Effects of linezolid on bacterial load and bone repair in rats with chronic osteomyelitis induced by MRSA infection

doi:10.11958/20221569

Abstract

Abstract:

Objective To explore the effects of linezolid on bacterial load and bone repair in rats with chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. Methods A total of 45 Wistar rats were randomly and averagely divided into the sham operation group, the model group and the linezolid group, 15 rats in each group. Rats in the model group and the linezolid group were inoculated with 10 μL of MRSA (1×10⁸ CFU/mL) after bilateral proximal tibia bone defects to construct rat models of chronic osteomyelitis. At 7 d after modeling, rats in the linezolid group was intraperitoneally injected with linezolid (54 mg/kg), while the sham operation group and the model group were given the same volume of glucose injection for 14 d. The wound healing, scores of Rissing and tibia X-ray Norden, and bacterial load were observed. The pathological changes of tibia tissue were observed by HE staining. The levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-1β and IL-6 in skeletal muscle tissue around lesions were detected by enzyme-linked immunosorbent assay. The expression levels of TGF-β1, activin receptor-like kinase 1 (ALK-1), Smad1/5, p-Smad1/5 and bone morphogenetic protein 2 (BMP-2) in tibial tissue were detected by Western blot assay. Results All the sham operation group healed in class-A. In the model group, there were 3 rats with class-B healing and 12 rats with class-C healing. In the linezolid group, there were 9 rats with class-B healing and 6 rats with class-C healing, there was a significant difference between the two groups (χ²=35.111, P<0.01). Rissing score, Norden score and bacterial load were lower in the linezolid group than those in the model group (P<0.05). In the model group, there were local bone destruction, intramedullary and subperiosteal abscesses, inflammatory cell infiltration and local fibrosis. In the linezolid group, bone destruction, inflammatory cell infiltration and fibrosis were significantly relieved. Compared with the sham operation group, levels of TGF-β1, IL-1β and IL-6 in skeletal muscle tissue, and expression levels of TGF-β1, ALK-1 and p-Smad1/5 in tibia tissue were increased, while BMP-2 was decreased in the model group (P<0.05). Compared with the model group, linezolid intervention could reverse changes of the above indexes (P<0.05). Conclusion Linezolid can relieve bacterial load and promote bone repair in rats with chronic osteomyelitis induced by MRSA infection by inhibiting the activation of TGF-β/BMP pathways.

Key words: osteomyelitis, methicillin-resistant staphylococcus aureus, linezolid, transforming growth factor beta1, bone morphogenetic protein 2, activin receptors, type Ⅰ, Smad proteins

CLC Number:

R681.21

Figures/Tables 5

References 22

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组别	Rissing评分/分	Norden评分/分	细菌负荷/（CFU/mL）
模型组	2.85±0.32	2.75±0.43	2.13±0.42
利奈唑胺组	1.62±0.38	1.35±0.31	0.51±0.04
t	9.589^＊＊	10.229^＊＊	14.871^＊＊

组别	Rissing评分/分	Norden评分/分	细菌负荷/（CFU/mL）
模型组	2.85±0.32	2.75±0.43	2.13±0.42
利奈唑胺组	1.62±0.38	1.35±0.31	0.51±0.04
t	9.589^＊＊	10.229^＊＊	14.871^＊＊

组别	TGF-β1	IL-1β	IL-6
假手术组	21.24±5.17	29.51±6.12	11.35±2.42
模型组	185.18±16.51^a	115.32±25.73^a	69.51±17.64^a
利奈唑胺组	75.35±23.48^ab	58.25±14.38^ab	28.61±7.25^ab
F	369.144^＊＊	94.726^＊＊	108.634^＊＊

组别	TGF-β1	IL-1β	IL-6
假手术组	21.24±5.17	29.51±6.12	11.35±2.42
模型组	185.18±16.51^a	115.32±25.73^a	69.51±17.64^a
利奈唑胺组	75.35±23.48^ab	58.25±14.38^ab	28.61±7.25^ab
F	369.144^＊＊	94.726^＊＊	108.634^＊＊

组别	TGF-β1	ALK-1	p-Smad1/5	BMP-2
假手术组	0.42±0.07	0.31±0.05	0.35±0.06	0.53±0.09
模型组	1.18±0.25^a	1.32±0.27^a	0.95±0.24^a	0.35±0.06^a
利奈唑胺组	0.78±0.14^ab	0.65±0.18^ab	0.67±0.17^ab	0.42±0.07^ab
F	74.759^＊＊	110.246^＊＊	45.017^＊＊	22.319^＊＊