Effect of remimazolam on apoptosis of intestinal epithelial cells in burned rats by regulating TLR4/MyD88/NF-κB signaling pathway

doi:10.11958/20240667

Abstract

Abstract:

Objective To investigate the effect of remimazolam (Rem) on apoptosis of intestinal epithelial cells in burned rats by regulating Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods The successfully constructed burned rat model was randomly divided into the model group, the Rem low dose treatment (Rem-L) group, the Rem medium dose treatment (Rem-M) group and the Rem high dose treatment (Rem-H) group, and Rem-H+TLR4 activator (LPS) group. Healthy rats were taken as the control group. After blood samples were collected from tail vein of rats and intestinal tissue samples were taken after euthanasia. Serum levels of inflammatory cytokines interleukin-1β and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). HE staining was applied to observe the morphology of intestinal tissue. TUNEL detection kit was used to detect apoptosis. Immunohistochemistry was used to detect the expression of tight junction proteins ZO-1 and Occludin. Immunoblotting experiments were used to detect the expression levels of apoptotic proteins Bax and TLR4/MyD88/NF-κB signaling pathway proteins. Results Compared with the control group, cell arrangement was disordered with inflammation, and IL-1β and IL-6 levels and apoptosis rate were increased, expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were up-regulated, and expression levels of ZO-1 and Occludin were down-regulated in the model group (P<0.05). Compared with the model group, inflammatory infiltration of intestinal mucosa was gradually reduced in the Rem-L, Rem-M and Rem-H groups, the apoptosis rate, IL-1β and IL-6 levels were decreased, the expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were down-regulated, and the expression of ZO-1 and Occludin was up-regulated in a dose-dependent manner (P<0.05). Compared with the Rem-H group, the tissue inflammation was aggravated, the apoptosis rate, levels of IL-1β and IL-6 were increased, expression levels of Bax, TLR4, MyD88 and p-NF-κB/NF-κB were up-regulated, and expression levels of ZO-1 and Occludin were down-regulatedin in the Rem-H+LPS group (P<0.05). Conclusion Remimazolam may alleviate the damage of intestinal epithelial cells in burned model rats by inhibiting TLR4/MyD88/NF-κB signaling pathway, thus protecting intestinal mucosa.

Key words: burns, Toll-like receptor 4, myeloid differentiation factor 88, NF-kappa B, apoptosis, Remimazolam, intestinal epithelial cells

CLC Number:

R644

Figures/Tables 9

References 21

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组别	IL-1β	IL-6
Control组	5.73±0.64	8.64±1.03
Model组	83.47±9.15^a	69.76±7.28^a
Rem-L组	56.83±6.42^b	43.55±5.36^b
Rem-M组	25.39±2.68^bc	29.42±3.34^bc
Rem-H组	13.97±1.82^bcd	16.53±1.90^bcd
Rem-H+LPS组	34.75±3.91^e	32.06±3.79^e
F	200.098^＊＊	150.559^＊＊

组别	IL-1β	IL-6
Control组	5.73±0.64	8.64±1.03
Model组	83.47±9.15^a	69.76±7.28^a
Rem-L组	56.83±6.42^b	43.55±5.36^b
Rem-M组	25.39±2.68^bc	29.42±3.34^bc
Rem-H组	13.97±1.82^bcd	16.53±1.90^bcd
Rem-H+LPS组	34.75±3.91^e	32.06±3.79^e
F	200.098^＊＊	150.559^＊＊

组别	细胞凋亡率/%	Bax
Control组	2.68±0.31	0.32±0.03
Model组	29.67±4.12^a	1.18±0.16^a
Rem-L组	23.54±3.69^b	0.81±0.08^b
Rem-M组	15.38±2.84^bc	0.65±0.06^bc
Rem-H组	10.96±1.25^bcd	0.42±0.04^bcd
Rem-H+LPS组	19.05±2.14^e	0.74±0.07^e
F	72.424^＊＊	78.419^＊＊

组别	细胞凋亡率/%	Bax
Control组	2.68±0.31	0.32±0.03
Model组	29.67±4.12^a	1.18±0.16^a
Rem-L组	23.54±3.69^b	0.81±0.08^b
Rem-M组	15.38±2.84^bc	0.65±0.06^bc
Rem-H组	10.96±1.25^bcd	0.42±0.04^bcd
Rem-H+LPS组	19.05±2.14^e	0.74±0.07^e
F	72.424^＊＊	78.419^＊＊

组别	ZO-1	Occludin
Control组	1.13±0.15	1.25±0.18
Model组	0.30±0.03^a	0.23±0.02^a
Rem-L组	0.53±0.05^b	0.45±0.04^b
Rem-M组	0.76±0.07^bc	0.66±0.06^bc
Rem-H组	0.94±0.11^bcd	0.89±0.09^bcd
Rem-H+LPS组	0.62±0.06^d	0.56±0.05^d
F	68.181^＊＊	94.657^＊＊