Effects of lipopolysaccharide-induced toll-like receptor 4 on endoplasmic reticulum stress in atherosclerotic plaques of polipoprotein E gene knockout mice / 中华老年医学杂志

ABSTRACT

Objective:To investigate the effects of endoplasmic reticulum(ER)stress on the stability of atherosclerotic plaques in mice by examining the action of lipopolysaccharide(LPS)-induced Toll-like receptor 4(TLR4)on the protein expression levels in the ER stress pathway in atherosclerotic plaques of polipoprotein E gene knockout (ApoE -/-) mice. Methods:From October 2015 to February 2016, 24 ApoE -/-mice were randomly divided into the control group, the LPS group and the TAK group after 10 weeks of high-fat feeding(n=8, each group). After 10 weeks of intervention, peripheral blood was extracted by removing the eyeballs for the measurement of total cholesterol(TC), triglycerides(TG)and oxidized low density lipoprotein(ox-LDL). Then mice were sacrificed to obtain carotid and aortic specimens.Immunohistochemistry was used to detect the expression of carotid plaque macrophages(MOMA-2), smooth muscle actin(α-actin), TLR4, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNFα)and nuclear factor-κ-gene binding(NFκB). Western blotting was used to determine the expression of PKR-like eukaryotic initiation factor 2αkinase(PERK), C/EBP-homologous protein(CHOP)and glucose-regulated protein 78(GRP78). Results:The levels of TC, TG and ox-LDL were elevated in the LPS group, compared with the control and TAK groups[(25.0±2.3) mmol/L vs. (20.2±1.6) mmol/L and (20.8±2.6) mmol/L, (1.3±0.1) mmol/L vs.(1.3±0.1) mmol/L and (1.0±0.1) mmol/L, (17.4±1.3) mmol/L vs.(15.8±1.6) mmol/L and (12.1±1.1) mmol/L, P<0.05]. The comparison of plaque morphology and pathology showed that the LPS group had a wider range of atherosclerotic plaques, more macrophages and fewer vascular smooth muscle cells than the control and TAK groups( P<0.05). The expression of TLR4, IL-1β, IL-6, TNFα, NFκB, PERK, CHOP and GRP78 was higher in the LPS group than in the control and TAK groups( P<0.05). Compared with the control group, the expression of PERK, CHOP and GRP78 was lower in the TAK group( P<0.05). The expression of TLR4, PERK, CHOP and GRP78 was higher in the LPS group. Conclusions:LPS-induced TLR4 can up-regulate the expression of proteins in the ER stress pathway, increase the secretion of inflammatory cytokines downstream of the ER stress pathway, aggravate lipid metabolism disorders and increase the instability of atherosclerotic plaques.