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目的探讨A型行为得分、外周血单核细胞先天固有免疫系统Toll样受体4(TLR4)和下游炎症因子变化与罹患动脉粥样硬化的关系。方法依据颈动脉超声检查结果将研究对象分为颈动脉粥样硬化组(n=275)和健康对照组(对照组,n=301)。采用明尼苏达多相人格调查表(MMPI)2 A型行为量表评定行为类型(≥11分为A型)。流式细胞术测定外周血CD14~+单核细胞表面TLR4表达,酶联免疫吸附试验(ELISA)法检测血清肾上腺素和去甲肾上腺素、白细胞介素6(IL-6)、白细胞介素18(IL-18)水平。结果颈动脉粥样硬化组A型行为检出率高于对照组(58.68%比24.64%,P<0.01)。颈动脉粥样硬化组血清肾上腺素、去甲肾上腺素水平高于对照组[(17.53±9.98)比(6.83±5.16)μg/L,(863.62±240.58)比(441.17±194.05)ng/L;均P<0.01]。颈动脉粥样硬化组患者单核细胞TLR4表达及IL-6和IL-18水平高于对照组[(14.07±3.54)%比(9.81±3.42)%,(301.87±18.43)比(274.44±13.79)ng/L,(450.39±28.66)比(364.28±34.78)ng/L;均P<0.05]。无论是颈动脉粥样硬化组还是对照组,A型行为者单核细胞TLR4、血清IL-6和IL-18、肾上腺素和去甲肾上腺素水平均高于非A型行为者。多因素Logistic回归分析发现:男性、年龄、高血压、心血管病家族史、A型行为、敌意得分、TLR4表达、血清IL-6和IL-18水平是罹患颈动脉粥样硬化的独立影响因素。结论颈动脉粥样硬化患者交感神经活化程度高于健康人;A型行为者交感神经活化程度、单核细胞TLR4蛋白表达及血清炎症水平高于非A型行为者;A型行为、单核细胞TLR4蛋白表达及血清炎症水平与罹患颈动脉粥样硬化存在相关性。
Objective To investigate the relationship between type A behavior score, changes of innate innate immune system Toll-like receptor 4 (TLR4) and downstream inflammatory cytokines in peripheral blood mononuclear cells and atherosclerosis. Methods According to the results of carotid ultrasonography, the subjects were divided into carotid atherosclerosis group (n = 275) and healthy control group (n = 301). The Minnesota Multiphasic Personality Inventory (MMPI) 2 Type A Behavior Scale was used to assess the type of behavior (≥11 divided into Type A). Flow cytometry was used to detect the expression of TLR4 on the surface of CD14 ~ + monocytes in peripheral blood. Serum epinephrine and norepinephrine, interleukin 6 (IL-6), interleukin 18 (IL-18) levels. Results The detection rate of type A behavior in carotid atherosclerosis group was higher than that in control group (58.68% vs 24.64%, P <0.01). The levels of serum epinephrine and norepinephrine in carotid atherosclerosis group were significantly higher than those in control group [(17.53 ± 9.98) vs (6.83 ± 5.16) μg / L, (863.62 ± 240.58) vs (441.17 ± 194.05) ng / L, All P <0.01]. The expression of TLR4 and the levels of IL-6 and IL-18 in monocytes of patients with carotid atherosclerosis were significantly higher than that of the control group [(14.07 ± 3.54)% vs (9.81 ± 3.42)% vs (301.87 ± 18.43) vs (274.44 ± 13.79 ) ng / L, (450.39 ± 28.66) vs (364.28 ± 34.78) ng / L, all P <0.05]. The TLR4, IL-6, IL-18, adrenergic and norepinephrine levels of monocytes in type A carriers were higher than those in non-type A carriers in both carotid atherosclerosis and control groups. Multivariate logistic regression analysis found that male, age, hypertension, family history of cardiovascular disease, type A behavior, hostility score, TLR4 expression, serum IL-6 and IL-18 levels were independent risk factors for carotid atherosclerosis . Conclusion The activation of sympathetic nerve in patients with carotid atherosclerosis is higher than that in healthy people. The activation of sympathetic nerve, the expression of TLR4 protein in monocytes and the level of serum inflammation in type A patients are higher than those in non-type A patients. Type A behaviors, mononuclear cells The expression of TLR4 protein and the level of serum inflammation correlated with the presence of carotid atherosclerosis.