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目的观察脑干网状结构内注射腺苷A1受体激动剂苯基异丙基腺苷(R-PIA)对大鼠的镇痛作用及其机制。方法雄性SD大鼠,建立脑干网状结构内置管模型,置管后1周模型制备成功的60只大鼠随机分为12组(n=5):对照组、R-PIA0．5组、R-PIA1．0组、R-PIA2．0组、茶碱(腺苷受体阻滞剂)组、DPCPX(腺苷A1受体阻滞剂8-环戊二丙基黄嘌呤)组、格列本脲(ATP-敏感型钾通道阻滞剂)组、4-AP(电压依赖型钾通道阻滞剂4-氨基吡啶)组、R-PIA2．0+茶碱组、R-PIA2．0+DPCPX组、R- PIA2．0+格列本脲组、R-PIA2．0+4．AP组。前8组注射生理盐水后15 min分别注射生理盐水、R-PIA 0．5μg、R-PIA 1．0μg、R-PIA 2．0μg、茶碱5．0μg、DPCPX 1．0μg、格列本脲5．0μg、4-AP 5．0μg;后4组注射R-PIA 2．0μg前15 min分别注射茶碱5．0μg、DPCPX 1．0μg、格列本脲5．0μg、4-AP 5．0μg,每次给药容积均为0．3μl(用生理盐水稀释)。用热辐射法测定注射R-PIA后5、15、30、45、60、90 min大鼠甩尾反应潜伏期(TFL),痛阈以MPE[(给药后TFL-TFL的基础值)/(10．0-TFL的基础值)×100％]表示。结果脑干网状结构内注射R-PIA 0．5～2．0μg有镇痛作用,且呈剂量依赖性,这种作用可被茶碱和DPCPX完全阻滞,被格列本脲和4-AP部分阻滞。结论脑干网状结构内注射R-PIA对大鼠有一定的镇痛作用,通过作用腺苷A1受体,与开放ATP-敏感型和电压依赖型钾通道有关。
Objective To investigate the analgesic effect and mechanism of adenosine A1 receptor agonist phenylisopropyladenosine (R-PIA) in the reticular formation of brain stem in rats. Methods Sixty male Sprague-Dawley rats were randomly divided into 12 groups (n = 5): control group, R-PIA 0.5 group, R-PIA 1.0 group, R-PIA 2.0 group, theophylline (adenosine receptor blocker) group, DPCPX (adenosine A1 receptor blocker 8-cyclopentylpropylxanthine) group 4-AP (voltage-dependent potassium channel blocker 4-aminopyridine) group, R-PIA2.0 + theophylline group, R-PIA2.0 + DPCPX group, R-PIA2.0 + glyburide group, R-PIA2.0 +4. AP group. The first eight groups were injected with saline, R-PIA 0.5μg, R-PIA 1.0μg, R-PIA 2.0μg, theophylline 5.0μg, DPCPX 1.0μg, glibenclamide 5.0μg, 4-AP and 5.0μg respectively. The last 4 groups were injected with 5.0μg theophylline, 1.0μg DPCPX, 5.0μg glibenclamide and 4-AP 5 before 15min injection of 2.0μg R-PIA. 0μg, each administration volume is 0.3μl (diluted with saline). The rat tail flick reaction latency (TFL) at 5, 15, 30, 45, 60, 90 min after injection of R-PIA was measured by thermal radiation. The pain threshold was calculated as MPE [(basal value of TFL- 10.0-TFL basis value) × 100%]. Results Intravenous injection of R-PIA 0.5-2.0 μg into the reticular structure of the brain stem showed analgesic effect in a dose-dependent manner. This effect was completely blocked by theophylline and DPCPX, and was blocked by glibenclamide and 4- AP partially blocked. Conclusion Intra-brachial injection of R-PIA into the reticular formation of the brain has a certain analgesic effect on rats, which is related to the opening of ATP-sensitive and voltage-dependent potassium channels through the action of adenosine A1 receptor.