骨碎补总黄酮改善激素性股骨头坏死脂代谢紊乱的作用机制

doi:10.11958/20252085

天津医药 ›› 2025, Vol. 53 ›› Issue (11): 1138-1144.doi: 10.11958/20252085

骨碎补总黄酮改善激素性股骨头坏死脂代谢紊乱的作用机制

苏艺(), 周金良, 丁强^△()

河南省洛阳正骨医院（河南省骨科医院）髋关节外二科（邮编 450016 ）

收稿日期:2025-05-27 修回日期:2025-08-07 出版日期:2025-11-15 发布日期:2025-11-19
通讯作者: △E-mail: dingqiang5227@126.com
作者简介:苏艺（1989），男，主治医师，主要从事髋关节及下肢疾患的保守及手术治疗方面研究。E-mail：suyilk@163.com
基金资助:
河南省中医药科学研究专项课题(2023ZY2118)

The mechanism of total flavonoids of Rhizoma drynariae improving lipid metabolism disorders in steroid-induced avascular necrosis of femoral head in rabbits

SU Yi(), ZHOU Jinliang, DING Qiang^△()

Department II of Hip Joint Surgery, Henan Provincial Orthopaedic Hospital, Luoyang Orthopaedic Hospital, Zhengzhou 450016, China

Received:2025-05-27 Revised:2025-08-07 Published:2025-11-15 Online:2025-11-19
Contact: △E-mail: dingqiang5227@126.com

苏艺, 周金良, 丁强. 骨碎补总黄酮改善激素性股骨头坏死脂代谢紊乱的作用机制[J]. 天津医药, 2025, 53(11): 1138-1144.

SU Yi, ZHOU Jinliang, DING Qiang. The mechanism of total flavonoids of Rhizoma drynariae improving lipid metabolism disorders in steroid-induced avascular necrosis of femoral head in rabbits[J]. Tianjin Medical Journal, 2025, 53(11): 1138-1144.

摘要/Abstract

摘要：

目的探讨基于过氧化物酶体增殖物激活受体γ（PPARγ）/腺苷酸活化蛋白激酶（AMPK）通路探讨骨碎补总黄酮（TFRD）改善激素性股骨头坏死（SANFH）兔脂代谢紊乱的作用机制。方法将60只新西兰兔随机分为对照组（10只）和造模组（50只）。采用注射大肠杆菌内毒素联合甲泼尼龙的方法建立兔SANFH模型；对照组注射等量生理盐水。造模组再随机分为SANFH组、TFRD-低组（30 mg/kg）、TFRD-中组（60 mg/kg）、TFRD-高组（100 mg/kg）、TFRD-高+抑制剂组（100 mg/kg TFRD+30 mg/kg化合物C，AMPK抑制剂）5组，每组10只。干预结束后，采集兔耳缘静脉血，检测血清血脂指标[高密度脂蛋白胆固醇（HDL-C）、总胆固醇、甘油三酯（TG）]；Micro-CT检测骨体积/总体积（BV/TV）、骨小梁数量（Tb.N）；HE染色观察股骨组织病理学变化并计算空骨陷窝率；TUNEL法检测骨细胞凋亡率；实时荧光定量PCR检测骨组织B细胞淋巴瘤/白血病-2（Bcl-2）和Bcl-2相关X蛋白（Bax）mRNA表达；Western blot检测骨组织PPARγ、p-AMPK/AMPK表达。结果与对照组相比，SANFH组HDL-C、BV/TV、Tb.N、Bcl-2 mRNA、PPARγ、p-AMPK/AMPK表达水平降低，胆固醇、TG、凋亡率、空骨陷窝率、Bax mRNA表达水平升高（P<0.05）；与SANFH组相比，TFRD-低、中、高组的HDL-C、BV/TV、Tb.N、Bcl-2 mRNA、PPARγ、p-AMPK/AMPK表达水平依次升高，胆固醇、TG、凋亡率、空骨陷窝率、Bax mRNA表达水平依次降低（P<0.05）；与TFRD-高组相比，TFRD-高+抑制剂组上述指标变化被逆转（P<0.05）。结论 TFRD可能通过激活PPARγ/AMPK通路改善SANFH兔脂代谢紊乱。

关键词: 股骨头坏死, 激素类, 脂代谢障碍, 骨碎补, 黄酮类, PPARγ, AMP活化蛋白激酶类

Abstract:

Objective To explore the mechanism of action of total flavonoids of Rhizoma drynariae (TFRD) in improving lipid metabolism disorders in rabbits with avascular necrosis of femoral head (SANFH) based on the peroxisome proliferator-activated receptor γ (PPARγ)/adenosine monophosphate-activated protein kinase (AMPK) pathway. Methods Sixty New Zealand rabbits were randomly divided into the control group (n=10) and the model group (n=50). The rabbit SANFH model was established by injecting Escherichia coli endotoxin and methylprednisolone. The control group was injected with the same amount of physiological saline. The SANFH model was randomly classified into five subgroups: the SANFH group, the TFRD-low group (30 mg/kg), the TFRD-medium group (60 mg/kg), the TFRD-high group (100 mg/kg) and the TFRD-high+inhibitor (TFRD 100 mg/kg + AMPK inhibiter 30 mg/kg) group, with 10 rabbits in each subgroup. After the intervention, venous blood sample was collected from the rabbit ear margin, and serum lipid levels [high-density lipoprotein cholesterol (HDL-C) and total cholesterol, triglycerides (TG)] were detected. Micro-CT was used to detect bone volume/total volume (BV/TV) (%) and trabecular quantity (Tb.N). Hematoxylin-eosin (HE) staining was used to observe histopathological changes of femur and calculate empty bone lacuna rate. TUNEL was used to detect apoptosis of femoral tissue. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to analyze the expression of B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2-related X protein (Bax) mRNA. Western blot assay was used to detect the expression of tissue-related proteins (PPARγ and p-AMPK/AMPK). Results Compared with the control group, HDL-C, BV/TV, Tb.N, Bcl-2 mRNAs, PPARγ and p-AMPK/AMPK were decreased in the SANFH group, and cholesterol, TG, apoptosis rate, empty bone lacuna rate and Bax mRNA were increased (P<0.05). Compared with the SANFH group, HDL-C, BV/TV, Tb.N, Bcl-2 mRNAs, PPARγ and p-AMPK/AMPK were increased in sequence in the TFRD-low group, the TFRD-medium group and the TFRD-high group, and cholesterol, TG, apoptosis rate, empty bone lacuna rate and Bax mRNA were decreased in turn (P<0.05). Compared with the TFRD-high group, changes in the above indicators were reversed in the TFRD-high+inhibitor group (P<0.05). Conclusion TFRD improves lipid metabolism disorder in SANFH rabbits by activating PPARγ/AMPK pathway.

Key words: femur head necrosis, hormones, lipid metabolism disorders, drynariae rhizoma, flavanoids, PPAR gamma, AMP-activated protein kinases

中图分类号:

R285.5

图/表 10

参考文献 26

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基因名称	引物序列（5'→3'）	产物大小/bp
Bax	上游：CCCGAGAGGTCTTTTTCCGAG	152
Bax	下游：CCAGCCCATGATGGTTCTGAT	152
Bcl-2	上游：GGTGGGGTCATGTGTGTGG	197
Bcl-2	下游：CGGTTCAGGTACTCAGTCATCC	197
β-actin	上游：TCAGGTCATCACTATCGGCAAT	134
β-actin	下游：AAAGAAAGGGTGTAAAACGCA	134

基因名称	引物序列（5'→3'）	产物大小/bp
Bax	上游：CCCGAGAGGTCTTTTTCCGAG	152
Bax	下游：CCAGCCCATGATGGTTCTGAT	152
Bcl-2	上游：GGTGGGGTCATGTGTGTGG	197
Bcl-2	下游：CGGTTCAGGTACTCAGTCATCC	197
β-actin	上游：TCAGGTCATCACTATCGGCAAT	134
β-actin	下游：AAAGAAAGGGTGTAAAACGCA	134

组别	HDL-C	总胆固醇	TG
对照组	1.75±0.18	0.33±0.04	1.05±0.11
SANFH组	0.58±0.06^a	1.11±0.12^a	2.65±0.26^a
TFRD-低组	0.85±0.09^b	0.78±0.08^b	2.05±0.20^b
TFRD-中组	1.22±0.13^bc	0.52±0.06^bc	1.42±0.14^bc
TFRD-高组	1.71±0.18^bcd	0.35±0.04^bcd	1.08±0.11^bcd
TFRD-高+抑制剂组	0.88±0.09^e	0.81±0.09^e	1.95±0.20^e
F	137.728^＊	155.765^＊	123.687^＊

组别	HDL-C	总胆固醇	TG
对照组	1.75±0.18	0.33±0.04	1.05±0.11
SANFH组	0.58±0.06^a	1.11±0.12^a	2.65±0.26^a
TFRD-低组	0.85±0.09^b	0.78±0.08^b	2.05±0.20^b
TFRD-中组	1.22±0.13^bc	0.52±0.06^bc	1.42±0.14^bc
TFRD-高组	1.71±0.18^bcd	0.35±0.04^bcd	1.08±0.11^bcd
TFRD-高+抑制剂组	0.88±0.09^e	0.81±0.09^e	1.95±0.20^e
F	137.728^＊	155.765^＊	123.687^＊

组别	BV/TV/%	Tb.N/mm^-1
对照组	45.05±4.53	2.64±0.28
SANFH组	17.22±1.79^a	0.98±0.10^a
TFRD-低组	25.31±2.61^b	1.35±0.14^b
TFRD-中组	33.62±3.42^bc	1.86±0.19^bc
TFRD-高组	44.23±4.51^bcd	2.54±0.26^bcd
TFRD-高+抑制剂组	25.44±2.61^e	1.41±0.15^e
F	108.701^＊	117.015^＊

骨碎补总黄酮改善激素性股骨头坏死脂代谢紊乱的作用机制

The mechanism of total flavonoids of Rhizoma drynariae improving lipid metabolism disorders in steroid-induced avascular necrosis of femoral head in rabbits

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参考文献 26

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组别	空骨陷窝率/%	凋亡率/%
对照组	13.26±1.40	4.22±0.48
SANFH组	30.34±3.11^a	30.64±3.12^a
TFRD-低组	22.84±2.31^b	20.64±2.10^b
TFRD-中组	16.85±1.71^bc	14.25±1.51^bc
TFRD-高组	13.55±1.42^bcd	8.52±0.91^bcd
TFRD-高+抑制剂组	21.94±2.22^e	19.85±2.05^e
F	96.336^＊	247.749^＊

组别	Bcl-2	Bax
对照组	0.92±0.10	1.03±0.11
SANFH组	0.22±0.03^a	2.77±0.29^a
TFRD-低组	0.44±0.05^b	2.11±0.23^b
TFRD-中组	0.65±0.07^bc	1.55±0.16^bc
TFRD-高组	0.89±0.09^bcd	1.08±0.12^bcd
TFRD-高+抑制剂组	0.51±0.06^e	2.09±0.21^e
F	146.780^＊	117.843^＊

组别	p-AMPK/AMPK	PPARγ/β-actin
对照组	0.88±0.09	1.51±0.16
SANFH组	0.16±0.02^a	0.55±0.06^a
TFRD-低组	0.35±0.04^b	0.78±0.09^b
TFRD-中组	0.58±0.06^bc	1.02±0.11^bc
TFRD-高组	0.82±0.09^bcd	1.48±0.15^bcd
TFRD-高+抑制剂组	0.41±0.05^e	0.76±0.08^e
F	193.942^＊	122.258^＊

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