瑞芬太尼调节HIF-1α/BNIP3通路对骨关节炎大鼠软骨损伤的影响

doi:10.11958/20253579

天津医药 ›› 2026, Vol. 54 ›› Issue (7): 699-704.doi: 10.11958/20253579

瑞芬太尼调节HIF-1α/BNIP3通路对骨关节炎大鼠软骨损伤的影响

吕大鹏¹(), 周红荣¹, 李丹¹, 周娜²

¹ 衡水市中医医院麻醉科（邮编053000）
² 河北省中医院（河北中医药大学第一附属医院）麻醉科

收稿日期:2025-12-11 修回日期:2026-03-17 出版日期:2026-07-15 发布日期:2026-07-13
作者简介:吕大鹏（1975），男，副主任医师，主要从事麻醉方面研究。E-mail：15297663790@163.com
基金资助:
河北省中医药管理局科研计划项目(2022622)

The effect of remifentanil on cartilage damage in osteoarthritis rats by regulating the HIF-1α/BNIP3 pathway

LYU Dapeng¹(), ZHOU Hongrong¹, LI Dan¹, ZHOU Na²

¹ Department of Anesthesiology, Hengshui Traditional Chinese Medicine Hospital, Hengshui 053000, China
² Department of Anesthesiology, Hebei Provincial Hospital of Traditional Chinese Medicine (First Affiliated Hospital of Hebei University of Traditional Chinese Medicine)

Received:2025-12-11 Revised:2026-03-17 Published:2026-07-15 Online:2026-07-13

吕大鹏, 周红荣, 李丹, 周娜. 瑞芬太尼调节HIF-1α/BNIP3通路对骨关节炎大鼠软骨损伤的影响[J]. 天津医药, 2026, 54(7): 699-704.

LYU Dapeng, ZHOU Hongrong, LI Dan, ZHOU Na. The effect of remifentanil on cartilage damage in osteoarthritis rats by regulating the HIF-1α/BNIP3 pathway[J]. Tianjin Medical Journal, 2026, 54(7): 699-704.

摘要/Abstract

摘要：

目的探讨瑞芬太尼（Rem）调节缺氧诱导因子-1α（HIF-1α）/腺病毒E1B19kD相互作用蛋白3（BNIP3）通路对骨关节炎（OA）大鼠软骨损伤的影响。方法将50只SPF级SD雄性大鼠随机分为Sham组、OA组、Rem低剂量（Rem-L）组、Rem高剂量（Rem-H）组、Rem-H+YC-1（HIF-1α抑制剂）组，建立OA模型。酶联免疫吸附试验（ELISA）检测大鼠血清单核细胞趋化蛋白-1（MCP-1）、白细胞介素（IL）-18、IL-10、Ⅰ型胶原羧基端肽（CTX-Ⅰ）、Ⅱ型胶原羧基端肽（CTX-Ⅱ）水平；苏木精-伊红（HE）染色、透射电镜观察软骨组织病理变化、结构变化；TUNEL染色检测软骨细胞凋亡；试剂盒检测软骨组织一氧化氮（NO）和丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性；Western blot检测基质金属蛋白酶（MMP）-3、MMP-13、微管相关蛋白1轻链3-Ⅱ（LC3Ⅱ）/微管相关蛋白1轻链3-Ⅰ（LC3Ⅰ）、p62和HIF-1α/BNIP3通路蛋白表达。结果与OA组比较，Rem-L组和Rem-H组大鼠软骨组织形态有明显改善，软骨细胞细胞核和线粒体结构损伤程度降低，血清IL-18、MCP-1、CTX-Ⅰ、CTX-Ⅱ水平，Mankin评分，软骨细胞凋亡率，软骨组织NO和MDA含量，MMP-3、MMP-13和p62蛋白表达水平降低；血清IL-10水平，软骨组织SOD活性，LC3Ⅱ/LC3Ⅰ、HIF-1α和BNIP3蛋白表达水平升高（P<0.05）；YC-1可降低Rem对OA大鼠软骨损伤的改善作用（P<0.05）。结论 Rem可改善OA大鼠软骨损伤，可能与激活HIF-1α/BNIP3通路有关。

关键词: 瑞芬太尼, 骨关节炎, 缺氧诱导因子1，α亚基, 腺病毒E1B蛋白质类, 软骨

Abstract:

Objective To investigate the effect of remifentanil (Rem) on cartilage damage in osteoarthritis (OA) rats by regulating the hypoxia-inducible factor-1α (HIF-1α)/adenovirus E1B19kD interaction protein 3 (BNIP3) pathway. Methods A total of 50 SPF-grade SD male rats were randomly divided into the sham group, the OA group, the Rem low-dose (Rem-L) group, the Rem high-dose (Rem-H) group and the Rem-H +YC-1 (HIF-1α inhibitor) group. OA model was established. Serum levels of monocyte chemotactic protein-1 (MCP-1), interleukin (IL) -18, IL-10, type I collagen carboxy-terminal peptide (CTX-Ⅰ) and type Ⅱ collagen carboxy-terminal peptide (CTX-Ⅱ) were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining and transmission electron microscopy were used to observe pathological changes and structural alterations in cartilage tissue. Chondrocyte apoptosis was detected by TUNEL staining. The content of nitric oxide (NO), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by test kit. Matrix metalloproteinase 3 (MMP-3), matrix metalloproteinase 13 (MMP-13), microtubule-associated protein 1 light chain 3-Ⅱ (LC3Ⅱ)/microtubule-associated protein 1 light chain 3-Ⅰ (LC3Ⅰ), p62 and HIF-1α/BNIP3 pathway protein expression were detected by Western blot analysis. Results Compared with the OA group, cartilage tissue morphology of rats was significantly improved in the Rem-L group and the Rem-H group, and the extent of chondrocyte nuclear and mitochondrial structural damage was reduced, the serum IL-18, MCP-1, CTX-Ⅰ, CTX-Ⅱ, Mankin score, apoptosis rate of chondrocytes, content of NO and MDA in cartilage tissue, MMP-3, MMP-13 and p62 protein expression levels were reduced, while the serum IL-10 level, SOD activity in cartilage tissue, LC3 Ⅱ/LC3 Ⅰ, HIF-1α and BNIP3 protein expression levels were increased (P<0.05). YC-1 could reduce the improvement effect of Rem on cartilage damage in OA rats (P<0.05). Conclusion Rem can improve cartilage injury in OA rats, which may be related to the activation of HIF-1α/BNIP3 pathway.

Key words: remifentanil, osteoarthritis, hypoxia-inducible factor 1, alpha subunit, adenovirus E1B proteins, cartilage

中图分类号:

R684.3

图/表 8

参考文献 22

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组别	IL-18			IL-10
Sham组	9.43±1.28			38.54±4.73
OA组	47.68±5.93^a			6.29±0.84^a
Rem-L组	34.52±4.61^b			17.36±2.58^b
Rem-H组	23.76±3.14^bc			29.62±3.71^bc
Rem-H+YC-1组	38.29±4.72^d			14.81±1.96^d
F	119.339^＊＊			72.948^＊＊
组别		MCP-1	CTX-Ⅰ		CTX-Ⅱ
Sham组		11.74±1.59	11.24±1.68		8.06±1.17
OA组		56.48±7.16^a	29.67±3.82^a		19.58±2.34^a
Rem-L组		39.51±5.74^b	22.43±3.27^b		15.62±1.93^b
Rem-H组		21.65±3.28^bc	15.36±1.94^bc		11.37±1.48^bc
Rem-H+YC-1组		42.92±5.87^d	24.75±3.53^d		16.83±1.56^d
F		119.570^＊＊	61.429^＊＊		68.734^＊＊

组别	IL-18			IL-10
Sham组	9.43±1.28			38.54±4.73
OA组	47.68±5.93^a			6.29±0.84^a
Rem-L组	34.52±4.61^b			17.36±2.58^b
Rem-H组	23.76±3.14^bc			29.62±3.71^bc
Rem-H+YC-1组	38.29±4.72^d			14.81±1.96^d
F	119.339^＊＊			72.948^＊＊
组别		MCP-1	CTX-Ⅰ		CTX-Ⅱ
Sham组		11.74±1.59	11.24±1.68		8.06±1.17
OA组		56.48±7.16^a	29.67±3.82^a		19.58±2.34^a
Rem-L组		39.51±5.74^b	22.43±3.27^b		15.62±1.93^b
Rem-H组		21.65±3.28^bc	15.36±1.94^bc		11.37±1.48^bc
Rem-H+YC-1组		42.92±5.87^d	24.75±3.53^d		16.83±1.56^d
F		119.570^＊＊	61.429^＊＊		68.734^＊＊

组别	Mankin评分/分	凋亡率/%
Sham组	0.40±0.07	1.34±0.17
OA组	9.60±1.38^a	19.86±2.41^a
Rem-L组	7.30±1.16^b	14.75±1.83^b
Rem-H组	4.50±0.74^bc	7.63±0.94^bc
Rem-H+YC-1组	7.90±1.23^d	15.92±1.78^d
F	121.938^＊＊	205.273^＊＊

组别	Mankin评分/分	凋亡率/%
Sham组	0.40±0.07	1.34±0.17
OA组	9.60±1.38^a	19.86±2.41^a
Rem-L组	7.30±1.16^b	14.75±1.83^b
Rem-H组	4.50±0.74^bc	7.63±0.94^bc
Rem-H+YC-1组	7.90±1.23^d	15.92±1.78^d
F	121.938^＊＊	205.273^＊＊

组别	NO/（ng/L）	MDA/（mol/g）	SOD/（U/mg）
Sham组	18.47±2.16	2.09±0.28	83.52±10.64
OA组	93.12±12.84^a	8.34±1.16^a	17.68±2.23^a
Rem-L组	65.83±7.92^b	6.25±0.79^b	39.47±5.48^b
Rem-H组	42.76±5.41^bc	3.81±0.45^bc	62.93±8.17^bc
Rem-H+YC-1组	71.54±9.38^d	6.67±0.84^d	34.26±4.72^d
F	117.033^＊＊	103.419^＊＊	140.391^＊＊

瑞芬太尼调节HIF-1α/BNIP3通路对骨关节炎大鼠软骨损伤的影响

The effect of remifentanil on cartilage damage in osteoarthritis rats by regulating the HIF-1α/BNIP3 pathway

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参考文献 22

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组别	MMP-3/β-actin			MMP-13/β-actin		LC3Ⅱ/LC3Ⅰ
Sham组	0.31±0.05			0.39±0.06		0.95±0.12
OA组	1.07±0.13^a			1.25±0.16^a		0.28±0.04^a
Rem-L组	0.82±0.10^b			0.93±0.12^b		0.46±0.07^b
Rem-H组	0.57±0.08^bc			0.65±0.08^bc		0.78±0.10^bc
Rem-H+YC-1组	0.89±0.11^d			0.98±0.12^d		0.41±0.06^d
F	91.670^＊＊			84.317^＊＊		112.362^＊＊
组别		p62/β-actin	HIF-1α/β-actin		BNIP3/β-actin
Sham组		0.16±0.03	0.85±0.11		1.41±0.17
OA组		0.72±0.09^a	0.24±0.04^a		0.43±0.06^a
Rem-L组		0.54±0.07^b	0.48±0.07^b		0.76±0.09^b
Rem-H组		0.35±0.05^bc	0.67±0.09^bc		1.12±0.14^bc
Rem-H+YC-1组		0.59±0.08^d	0.43±0.06^d		0.63±0.08^d
F		105.417^＊＊	90.149^＊＊		115.878^＊＊

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