Improvement effect of myricitrin on bone defect in rats with bacterial osteomyelitis

doi:10.11958/20230188

Abstract

Abstract:

Objective To explore the improvement effect of myricitrin on bone defect in rats with bacterial osteomyelitis (OM) through vascular endothelial growth factor A (VEGFA)/stromal cell-derived factor (SDF-1)/C-X-C chemokine receptor 4(CXCR4) pathway. Methods Rats were randomly divided into the sham operation group, the OM group, the myricitrin group [50 mg/(kg?d)], PX-478 group [25 mg/(kg?d) VEGFA/SDF-1/CXCR4 signaling pathway inhibitor PX-478], and the myricitrin+PX-478 group [50 mg/(kg?d) myricitrin and 25 mg/(kg?d) PX-478], 18 mice per group. Bilateral proximal tibia bone defects were used to construct bacterial OM rat model. After 12 weeks of continuous treatment, the wound healing degree of rats was observed, and anal temperature of rats was measured. The serum inflammatory factors interleukin (IL)-6, IL-1β, IL-17 and bone metabolism indexes bone alkaline phosphatase (BALP), osteocalcin (BGP) and C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ) were measured by enzyma-linked immunosorbent assay (ELISA). The bacterial load of tissue around the lesion was detected. HE staining was used to detect the pathological changes of the tissue around lesions. The expression of CD31 was detected by immunofluorescence staining. Western blot assay was used to detect the expression of VEGFA/SDF-1/CXCR4 signal pathway related proteins. Results Compared with the sham operation group, the number of rats with grade A wound healing, BALP and BGP levels, CD31 positive area, VEGFA, SDF-1 and CXCR4 protein levels were decreased in the OM group (P<0.005 or P<0.05), and the anal temperature, bacterial load, IL-6, IL-1β, IL-17 and CTX-Ⅰ levels were increased (P<0.05). Compared with the OM group, the BALP and BGP levels, CD31 positive area, VEGFA, SDF-1 and CXCR4 protein levels were increased, and the anal temperature, bacterial load, IL-6, IL-1β, IL-17 and CTX-Ⅰ levels were decreased in the myricitrin group (P<0.05). Results of PX-478 group showed the opposite trend. PX-478 reversed the effect of myricitrin on the improvement of bone defects in bacterial OM rats. Conclusion Myricitrin may improve bone defect of OM rats by activating the VEGFA/SDF-1/CXCR4 signal pathway.

Key words: osteomyelitis, vascular endothelial growth factor A, chemokine CXCL12, receptors, CXCR4, myricitrin, bone defect, angiogenesis

CLC Number:

R681.21

Figures/Tables 7

References 21

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组别	甲级创口愈合（n=18）/只	肛温（n=18）/℃	细菌负荷（n=6）/（×10⁵ CFU/mL）
假手术组	18	35.39±0.38	0.00±0.00
OM组	9^a	37.35±0.44^a	2.04±0.28^a
杨梅苷组	14	35.69±0.36^b	0.65±0.04^b
PX-478组	5	38.73±0.65^b	3.32±0.36^b
杨梅苷+PX-478组	10	37.46±0.54^c	2.33±0.25^c
χ²或F	23.351^＊＊	144.827^＊＊	196.369^＊＊

组别	甲级创口愈合（n=18）/只	肛温（n=18）/℃	细菌负荷（n=6）/（×10⁵ CFU/mL）
假手术组	18	35.39±0.38	0.00±0.00
OM组	9^a	37.35±0.44^a	2.04±0.28^a
杨梅苷组	14	35.69±0.36^b	0.65±0.04^b
PX-478组	5	38.73±0.65^b	3.32±0.36^b
杨梅苷+PX-478组	10	37.46±0.54^c	2.33±0.25^c
χ²或F	23.351^＊＊	144.827^＊＊	196.369^＊＊

组别	IL-6	IL-1β	IL-17
假手术组	47.32±6.34	34.23±8.87	1.89±0.25
OM组	73.84±9.56^a	69.43±16.98^a	4.38±0.52^a
杨梅苷组	53.43±6.13^b	44.97±6.56^b	2.15±0.36^b
PX-478组	97.87±11.32^b	93.86±14.87^b	5.98±0.65^b
杨梅苷+PX-478组	69.65±8.43^c	57.56±6.57^c	3.91±0.45^c
F	95.779^＊＊	71.118^＊＊	235.371^＊＊

组别	IL-6	IL-1β	IL-17
假手术组	47.32±6.34	34.23±8.87	1.89±0.25
OM组	73.84±9.56^a	69.43±16.98^a	4.38±0.52^a
杨梅苷组	53.43±6.13^b	44.97±6.56^b	2.15±0.36^b
PX-478组	97.87±11.32^b	93.86±14.87^b	5.98±0.65^b
杨梅苷+PX-478组	69.65±8.43^c	57.56±6.57^c	3.91±0.45^c
F	95.779^＊＊	71.118^＊＊	235.371^＊＊

组别	BALP	BGP	CTX-Ⅰ
假手术组	8.47±0.94	15.86±1.69	0.55±0.04
OM组	5.68±0.68^a	9.57±0.94^a	1.39±0.15^a
杨梅苷组	7.94±0.84^b	14.86±1.57^b	0.65±0.07^b
PX-478组	3.31±0.25^b	6.43±0.72^b	1.97±0.23^b
杨梅苷+PX-478组	5.98±0.78^c	10.53±1.76^c	1.22±0.13^c
F	139.029^＊＊	138.927^＊＊	306.237^＊＊