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·药学研究·
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
Δ
*
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黄垂巧 ,陈 帅,李 倩,管连城,高 洁,秦 忠,陈云志(贵州中医药大学基础医学院,贵阳 550025)
中图分类号 R965;R285 文献标志码 A 文章编号 1001-0408(2025)06-0655-06
DOI 10.6039/j.issn.1001-0408.2025.06.03
摘 要 目的 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 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(E2 )、NETs、25-羟维生素 D3[25(OH)D3]、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-1α-羟化酶(CYP27B1)、1α,25-二羟维生素D3-24-羟化酶
(CYP24A1)蛋白的表达情况。结果 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
E2、25(OH)D3、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 当归补血汤能够恢复 POF 并发 OP 大鼠的 E2水平,改善
OP,其机制可能与上调VD水平、抑制NETs形成有关。
关键词 当归补血汤;卵巢早衰;骨质疏松;中性粒细胞胞外诱捕网;维生素D
Study on the mechanism of Danggui buxue decoction regulating neutrophil extracellular traps to improve
osteoporosis in rats with premature ovarian failure
HUANG Chuiqiao,CHEN Shuai,LI Qian,GUAN Liancheng,GAO Jie,QIN Zhong,CHEN Yunzhi(School of
Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China)
ABSTRACT OBJECTIVE 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 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 (E2 ), NETs, 25-hydroxyvitamin D3 [25(OH)D3], 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-1α-hydroxylase (CYP27B1) and 1α,25-dihydroxyvitamin D3-24-hydroxylase (CYP24A1)
were also determined. RESULTS 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 E2, 25(OH)D3 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 Danggui buxue decoction can restore the
E2 level in POF complicated with OP rats, and improve OP.
Δ 基金项目 国家自然科学基金项目(No.82260890);贵州省教育
The mechanism may be related to its ability to upregulate VD
厅滚动支持省属高校科研平台团队项目(No.黔教技〔2022〕023号) level and inhibit the formation of NETs.
*第一作者 硕士研究生。研究方向:中医证候物质基础。E-
mail:1065183702@qq.com KEYWORDS Danggui buxue decoction; premature ovarian
failure; osteoporosis; neutrophil extracellular traps; vitamin D
# 通信作者 教授,博士生导师,博士。研究方向:中医证候物质基
础。E-mail:chenyunzhi270@gzy.edu.cn
中国药房 2025年第36卷第6期 China Pharmacy 2025 Vol. 36 No. 6 · 655 ·