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目的 :探讨血管紧张素1型受体(AT_1R)拮抗剂厄贝沙坦对老年高血压患者心脑血栓事件发生的影响及相关机制。方法:入选170例年龄大于60岁的高血压患者,根据用药情况分为厄贝沙坦组(n=100)和氨氯地平组(n=70),比较随访过程中发生血栓事件如脑梗死、心肌梗死发生率的差异;分别测定各组血小板聚集率(PAR)、血管紧张素Ⅱ(AngⅡ)、环氧化酶-2(COX-2)、凝血噁恶烷B2(TXB2)水平。检测经体外培养人主动脉内皮细胞(HAEC)中,由AngⅡ诱导产生的COX-2 m RNA及蛋白表达量、TXB2水平。结果 :厄贝沙坦组患者中PAR(%)明显低于氨氯地平组患者(11.52±0.70比18.71±2.47,P<0.001),其血浆COX-2水平[(76.01±7.09)U/L比(116.40±15.89)U/L,P<0.001]和TXB2[(1 687.00±59.14)ng/L比(2 207.00±180.20)ng/L,P<0.001]也明显降低,且血浆COX-2和TXB2水平降低同PAR降低存在相关性(r=0.109,P<0.001)。中位随访时间18个月,血栓事件的发生率在服用厄贝沙坦的患者中明显降低(15.0%比32.8%,P=0.002)。厄贝沙坦预处理后HAEC后可明显抑制AngⅡ(100 nmol/L)诱导细胞产生的COX-2、TXB2水平。结论 :AT_1R拮抗剂厄贝沙坦抑制COX-2/TXB2表达,能有效抑制老年高血压患者的血小板活性,从而抑制老年高血压患者心脑血栓事件发生风险。
Objective: To investigate the effect of irbesartan, an angiotensin 1 receptor (AT1R) antagonist, on the occurrence of cardiovascular and cerebrovascular events in elderly patients with hypertension and its related mechanisms. Methods: One hundred and seventy patients with hypertension over 60 years of age were enrolled and divided into irbesartan group (n = 100) and amlodipine group (n = 70) according to their medication status. Thrombotic events such as cerebral infarction , Myocardial infarction rate; the platelet aggregation rate (PAR), angiotensin Ⅱ (AngⅡ), cyclooxygenase-2 (COX-2) and thromboxane B2 (TXB2) The expression of COX-2 mRNA and protein, the level of TXB2 induced by AngⅡin cultured human aortic endothelial cells (HAECs) were detected. Results: The PAR (%) in irbesartan group was significantly lower than that in amlodipine group (11.52 ± 0.70 vs 18.71 ± 2.47, P <0.001), and the plasma COX-2 level was (76.01 ± 7.09) U / L (116.40 ± 15.89) U / L, P <0.001] and TXB2 [(1 687.00 ± 59.14) ng / L, compared with 2 207.00 ± 180.20 ng / L, P <0.001] There was a correlation between decreased TXB2 level and decreased PAR (r = 0.109, P <0.001). At a median follow-up of 18 months, the incidence of thrombotic events was significantly lower in patients taking irbesartan (15.0% vs 32.8%, P = 0.002). After pretreatment with irbesartan, HAEC significantly inhibited the COX-2 and TXB2 levels induced by AngⅡ (100 nmol / L). CONCLUSION: Irbesartan, an AT1R antagonist, inhibits COX-2 / TXB2 expression and effectively inhibits platelet activity in elderly hypertensive patients and thus inhibits the risk of cardiovascular and cerebrovascular events in elderly hypertensive patients.