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目的探讨血管紧张素Ⅱ受体拮抗剂(angiotension receptor blocker,ARB)替米沙坦对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块面积及过氧化物酶体增殖物激活受体-δ(peroxisome proliferators-activated receptor-δ,PPAR-δ)、白细胞介素-1β(interleukin-1β,IL-1β)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达的影响。方法载脂蛋白E基因敲除小鼠60只,适应性喂养7d后随机分为普通饲料组(对照组)、高脂饲料组、高脂饲料+替米沙坦组(替米沙坦组)、高脂饲料+氯沙坦组(氯沙坦组)各15只。喂养8周后,采用无创血压系统检测小鼠鼠尾血压;经颈动脉取血检测血清总胆固醇、三酰甘油;采用HE染色评估胸主动脉根部斑块面积,采用Western blot法检测胸主动脉PPAR-δ、IL-1β和TGF-β1蛋白表达情况。结果高脂饲料组、替米沙坦组、氯沙坦组小鼠总胆固醇((15.6±2.3)、(14.8±3.1)、(15.1±2.9)mmol/L)、三酰甘油((3.8±0.6)、(3.5±0.5)、(3.6±0.7)mmol/L)均明显高于对照组((5.9±0.3)、(1.8±0.1)mmol/L)(P<0.01);替米沙坦组、氯沙坦组小鼠收缩压((108±21)、(110±19)mm Hg)低于对照组((119±16)mm Hg)和高脂饲料组((12±25)mm Hg)(P<0.01);替米沙坦组和氯沙坦组小鼠收缩压比较差异无统计学意义(P>0.05);4组小鼠主动脉血管紧张素Ⅱ水平差异无统计学意义(P>0.05);高脂饲料组胸主动脉根部斑块面积((3.31±0.19)×105μm2)、IL-1β水平(2.15±0.32)明显高于对照组((1.39±0.11)×105μm2,0.92±0.10)、替米沙坦组((2.12±0.16)×105μm2,1.08±0.15)和氯沙坦组((2.73±0.13)×105μm2,1.71±0.11)(P<0.05或P<0.01),TGF-β1水平(0.63±0.12)低于对照组(1.80±0.30)、替米沙坦组(1.78±0.25)和氯沙坦组(0.98±0.13)(P<0.05或P<0.01),替米沙坦组胸主动脉根部斑块面积、IL-1β水平低于氯沙坦组(P<0.05),TGF-β1水平高于氯沙坦组(P<0.05);高脂饲料组胸主动脉PPAR-δ水平(0.60±0.10)低于对照组(1.21±0.10)和替米沙坦组(1.42±0.30)(P<0.01),与氯沙坦组(0.62±0.15)比较差异无统计学意义(P>0.05),替米沙坦组高于氯沙坦组(P<0.01)。结论替米沙坦可能部分通过激活PPAR-δ调控炎症因子IL-1β与抗炎因子TGF-β1的分泌,抑制动脉粥样硬化的发生发展。
Objective To investigate the effect of telmisartan on the area of atherosclerotic plaque and the activity of peroxisome proliferator - activated receptor - gammareceptor in apoB - δ (PPAR-δ), interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1) Methods Sixty apolipoprotein E knockout mice were randomly divided into normal diet group (control group), high fat diet group, high fat diet + telmisartan group (telmisartan group) , High-fat diet + losartan group (losartan group) 15 each. After 8 weeks of feeding, the rat tail blood pressure was measured by using a noninvasive blood pressure system. Total cholesterol and triglyceride were determined by carotid artery blood sampling. The plaque area of the thoracic aorta was evaluated by HE staining. The thoracic aorta PPAR-δ, IL-1β and TGF-β1 protein expression. Results The total cholesterol ((15.6 ± 2.3), (14.8 ± 3.1), (15.1 ± 2.9) mmol / L), triglyceride (3.8 ± (5.9 ± 0.3) and (1.8 ± 0.1) mmol / L, respectively) (P <0.01); Telmisartan was significantly higher than that of the control group (0.6 ± 0.6, 3.5 ± 0.5, 3.6 ± 0.7, In the Losartan group, the systolic blood pressure ((108 ± 21) and (110 ± 19) mm Hg) in the losartan group were significantly lower than those in the control group (119 ± 16 mm Hg) and the high fat diet group (12 ± 25 mm Hg) (P <0.01). There was no significant difference in systolic blood pressure between the telmisartan group and the losartan group (P> 0.05). There was no significant difference in the aortic angiotensin Ⅱ level between the 4 groups (3.31 ± 0.19) × 105μm2 and IL-1β (2.15 ± 0.32) in the high-fat diet group were significantly higher than those in the control group (1.39 ± 0.11) × 105μm2, (2.12 ± 0.16) × 105μm2,1.08 ± 0.15) and losartan group ((2.73 ± 0.13) × 105μm2,1.71 ± 0.11) (P <0.05 or P <0.01) , And the level of TGF-β1 (0.63 ± 0.12) was lower in the control group (1.80 ± 0.30), telmisartan group (1.78 ± 0.25) and losartan group (0.98 ± 0.13) Telmisartan thoracic aortic root plaque area, IL-1β (P <0.05), and the level of TGF-β1 in losartan group was higher than that in losartan group (P <0.05). The level of PPAR-δ in thoracic aorta in high fat diet group (0.60 ± 0.10) was lower than that in control group 1.21 ± 0.10) and telmisartan group (1.42 ± 0.30) (P <0.01), but no significant difference with losartan group (0.62 ± 0.15) (P> 0.05), telmisartan group was higher than Losartan group (P <0.01). Conclusion Telmisartan can inhibit the development of atherosclerosis partly by activating the secretion of inflammatory cytokines IL-1β and anti-inflammatory factor TGF-β1 by activating PPAR-δ.