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

doi:10.11958/20253579

Abstract

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

CLC Number:

R684.3

Figures/Tables 8

References 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^＊＊