摘要
【目的】探讨抗氧化剂普罗布考、AT1受体拮抗剂厄贝沙坦对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肝脏磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/Akt信号转导途径中Akt的影响。【方法】40只SHR随机分为SHR对照组、SHR普罗布考组[61 mg·(kg·d)-1]、SHR厄贝沙坦组[50 mg·(kg·d)-1]、SHR联合用药组共4组,另设WKY对照组。采用灌胃给药12周后,测定大鼠体质量、心率、血压和空腹血糖。用Western Blotting方法测定肝脏Akt及其2种磷酸化形式(p-Akt Thr 308,p-Akt Ser473)蛋白表达量的变化。【结果】4组SHR大鼠体质量(300.3±33.2、314.2±37.2、315.3±31.4、322.3±32.5)g、心率(446.3±28.29、433.6±35.63、429.7±25.68、436.1±30.87)次/min、空腹血糖水平[(5.80±0.56、5.79±0.57、5.49±0.60、5.60±0.87)mmol/l]未见明显差异(P>0.05),厄贝沙坦组和联合用药组血压低于对照组[(179.3±6.95、169.2±5.35)mm Hg vs(218.0±10.59)mm Hg(1 mm Hg=0.1333 k Pa),P<0.01]。4组SHR及WKY大鼠肝脏Akt相对蛋白含量未见明显差异。普罗布考组、厄贝沙坦组及联合用药组大鼠肝脏p-Ak(tThr308)相对蛋白含量均高于SHR对照组[(0.305±0.06、0.388±0.05、0.583±0.08)vs(0.102±0.03),P<0.05],其中联合用药组升高最为明显;厄贝沙坦组、联合用药组肝脏p-Ak(tSer473)相对蛋白含量则均低于SHR对照组[(0.389±0.03、0.312±0.02)vs(0.498±0.03),P<0.05]。【结论】肝脏胰岛素PI3K/Akt信号转导通路中Akt蛋白Thr308位点的磷酸化受损可能是导致SHR胰岛素抵抗的原因之一;普罗布考和厄贝沙坦改善SHR胰岛素抵抗的作用或许与其增加肝脏Akt Thr308位点的磷酸化水平有关。
【Objective】To investigate the effects of probucol and irbesartan on insulin PI3K/ Akt signaling pathway in liver of SHR.【Methods】A total of 40 SHR was randomly divided into 4 groups： control group（C）, probucol group（Pro）, irbesartan group（Irb） and combined therapy group（Pro＋Irb）, and treated respectively with placebo, probucol[61 mg·（kg·d）-1], irbesartan[50 mg·（kg·d）-1]and both tested drugs, and in addition WKY control group was set. After intragastric adminstration was adoped for 12 weeks, Fasting glucose,weight, heart rate and blood pressure were measured. The change of the key protein of the insulin PI3K/ Akt signaling pathway of SHR after treated with probucol and irbesartan was measured by the method of western blotting.【Results】No difference of the level of body mass,heart rates,fasting blood-glucose[（300.3±33.2、314.2±37.2、315.3±31.4、322.3±32.5）g,P〉0.05][（446.3±28.29、433.6±35.63、429.7±25.68、436.1±30.87）bpm,P〉0.05][（5.80±0.56、5.79±0.57、5.49±0.60、5.60±0.87）mmol/l,P〉0.05]. The blood pressure of SHRIrb and SHR- Pro ＋ Irb group were lower than those of SHR- C group[（179.3±6.95、169.2±5.35）vs（218.0±10.59）,P〈0.01]. There had no difference of the level of liver Akt relative protein in SHR groups and WKY group. Compared to SHR-C group,the level of liver pAkt（Thr308）relative protein of the other three SHR groups were higher[（0.102±0.03）vs（0.305±0.06、0.388±0.05、0.583±0.08）,P〈0.05],among the three groups,SHR-Pro＋Irb group was the most highest. The level of liver p-Akt（Ser473）relative protein of the SHR-Irb and SHR-Pro＋Irb group were lower than that of SHR-C group[（0.389±0.03、0.312±0.02）vs（0.498±0.03）,P〈0.05].【Conclusion】The impairment of the phosphorylation of Akt Thr308 in insulin PI3K/Akt signaling pathway of liver may be the contributory cause for SHR insulin resistance. Combination of probucol and irbesartan could improve the insulin sensitivity by increasing t
出处
《武警后勤学院学报（医学版）》
CAS
2015年第4期257-261,共5页
Journal of Logistics University of PAP（Medical Sciences）
基金
武警医学院科研重点项目(WKH2008Z05)
