Study of Etomidate Protecting against Nucleus Pulposus Degeneration in Rats with Intervertebral Disc Degeneration by Mediating the Mitochondrial Apoptotic Pathway
YI Jin
XIAO Xiaozhu
LI Yuewei
WANG Jianmin
YANG Guanghui
WENG Weizong
Abstract：Objective To study the effects of etomidate on apoptosis of nucleus pulposus cells,matrix metabolism and mitochondrial function in rats with intervertebral disc degeneration(IVD).Methods Fifty healthy male SPF-grade rats were selected,and a SD rat models of IVD were established by needle puncture and divided into the model group,etomidate(1.5,3.0,6.0 mg/kg)groups,and the control group,with 10 rats in each group.After surgery,the etomidate groups received daily intraperitoneal injections of the corresponding doses of etomidate for one week;the control group and model group received an equal volume of saline.Histopathology and cell apoptosis were evaluated by hematoxylin-eosin staining and TUNEL staining,respectively.Western blot,real-time quantitative PCR,and enzyme-linked immunosorbent assay were used to analyze protein and mRNA expression of key factors[such as cleaved caspase-3/9,matrix metalloproteinase(MMP),Aggrecan,type Ⅱ collagen(COL-Ⅱ),etc.]and mitochondrial function indicators[superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),Bax/Bcl-2 ratio,c-Myc].Results In the model group,the boundary between the nucleus pulposus and annulus fibrosus in degenerated discs was disrupted,and there was a high distribution of TUNEL-positive cells in the nucleus pulposus.In the etomidate(3.0 and 6.0 mg/kg)groups,the interface damage was alleviated,and TUNEL-positive cells were reduced.Compared with the control group,the model group showed increased protein expressions of cleaved caspase-3,cleaved caspase-9,MMP-1,and MMP-3,elevated mRNA expressions of MMP-1 and MMP-3(P<0.05),decreased protein expressions of Aggrecan,COL-Ⅱ,sex determining region Y box protein-6(SOX-6),SOX-9,and tissue inhibitor of matrix metalloproteinase-1(TIMP-1),reduced TIMP-1 mRNA expression(P<0.05),increased mitochondrial MDA and GSH-Px levels and Bax/Bcl-2 ratio(P<0.05),as well as decreased mitochondrial SOD activity and c-Myc protein expression(P<0.05).Compared with the model group and the etomidate(1.5 mg/kg)group,the etomidate(3.0 and 6.0 mg/kg)groups exhibited decreased protein expressions of cleaved caspase-3,cleaved caspase-9,MMP-1,and MMP-3,reduced mRNA expressions of MMP-1 and MMP-3(P<0.05),increased protein expressions of Aggrecan,COL-Ⅱ,SOX-6,SOX-9,and TIMP-1,elevated TIMP-1 mRNA expression(P<0.05),lowered mitochondrial MDA and GSH-Px levels and Bax/Bcl-2 ratio(P<0.05),and enhanced mitochondrial SOD activity and c-Myc protein expression(P<0.05).Conclusion Etomidate can inhibit apoptosis of nucleus pulposus cells,improve matrix metabolism,and alleviate mitochondrial function damage in rats with intervertebral disc degeneration.
Keywords：intervertebral disc degenerationratsdisease modelsanimaletomidatemitochondriaapoptosismatrix metabolism
Publication Date：2025-10-20
Online Publishing Date：2025-10-28(First online date of this platform, not the publication date of the document)
Pages：7( 125-131 )