摘要
目的 Toll 样受体4(TLR4)的激活与动脉粥样斑块的进展及斑块的不稳定导致临床并发症的发生有关。他汀类调脂药物临床获益可能与其调脂以外的作用尤其是抗炎作用有关,但抗炎作用的确切机制目前还不清楚。推测其抗炎作用可能是通过抑制 TLR4炎症信号通路起作用的。方法入选者为健康志愿者(n=22)及2006-07-2007-09在门诊和住院患者共121例[稳定性心绞痛(SAP)患者17例,急性冠脉综合征(ACS)患者82例],入院即刻抽取外周静脉血;将其中的41例 ACS 患者随机分为两组:在常规抗心绞痛治疗的基础上服用阿托伐他汀10 mg 组(20例)及阿托伐他汀40 mg 组(21例),治疗1月后抽取外周静脉血。观察指标为血脂、高敏 C 反应蛋白(hsCRP)、外周血 CD_(14)^+单核细胞表面 TLR4的表达,单核细胞表面 TLR4的表达采用流式细胞仪方法测定。结果 ACS 患者血 hsCRP 及外周血 CD_(14)^+单核细胞表面 TLR4的表达明显高于 SAP 患者(P<0.05)及正常对照组(P<0.05),hsCRP 与 TLR4的相关性分析结果是两者轻度相关(r=0.261,P=0.002)。ACS 患者经不同剂量阿托伐他汀治疗一月后血总胆固醇和 LDL-C 明显降低(P<0.05),40 mg 的作用较10 mg 作用明显(P<0.05);治疗后血 hsCRP 及外周血 CD4+单核细胞表面 TLR4的表达较治疗前明显下降,其中40 mg 的作用明显强于10 mg。结论 ACS 的发生与冠心病患者单核细胞表面 TLR4表达明显上调有关。阿托伐他汀能显著降低 ACS 患者血hsCRP 和外周血 CD_(14)^+单核细胞表面 TLR4的表达,推测阿托伐他汀抗炎作用可能部分通过抑制 TLR4炎症信号通路起作用的。
Objective Previous studies indicated that activation of Toll-like receptor4 （TLR4） was involved in the progression and instability of atherosclerotic plaque. Anti-inflammatory effects were shown in statins. However, the mechanisms underlying these effects have not been well explored. We test the hypothesis that a portion of these anti-inflammatory effects are mediated by regulation of TLR4 expression. Methods One hundred twenty-one subjects （ 22 normal persons, 17 patients with stable angina and 82 patients with ACS） were recruited. 41 patients with ACS were randomized to atorvastatin 10 mg/d or atorvastatin 40 mg/d on top of routine anti-anginal treatment. Serum level of hsCRP, blood lipids, TLR4 expression on CD14^＋ monocytes were measuered before and after one month treatment. TLR4 expression on CD14^＋ monocytes were quantified via flow-cytometry. Results hsCRP and TLR4 expression on CD14^＋ monocytes in patients with ACS were higher than patients with stable angina and normal persons（hsCRP, ACS：11.1±14.3 vs stable angina：2.5±2.7 mg/L vs normal：2.3±4. 2 mg/L, P〈 0. 05; TLR4, ACS： 32. 3±18. 4 vs stable angina：22.4%±12.2% vs normal subjects：15.6%±7.5%, P〈0.05）. Serum hsCRP and TLR4 expression on CD4＋ monocytes in patients with ACS were decreased after one month treatment with atorvastatin （P〈0. 05）. Greater effect of atorvastatin 40 mg/d on TLR4 expression than that of atorvastatin 10 mg/d（P〈0. 05） was shown. Conclusion ACS is associated with enhanced expression of TLR4 in circulating monocytes. The anti-inflammatory effect by atorvastatin may be partially mediated by down-regulating the expression of TLR4.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2008年第5期422-426,共5页
Chinese Journal of Hypertension
