转录因子GATA4介导电针对神经病理性痛大鼠的镇痛作用Spinal transcription factor GATA4 mediated adenosine A1 receptor activation contributes to electroacupuncture analgesia in neuropathic pain rats
金文君;张明晓;王雷雷;戴勤学;
摘要(Abstract):
目的:观察转录因子GATA4是否介导电针对神经病理性痛大鼠的镇痛作用。方法:实验分两部分。第一部分将SD大鼠按照随机数字表法随机分成对照组、GATA4腺病毒干扰RNA(AV-shGATA4 RNA)组和腺病毒空载体(AV-shCTRL)组,每组6只。观察大鼠脊髓GATA4蛋白表达量,评估腺病毒AV-shGATA4 RNA的转染效率。第二部分将30只SD大鼠按照随机数字表法分成假手术组、模型组、电针组、电针复合AV-shGATA4 RNA组、电针复合AV-shCTRL组,每组6只。采用慢性坐骨神经压迫法(CCI)制备大鼠神经病理性疼痛模型。在造模后第7天电针"足三里""太冲"。在电针前48 h,将腺病毒AV-shGATA4和AV-shCTR注射到大鼠脊髓腰(L)4—L6节段。在造模前、造模后第7天和电针后60 min时检测大鼠患肢的机械痛阈值和热痛阈值;采用Western blot法检测脊髓组织中腺苷A1受体和GATA4蛋白表达量。结果:第一部分实验:对照组和AV-shCTRL组比较,大鼠脊髓GATA4蛋白表达量差异无统计学意义(P>0.05)。与AV-shCTRL组相比,AV-shGATA4 RNA组大鼠脊髓GATA4蛋白表达量明显减少(P<0.05)。各组大鼠右后肢机械痛阈值与热敏痛阈值比较差异均无统计学意义(P>0.05)。第二部分实验:在造模后第7天,除假手术组外,各组大鼠的机械痛阈值与热敏痛阈值较造模前明显下降(P<0.05)。在电针后60 min时,与模型组比较,电针组大鼠机械痛和热敏痛阈值明显增加(P<0.05);与电针组和电针复合AV-shCTRL组比较,电针复合AV-shGATA4 RNA组大鼠机械痛和热敏痛阈值明显减小(P<0.05)。与假手术组比较,模型组大鼠脊髓腺苷A1受体和GATA4蛋白表达量明显增加(P<0.05)。与模型组比较,电针组和电针复合AV-shCTRL大鼠脊髓腺苷A1受体和GATA4蛋白表达量明显增加(P<0.05)。与电针组和电针复合AV-shCTRL组比较,电针复合AV-shGATA4 RNA组大鼠脊髓腺苷A1受体和GATA4蛋白表达量明显减少(P<0.05)。结论:电针可以增加CCI大鼠脊髓腺苷A1受体和GATA4蛋白表达量;AV-shGATA4 RNA可以逆转电针增加CCI大鼠脊髓腺苷A1受体蛋白表达以及电针镇痛效应。因此推测转录因子GATA4介导电针对CCI的镇痛作用,其可能的机制是GATA4调控腺苷A1受体的表达进而参与电针镇痛作用。
关键词(KeyWords): 神经病理性痛;电针镇痛;腺苷A1受体;GATA4转录因子
基金项目(Foundation): 国家自然科学基金项目(No.81704180)
作者(Author): 金文君;张明晓;王雷雷;戴勤学;
Email:
DOI: 10.13702/j.1000-0607.200481
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