奎,向楠,张妍,等.基于IL-6/JAK2/STAT3通路探讨补肾化痰方改善去势大鼠骨丢失的作用机制[J].中草药,2021,52(16):4904-4912.
[19] LIU J,XIE X,QIN K,et al.Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL-6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro[J].Immun Inflamm Dis,2022,10(11):e721.
[20] 沈锦涛,华茂奇,张北,等.由IL-10/JAK2/STAT3通路探讨养血柔筋方对兔膝骨关节炎软骨损伤的研究[J].中国骨质疏松杂志,2023,29(6):796-801.

备注/Memo

备注/Memo:
基金项目:江苏省卫生健康委员会科研项目(Z2023033)
盐城市科技局指令性项目(YCBK2023046)
盐城市卫生健康委员会重点项目(YK2023015)
△通信作者 E-mail:2017172134@qq.com
更新日期/Last Update: 2025-06-15