七氟烷调控Wnt/β-catenin信号通路对脓毒症急性肺损伤的保护机制

doi:10.3969/j.issn.1006-5725.2025.19.006

Abstract

Abstract:

Objective To explore the role of sevoflurane （SEV） in sepsis-induced acute lung injury （ALI） and observe its impact on the Wnt/β-catenin signaling pathway. Methods Forty C57 mice were randomly divided into 4 groups （n = 10 each）： Sham， CLP， SEV， and SEV + XAV （β-catenin inhibitor）. A sepsis model was established via cecal ligation and puncture. Lung injury was evaluated using HE staining， lung wet/dry weight ratio， and TUNEL staining. Levels of inflammatory factors （TNF-α， IL-1β， IL-6） were detected by ELISA. Oxidative stress indices （SOD， MDA， ROS） were measured by colorimetry and flow cytometry. Hindlimb blood perfusion and oxygenation were assessed with laser speckle flowmetry. Expressions of key Wnt pathway molecules and downstream target genes （c-Myc， Cyclin D1） were detected by RT-qPCR and Western blot. Co-localization of β-catenin and SP-C （a marker of type Ⅱ alveolar epithelial cells） in lung tissues was determined by immunofluorescence staining. Results Compared with the Sham group， the CLP group exhibited significant increases in sepsis severity， lung pathological damage including alveolar structure destruction， inflammatory infiltration， and apoptosis， elevation in pro-inflammatory cytokine levels， and significant decrease in SOD and increase in MDA and ROS. Additionally， lower limb blood flow and oxygenation levels were significantly reduced， while the expression of β-catenin and its downstream target genes， as well as the co-localization signal and fluorescence intensity of β-catenin with SP-C， were significantly downregulated （all P < 0.05）. Compared with the CLP group， the SEV group showed significant improvements in all these indicators. However， compared with the SEV group， the SEV + XAV group demonstrated a reversed protective effect， with all indicators approaching the levels observed in the CLP group （all P < 0.05）. Conclusion Sevoflurane alleviates sepsis-induced ALI by activating Wnt/β-catenin signaling pathway， exerting anti-inflammatory and antioxidant effects， and enhancing the expression and localization of β-catenin in type Ⅱ alveolar epithelial cells.

Key words: sevoflurane, Wnt/β-catenin, sepsis-induced acute lung injury, oxidative stress, type Ⅱ alveolar epithelial cells

CLC Number:

R563.1

Jinyan GUO,Yuqing YOU,Ke CHEN,Fen PAN,Jiahui LAI,Sufang CHEN,Weifeng. YAO. Protective mechanism of sevoflurane on acute lung injury in sepsis by regulating the Wnt/β-catenin signaling pathway[J]. The Journal of Practical Medicine, 2025, 41(19): 2991-2999.

Figures/Tables 11

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References 32

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基因名称	基因长度/bp	上游序列	下游序列	基因符号
β?catenin	150	ATGGAACCAGACAGAAAAGC	CTAGTCATTGCAATTTTGC	Ctnnb1
c?Myc	120	GGCTCCTGGCAAAAGGTCA	CTGCGTAGTTGTGCTGATGT	Myc
Cyclin D1	180	GCTGCGAAGTGGAAACCATC	CCTCCTTCTGCACACATTTGAA	Ccnd1
GSK?3β	150	TTGGAGCCACTGATTACACG	CCAACTGATCCACACCACTG	Gsk3b
GAPDH	100	GAAGGTGAAGGTCGGAGTCA	CATGGGTGGAATCATATTGGAA	GAPDH

组别	例数	肺组织评分/分	每视野细胞凋亡	肺湿/干比
Sham组	10	1.90 ± 0.74	32.80 ± 6.36	2.79 ± 0.47
CLP组	10	9.50 ± 1.84^??	264.29 ± 39.04^?	6.62 ± 0.85
SEV组	10	7.30 ± 0.95^ΔΔ	214.61 ± 36.21^ΔΔΔ	5.18 ± 0.92^Δ
SEV + XAV组	10	10.10 ± 2.42^###	265.72 ± 35.61^#	6.87 ± 0.84^##
F值		52.13	117.42	56.13
P值		< 0.001	< 0.001	< 0.001

组别	例数	SOD/（U/mgprot）	MDA/（mmol/mgprot）	ROS/（AU/mgprot）
Sham组	10	213.59 ± 20.72	0.64 ± 0.16	94.85 ± 26.80
CLP组	10	80.63 ± 25.08^?	2.92 ± 0.50^?	423.23 ± 77.83^?
SEV组	10	109.12 ± 28.05^Δ	2.22 ± 0.54^Δ	290.67 ± 82.34^ΔΔ
SEV + XAV组	10	72.19 ± 17.16^##	3.19 ± 0.52^#	453.03 ± 75.53^##
F值		79.2	62.5	55.3
P值		< 0.001	< 0.001	< 0.001

组别	例数	IL?1β/（pg/mL）	TNF?α/（pg/mL）	IL?6/（pg/mL）
Sham组	10	22.38 ± 10.08	27.84 ± 13.6	129.21 ± 72.60
CLP组	10	144.45 ± 25.24^?	146.80 ± 23.78^?	953.68 ± 199.98^?
SEV组	10	112.88 ± 20.24^Δ	111.27 ± 18.00^Δ	700.13 ± 149.31^ΔΔ
SEV + XAV组	10	147.55 ± 26.04^##	142.70 ± 23.76^##	973.18 ± 201.09^###
F值		74.84	74.38	57.31
P值		< 0.001	< 0.001	< 0.001

组别	例数	β-catenin mRNA	c-Myc mRNA	Cyclin D1 mRNA	GSK-3β mRNA
Sham组	10	1.83 ± 0.44	1.75 ± 0.52	1.23 ± 0.40	0.79 ± 0.18
CLP组	10	1.14 ± 0.28^??	0.84 ± 0.40^??	0.61 ± 0.32^??	1.25 ± 0.38^?
SEV组	10	1.59 ± 0.42^Δ	1.44 ± 0.58^Δ	0.83 ± 0.53^Δ	0.74 ± 0.20^ΔΔ
SEV + XAV组	10	0.98 ± 0.30^#	0.68 ± 0.22^#	0.54 ± 0.29^#	0.99 ± 0.32^#
F值		11.92	7.25	3.39	7.00
P值		< 0.001	< 0.001	<0.05	<0.001

Protective mechanism of sevoflurane on acute lung injury in sepsis by regulating the Wnt/β-catenin signaling pathway

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组别	例数	β-catenin	c-Myc	Cyclin D1	p-GSK-3β
Sham组	10	2.09 ± 0.44	1.61 ± 0.25	2.00 ± 0.39	1.08 ± 0.32
CLP组	10	1.73 ± 0.48^??	0.96 ± 0.35^??	1.38 ± 0.27^?	0.59 ± 0.21^??
SEV组	10	2.08 ± 0.45^Δ	1.49 ± 0.32^ΔΔ	1.60 ± 0.53^Δ	1.20 ± 0.36^Δ
SEV + XAV组	10	1.50 ± 0.32^##	0.77 ± 0.36^#	1.02 ± 0.30^#	0.71 ± 0.29^#
F值		11.49	7.25	3.39	7.00
P值		< 0.001	< 0.001	< 0.05	< 0.001

组别	例数	β-catenin 荧光强度	SP-C 荧光强度
Sham组	10	567.93 ± 69.33	437.87 ± 72.47
CLP组	10	247.64 ± 70.28^**	156.42 ± 89.44^*
SEV组	10	379.98 ± 82.62^Δ	281.44 ± 63.52^ΔΔ
SEV + XAV组	10	211.48 ± 59.36^##	135.28 ± 77.51^#
F值		51.78	33.29
P值		< 0.001	< 0.001

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