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贵州中医药大学基础医学院,贵阳 550025
Received:29 July 2024,
Revised:2024-11-15,
Accepted:20 January 2025,
Published:30 March 2025
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黄垂巧,陈帅,李倩,等.当归补血汤调控中性粒细胞胞外诱捕网改善卵巢早衰大鼠骨质疏松的机制研究[J].中国药房,2025,36(06):655-660.
HUANG Chuiqiao,CHEN Shuai,LI Qian,et al.Study on the mechanism of Danggui buxue decoction regulating neutrophil extracellular traps to improve osteoporosis in rats with premature ovarian failure[J].ZHONGGUO YAOFANG,2025,36(06):655-660.
黄垂巧,陈帅,李倩,等.当归补血汤调控中性粒细胞胞外诱捕网改善卵巢早衰大鼠骨质疏松的机制研究[J].中国药房,2025,36(06):655-660. DOI: 10.6039/j.issn.1001-0408.2025.06.03.
HUANG Chuiqiao,CHEN Shuai,LI Qian,et al.Study on the mechanism of Danggui buxue decoction regulating neutrophil extracellular traps to improve osteoporosis in rats with premature ovarian failure[J].ZHONGGUO YAOFANG,2025,36(06):655-660. DOI: 10.6039/j.issn.1001-0408.2025.06.03.
目的
2
探讨当归补血汤调控中性粒细胞胞外诱捕网(NETs)改善卵巢早衰(POF)大鼠骨质疏松(OP)的机制。
方法
2
将雌性SD大鼠随机分成正常组、模型组、骨化三醇组及当归补血汤低、中、高剂量组,每组9只。除正常组外,其余各组大鼠于第1、8天以6 mg/kg的剂量腹腔注射顺铂溶液建立POF并发OP模型。从造模第5天开始,各组大鼠灌胃相应药液或生理盐水,每天1次,连续4周。末次给药后,检测各组大鼠血清中雌二醇(E
2
)、NETs、25-羟维生素D
3
[25(OH)D
3
]
、核因子κB受体激活蛋白配体(RANKL)、骨钙蛋白(BGP)水平,观察其骨组织病理学改变,并检测其骨组织中维生素D受体(VDR)、髓过氧化物酶(MPO)、中性粒细胞弹性蛋白酶(NE)、瓜氨酸化组蛋白H3(CitH3)、25羟基维生素D-1
α
-羟化酶(CY
P27B1)、1
α
,25-二羟维生素D
3
-24-羟化酶(CYP24A1)蛋白的表达情况。
结果
2
与正常组相比,模型组大鼠骨组织骨小梁数量减少、变细及断裂且连接不完整,网状结构明显受损,骨髓腔增大;血清中NETs、RANKL水平和骨组织中MPO、NE、CitH3、CYP24A1蛋白的表达均显著升高或上调,血清中E
2
、25(OH)D
3
、BGP水平和骨组织中VDR、CYP27B1蛋白的表达均显著降低或下调(
P
<0.05)。与模型组相比,各药物组大鼠骨组织病理学改变均有所恢复,多数定量指标显著改善(
P
<0.05)。
结论
2
当归补血汤能够恢复POF并发OP大鼠的E
2
水平,改善OP,其机制可能与上调VD水平、抑制NETs形成有关。
OBJECTIVE
2
To investigate the mechanism through which Danggui buxue decoction regulates neutrophil extracellular traps (NETs) to improve osteoporosis (OP) in rats with premature ovarian failure (POF).
METHODS
2
Female SD rats were randomly divided into normal group, model group, calcitriol group, and Danggui buxue decoction low-dose, medium-dose and high-dose groups, with 9 rats in each group. Except for the normal group, all other groups were administered cisplatin via intraperitoneal injection on days 1 and 8 to establish a POF complicated with OP model. Each group received the corresponding drugs or normal saline intragastrically starting from day 5, once a day, for 4 consecutive weeks. After the last medication, serum levels of estradiol (E
2
), NETs, 25-hydroxyvitamin D
3
[25(OH)D
3
]
, receptor activator of nuclear factor-κB ligand (RANKL), and osteocalcin (BGP) were measured. The histopathological changes in bone tissue were observed. The expressions of vitamin D receptor (VDR), myeloperoxidase (MPO), neutrophil elastase (NE) and citrullinated histone H3 (CitH3) in bone tissue were detected; the protein expressions of 25-hydroxyvitamin D-1
α
-hydroxylase (CYP27B1) and 1
α
,25-dihydroxyvitamin D
3
-24-hydroxylase (CYP24A1) were also determined.
RESULTS
2
Compared with the normal group, the bone tissue of rats in the model group
showed a significant reduction in the number of trabeculae, which was thinner broken and poorly connected, with significant destruction of the reticular structure, and an enlarged marrow cavity. Serum levels of NETs and RANKL, the protein expressions of MPO, NE, CitH3 and CYP24A1 in bone tissue were significantly increased or upregulated, while serum levels of E
2
, 25(OH)D
3
and BGP as well as protein expressions of VDR and CYP27B1 were significantly decreased or downregulated (
P
<0.05). Compared with the model group, the histopathological changes in the bone tissue of rats in each administration group showed some degree of recovery, with significant improvements observed in most quantitative indicators (
P
<0.05).
CONCLUSIONS
2
Danggui buxue decoction can restore the E
2
level in POF complicated with OP rats, and improve OP. The mechanism may be related to its ability to upregulate VD level and inhibit the formation of NETs.
YOU R X , LIU J Y , KE L , et al . Cost-effectiveness of sequential denosumab/zoledronic acid compared with zoledronic acid monotherapy for postmenopausal osteoporotic women in China [J ] . Front Pharmacol , 2022 , 13 : 816248 .
HAN S Y , LI H X , LU R , et al . Effect and mechanism of pearl on ovarian function of rats with premature ovarian failure induced by Tripterygium glycosides [J ] . J Tradit Complement Med , 2023 , 13 ( 4 ): 368 - 378 .
CHENG C H , CHEN L R , CHEN K H . Osteoporosis due to hormone imbalance:an overview of the effects of estrogen deficiency and glucocorticoid overuse on bone turnover [J ] . Int J Mol Sci , 2022 , 23 ( 3 ): 1376 .
LI X , XIAO S H , FILIPCZAK N , et al . Role and therapeutic targeting strategies of neutrophil extracellular traps in inflammation [J ] . Int J Nanomedicine , 2023 , 18 : 5265 - 5287 .
KIM T S , SILVA L M , THEOFILOU V I , et al . Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis [J ] . J Exp Med , 2023 , 220 ( 9 ): e20221751 .
IANTOMASI T , ROMAGNOLI C , PALMINI G , et al . Oxidative stress and inflammation in osteoporosis:molecular mechanisms involved and the relationship with microRNAs [J ] . Int J Mol Sci , 2023 , 24 ( 4 ): 3772 .
李月兴 , 陈波洋 , 李倩 , 等 . 飞龙掌血对胶原诱发关节炎大鼠心血管损害的干预作用及机制 [J ] . 中国药房 , 2023 , 34 ( 24 ): 2987 - 2994 .
LI Y X , CHEN B Y , LI Q , et al . Intervention effects and mechanism of Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis [J ] . China Pharm , 2023 , 34 ( 24 ): 2987 - 2994 .
董右青 , 朱星 , 沈俊希 , 等 . 补肺汤对COPD大鼠模型中性粒细胞胞外诱捕网及维生素D的影响 [J ] . 中药药理与临床 , 2024 , 40 ( 4 ): 47 - 53 .
DONG Y Q , ZHU X , SHEN J X , et al . Effects of Bufei decoction on extracellular neutrophil traps and vitamin D in COPD rats [J ] . Pharmacol Clin Chin Mater Med , 2024 , 40 ( 4 ): 47 - 53 .
LIU H Q , YANG H , QIN Z , et al . Exploration of the Dang-gui buxue decoction mechanism regulating the balance of ESR and AR in the TP53-AKT signaling pathway in the prevention and treatment of POF [J ] . Evid Based Complement Alternat Med , 2021 , 2021 : 4862164 .
张孟之 , 柴艺汇 , 管连城 , 等 . 当归补血汤对维甲酸致大鼠骨质疏松模型CYP24A1和骨钙素表达的影响 [J ] . 中药药理与临床 , 2019 , 35 ( 1 ): 10 - 14 .
ZHANG M Z , CHAI Y H , GUAN L C , et al . Effect of Danggui buxue decoction on the expression of CYP24A1 and osteocalcin in rat osteoporosis model induced by retinoic acid [J ] . Pharmacol Clin Chin Mater Med , 2019 , 35 ( 1 ): 10 - 14 .
张孟之 , 管连城 , 秦忠 , 等 . 当归补血汤对维甲酸致骨质疏松模型大鼠卵巢CYP24A1和ERα表达的影响 [J ] . 中药新药与临床药理 , 2020 , 31 ( 5 ): 502 - 507 .
ZHANG M Z , GUAN L C , QIN Z , et al . Effect of Danggui buxue decoction on the expression of CYP24A1 and ERα in ovaries of osteoporosis rats induced by retinoic acid [J ] . Tradit Chin Drug Res Clin Pharmacol , 2020 , 31 ( 5 ): 502 - 507 .
巴鑫 , 陈哲 , 黄谣 , 等 . 归肾丸对卵巢早衰大鼠骨密度及骨微结构的影响及其机制研究 [J ] . 中国骨质疏松杂志 , 2023 , 29 ( 3 ): 390 - 396 .
BA X , CHEN Z , HUANG Y , et al . The mechanism and effect of Guishen pill on bone mineral density and microstructure of bone tissue in rats with premature ovarian fai-lure [J ] . Chin J Osteoporos , 2023 , 29 ( 3 ): 390 - 396 .
范雅祺 , 郑燕鹏 , 周子婷 , 等 . 雷公藤建立卵巢早衰大鼠模型的实验研究 [J ] . 中国实验动物学报 , 2023 , 31 ( 3 ): 355 - 364 .
FAN Y Q , ZHENG Y P , ZHOU Z T , et al . Establishment of a rat model of premature ovarian failure induced by Tripterygium wilfordii [J ] . Acta Lab Animalis Sci Sin , 2023 , 31 ( 3 ): 355 - 364 .
PENG X L , WANG T H , WANG Q , et al . Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss [J ] . Cell Commun Signal , 2024 , 22 ( 1 ): 160 .
YANG S L , ZHANG X C , LIAO X F , et al . Icariin regulates RANKL-induced osteoclast differentiation via the ERα/c-Src/RANK signaling [J ] . Biomed Mater , 2024 , 19 ( 2 ): 025049 .
YANG Y M , TSENG W J , WANG B . Abaloparatide maintains normal rat blood calcium level in part via 1,25-dihydroxyvitamin D/osteocalcin signaling pathway [J ] . Endocrinology , 2023 , 164 ( 9 ): bqad117 .
ZHOU L P , WONG K Y , YEUNG H T , et al . Bone protective effects of Danggui buxue tang alone and in combination with tamoxifen or raloxifene in vivo and in vitro [J ] . Front Pharmacol , 2018 , 9 : 779 .
THIAM H R , WONG S L , WAGNER D D , et al . Cellular mechanisms of NETosis [J ] . Annu Rev Cell Dev Biol , 2020 , 36 : 191 - 218 .
NUMAZAKI K , TADA H , NISHIOKA T , et al . Neutrophil extracellular traps inhibit osteoclastogenesis [J ] . Biochem Biophys Res Commun , 2024 , 705 : 149743 .
SCHNEIDER A H , TAIRA T M , PÚBLIO G A , et al . Neutrophil extracellular traps mediate bone erosion in rheumatoid arthritis by enhancing RANKL-induced osteoclastogenesis [J ] . Br J Pharmacol , 2024 , 181 ( 3 ): 429 - 446 .
ZHAO X L , LIN S , LI H Y , et al . Myeloperoxidase controls bone turnover by suppressing osteoclast differentiation through modulating reactive oxygen species level [J ] . J Bone Miner Res , 2021 , 36 ( 3 ): 591 - 603 .
SUGISAKI R , MIYAMOTO Y , YOSHIMURA K , et al . Possible involvement of elastase in enhanced osteoclast differentiation by neutrophils through degradation of osteoprotegerin [J ] . Bone , 2020 , 132 : 115216 .
DELRUE C , SPEECKAERT M M . Vitamin D and vitamin D-binding protein in health and disease [J ] . Int J Mol Sci , 2023 , 24 ( 5 ): 4642 .
THOMAS R L , JIANG L J , ADAMS J S , et al . Vitamin D metabolites and the gut microbiome in older men [J ] . Nat Commun , 2020 , 11 : 5997 .
WANG D M , YANG Y M . The relationship between serum 25-hydroxyvitamin D levels and osteoporosis in postmenopausal women [J ] . Clinical interventions in aging , 2023 , 18 : 619 - 627 .
MADY L J , ZHONG Y , DHAWAN P , et al . Role of co-activator associated arginine methyltransferase 1(CARM1) in the regulation of the biological function of 1,25-dihydroxyvitamin D 3 [J ] . Cells , 2023 , 12 ( 10 ): 1407 .
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