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Effects of dipsacus prescription added with Rhizoma Drynariae on bone tissue and PI3K/Akt signaling pathway in rabbits with steriod-induced |
FU Zixiang WANG Fengming ZHAO Canbin BI Rongxiu LI Xiaoyang |
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Shandong Province, Jinan 250000, China
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Abstract Objective To observe the therapeutic effect and mechanism of dipsacus prescription added with Rhizoma Drynariae (DPRD) on steroid-induced avascular necrosis of the femoral head(SANFH) rabbits. Methods Twenty-four 2.5-3.0 kg normal grade 4-week-old healthy male New Zealand rabbits were randomly number table method divided into blank group, model group, DPRD low-dose group (group L), and DPRD high-dose group (group H), with six rabbits in each group. The model group, group L, and group H were injected with E. coli endotoxin combined with glucocorticoid for modeling, and MRI was performed six weeks later to evaluate the modeling results. After successful modeling, blank group, and model group were administrated with 5 ml/kg normal saline daily, while group L, and group H were administrated with 2.5 ml/kg and 5.0 ml/kg DPRD decoction, respectively. After six weeks of intervention, MRI was performed, then the animals were killed and the femoral head was removed. The expression levels of phosphatidylinositol 3 kinase (Pi3K), seronine/threonine protein kinase (Akt), phosphorylated protein kinase (P-Akt), human forkhead protein O1 (FOXO1), and vascular endothelial growth factor (VEGF) in the femoral head of rabbits in each group were detected by immunohistochemistry and Western blot. Results After six weeks of modeling, MRI showed that the femoral head of the model group, group L, and group H had collapsed and flattened symptoms, and linear or circular high signal shadow appeared in the femoral head. After six weeks of DPRD intervention, MRI showed that DPRD could effectively improve femoral head necrosis in model rabbits. Western blot and immunohistochemical detection results showed that, compared with blank group, the expression levels of PI3K, Akt, and P-Akt were significantly increased, while the expression level of FOXO1 was significantly decreased in model group (P<0.05). Compared with model group, the expression levels of PI3K, Akt, and p-Akt in group L and group H were significantly decreased, while the expression level of FOXO1 was significantly increased (P<0.05). Compared with group L, the expression levels of PI3K, P-Akt, and FOXO1 in group H were increased (P<0.05), but there was no statistical significance in the expression level of Akt between group L and group H (P>0.05). In addition, compared with blank group, the expression levels of Akt and P-Akt were increased, and the expression level of VEGF was decreased in model group (P<0.05). Compared with model group, the expression levels of Akt and P-Akt in group L and group H were decreased, and the expression levels of VEGF were increased (P<0.05). There were no significant differences in Akt, P-Akt, and VEGF between group L and group H (P>0.05). Conclusion By regulating PI3K/Akt pathway, DPRD increases the expression of FOXO1, hormone-induced necrosis of femoral head VEGF and reverses the effect of glucocorticoids.
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[1] Peng P,Nie Z,Sun F,et al. Glucocorticoids induce femoral head necrosis in rats through the ROS/JNK/c-Jun pathway [J]. FEBS Open Bio,2021,11(1):312-321.
[2] 孙懿,赵海燕,成杰,等.激素性股骨头坏死发生机制的研究进展[J].中国矫形外科杂志,2023,31(1):58-62.
[3] 王诗玮,李玉姝.糖皮质激素诱导骨坏死[J].中华骨质疏松和骨矿盐疾病杂志,2021,14(4):404-411.
[4] 韩杰,任国武,莫坚,等.补肾活血类中药复方干预激素性股骨头缺血性坏死的相关信号通路及作用靶点[J].中国组织工程研究,2022,26(11):1758-1764.
[5] 乌日莎娜,陈哓俊,沈莹姗,等.活血通络胶囊通过OPG/ RANKL/PDGF-BB通路对激素性股骨头坏死模型大鼠的干预作用[J].中药新药与临床药理,2022,33(4):433- 440.
[6] 辛鹏飞,柯梦楠,张海涛,等.活血化瘀中药治疗股骨头坏死共同作用机制的网络药理学数据[J].中国组织工程研究,2021,25(17):2727-2733.
[7] 李晓阳,李茜.基于中医传承辅助系统的毕荣修教授治疗激素性股骨头坏死处方规律探析[J].中国实验方剂学杂志,2016,22(19):177-181.
[8] Xue XH,Feng ZH,Li ZX,et al. Salidroside inhibits steroid- induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway:In vitro and in vivo studies [J]. Mol Med Rep,2018,17(3):3751-3757.
[9] Zhan J,Yan Z,Zhao M,et al. Allicin inhibits osteoblast apoptosis and steroid-induced necrosis of femoral head progression by activating the PI3K/AKT pathway [J]. Food Funct, 2020,11(9):7830-7841.
[10] 陈晓波,陈雷雷,洪郭驹,等.桃红四物汤对激素性股骨头坏死兔股骨头微结构的影响及其机制[J].山东医药,2017,57(32):5-9.
[11] 梁红锁,杨业静,刘雷,等.普伐他汀灌胃与股骨头局部给药对兔激素性股骨头坏死的干预效果比较[J].山东医药,2021,61(26):43-46.
[12] Ren X,Fan W,Shao Z,et al. A metabolomic study on early detection of steroid-induced avascular necrosis of the femoral head [J]. Oncotarget,2018,9(8):7984-7995.
[13] 喻钧伦,罗天友,吴少平,等.激素联合脂多糖建立股骨头缺血坏死模型兔的技术改良[J].中国组织工程研究,2015,19(20):3129-3133.
[14] 杨雯静,黄健,王维,等.基于网络药理学和体外细胞实验探究“三七-骨碎补”药对活性成分治疗骨质疏松症的作用机制[J].中国中药杂志,2023,48(4):1087-1097.
[15] 张玉苗,刘洋,刘艳平,等.基于网络药理学和细胞实验探讨杜仲+续断药对治疗骨质疏松症的作用机制[J].中国药理学通报,2022,38(9):1401-1408.
[16] 张孙正远,李峻昊,章喻,等.牛膝-杜仲药对治疗糖皮质激素性骨质疏松症的网络药理学分析[J].中药新药与临床药理,2022,33(10):1377-1385.
[17] 李志鸿,叶学劲,刘经鹏,等.当归-骨碎补配伍治疗骨折三期辨证中期的网络药理学机制[J].广州中医药大学学报,2021,38(8):1693-1699.
[18] 周正新,朱磊,李文华,等.中药骨痹通消颗粒通过调控Wnt/β-catenin通路治疗激素性股骨头坏死的实验研究[J].中华中医药学刊,2023,41(1):21-24.
[19] 阎晓霞,韩崇涛,赵志强,等.补肾生骨方治疗股骨头坏死[J].中医学报,2022,37(8):1754-1759.
[20] 付涛,吴晓东,阿力艾拜.水飞蓟宾通过PI3K/AKT/FoxO1通路改善骨质疏松大鼠骨代谢和骨量[J].中国骨质疏松杂志,2020,26(10):1416-1420.
[21] 石威,金鑫,王金凤,等.淫羊藿苷介导PI3K/Akt信号通路干预大鼠早期激素性股骨头坏死的研究[J].现代药物与临床,2022,37(12):2680-2686.
[22] Bartell SM,Kim HN,Ambrogini E,et al. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation [J]. Nat Commun,2014,5:3773.
[23] Zhang X,Tang N,Hadden TJ,et al. Akt,FoxO and regulation of apoptosis [J]. Biochim Biophys Acta,2011,1813(11):1978-1986.
[24] 于海洋,卢增鹏,汪海燕,等.激素性股骨头坏死中Hif-1α/ VEGF信号轴和H型血管改变的实验研究[J].中国实验动物学报,2022,30(6):759-766.
[25] 曹林忠,汪小敏,张虎林,等.生骨再造丸对兔激素性股骨头坏死VEGF及FLT-1表达的影响[J].中国临床药理学与治疗学,2018,23(8):874-880.
[26] 刘孟初,曹林忠,蒋玮,等.PI3K/AKT/mTOR信号通路在糖皮质激素性股骨头坏死中的表达与作用[J].中华骨质疏松和骨矿盐疾病杂志,2021,14(1):87-93. |
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