【摘要】 目的探讨脂联素(adiponectin,ADPN)对急性心力衰竭(AHF)大鼠AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)、信号转导子与转录激活子3(signal transducer and activator of transcription 3,STAT3)通路相关蛋白表达变化和血清炎性因子含量变化的影响。方法将30只雄性SD大鼠随机分为对照组(CON组)、模型组(AHF组)和脂联素处理组(AHFADPN组),AHF-ADPN组大鼠尾静脉注射重组脂联素腺病毒7 d(10×10~9pfu,1天1次),AHF组大鼠注射等剂量的生理盐水。AHF组和AHF-ADPN组大鼠通过异丙肾上腺素(isoprenaline,ISO)腹腔注射构建AHF模型。酶联免疫吸附测定方法检测三组大鼠血清B型尿钠肽(B-type natriuretic peptides,BNP)、心肌肌钙蛋白I (cardiac troponin I, c Tn I)、乳酸脱氢酶(lactate dehydrogenase,LDH)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-10(interleukin-10,IL-10)和生长分化因子-15(growthdifferentiation factor-15,GDF-15)含量;高分辨率小动物超声系统比较三组大鼠心率(heart rate,HR)及左室射血分数(left ventricular ejection fraction,LVEF);免疫印迹方法检测三组大鼠pAMPK、AMPK、p-STAT3和STAT3蛋白表达变化。结果①与AHF组比较,AHF-ADPN组血清BNP含量[(286.30±14.03) pg/m L vs.(79.95±0.85) pg/m L]显著下调(P <0.0001),c Tn I含量[(543.80±17.30) pg/m L vs.(147.40±21.39) pg/m L]显著下调(P <0.001),LDH含量[(6.91±0.07) U/L vs.(6.37±0.08) U/L]显著下调(P <0.01)。②与AHF组比较,AHF-ADPN组HR[(335.40±4.67)次/min vs.(387.80±3.74)次/min]显著升高(P <0.001),LVEF[(42.10±2.76)%vs.(79.20±1.93)%]显著升高(P <0.001)。③与AHF组比较,AHF-ADPN组血清IL-6含量[(280.00±4.63) pg/m L vs.(251.70±5.59) pg/m L]显著降低(P <0.01),TNF-α含量[(87.35±2.09) pg/m L vs.(74.42±2.51) pg/m L]显著降低(P <0.001),GDF-15含量[(123.40±3.03)pg/m L vs.(97.69±2.52) pg/m L]显著降低(P <0.001),血清IL-10含量[(101.90±2.46)pg/m L vs.(189.90±4.18) pg/m L]显著升高(P <0.0001)。④AHF-ADPN组p-AMPK及pSTAT3蛋白表达显著高于AHF组(P <0.01)。结论外源ADPN能够显著改善AHF大鼠的血清炎性因子含量,并导致心肌p-AMPK和p-STAT3表达改变,为AHF的治疗提供证据。更多还原

【Abstract】 Objective To investigate the effect of adiponectin( ADPN) on the expression of AMP-activated protein kinase( AMPK)/signal transducer and activator of transcription 3( STAT3)signal pathway and serum inflammatory factors. Methods 30 male Sprague Dawley rats were randomly divided into control( CON) group,acute heart failure( AHF) group and AHF-ADPN group. AHF-ADPN group was injected with recombinant ADPN adenovirus for 7 days( 10 × 109 pfu,tail vein injection,once a day),but AHF was injected with the same dose of normal saline. AHF group and AHF-ADPN group were injected intraperitoneally with isoprenaline( ISO) to construct AHF models. Serum concentrations of B-type natriuretic peptides( BNP),cardiac troponin I( c Tn I),lactate dehydrogenase( LDH),tumor necrosis factor-α( TNF-α),interleukin-6( IL-6),interleukin-10( IL-10)and growth-differentiation factor-15( GDF-15) protein in three groups were detected by ELISA.Heart rate( HR) and left ventricular ejection fraction( LVEF) were detected by ultrasound system. The protein expression of p-AMPK,AMPK,p-STAT3 and STAT3 were detected by Western blotting.Results①Compared with the AHF group,the serum BNP concentrations[( 286. 30 ± 14. 03) pg/m L vs.( 79. 95 ± 0. 85) pg/m L] were significantly lower in the AHF-ADPN group( P < 0. 0001),c Tn I[( 543. 80 ± 17. 30) pg/m L vs.( 147. 40 ± 21. 39) pg/m L] were significantly lower( P < 0. 001),LDH[( 6. 91 ± 0. 07) U/L vs.( 6. 37 ± 0. 08) U/L] were significantly lower( P < 0. 01).②Compared with the AHF group,HR[( 335. 40 ± 4. 67) bpm vs.( 387. 80 ± 3. 74) bpm] was significantly higher( P <0. 001),LVEF[( 42. 10 ±2. 76) % vs.( 79. 20 ± 1. 93) %]was significantly higher in the AHF-ADPN group( P < 0. 001).③ Compared with the AHF group,the serum concentrations of IL-6[( 280. 00 ± 4. 63) pg/m L vs.( 251. 70 ± 5. 59) pg/m L]was significantly lower( P < 0. 01),TNF-α[( 87. 35 ± 2. 09) pg/m L vs.( 74. 42 ± 2. 51) pg/m L]was significantly lower( P < 0. 001),GDF-15[( 123. 40 ± 3. 03) pg/m L vs.( 97. 69 ± 2. 52) pg/m L] was significantly lower in the AHF-ADPN group( P < 0. 001),while the concentration of IL-10[( 101. 90 ± 2. 46) pg/m L vs.( 189. 90 ± 4. 18)pg/m L] was significantly increased in AHF-ADPN group( P < 0. 0001).④ Western blotting results showed that the p-AMPK and p-STAT3 protein were significantly higher in the AHF-ADPN group than in the AHF group( P < 0. 01). Conclusions ADPN can significantly improve the serum inflammatory level in the rats with AHF,and its effect might be achieved by activating the AMPK/STAT3 pathway.更多还原