l-四氢巴马汀对羟考酮依赖大鼠神经元损伤的保护作用

Protection of l-Tetrahydropalmatine on Oxycodone Induced Neronal Damage in Rats

目的探讨羟考酮依赖引起大鼠海马CA1区和中脑腹侧被盖区(VTA)内神经元的损伤情况,以及l-四氢巴马汀(l-THP)对羟考酮依赖大鼠神经元损伤的保护作用。方法采用连续递增给羟考酮建立依赖模型:大鼠连续给药22 d,每天2次,从第1天到第8天,从开始剂量2 mg.kg–1,每日递增1 mg至第8天固定为9 mg.kg–1,直到第22天。l-THP伴随给药,l-THP灌胃给药40 min后给羟考酮。末次给药24 h后,取脑,石蜡切片,采用ABC法测海马CA1区和VTA内GFAP的免疫组织化学反应,以其阳性神经元的平均吸光度值表示其含量。结果羟考酮引起大鼠海马CA1区和VTA内GFAP含量明显升高,提示羟考酮能造成神经元损伤。l-THP(15,30 mg.kg–1)抑制海马CA1区和VTA内GFAP含量的升高。结论长期大剂量给予羟考酮能造成大鼠神经元损伤,l-THP对羟考酮依赖大鼠神经元损伤有保护作用。

OBJECTIVE To investage effects of l-tetrahydropalmatine on neuron damage induced by oxycodone in rats. METHODS Rats were administered for 22 consecutive days with oxycodone, twice every day. Oxycodone was increased progressively at the oringinal dose of 2 mg·kg^-1 frome 1st day to 8th day, then, given at the dose of 9 mg·kg^-1 from 8th day to 22nd day. l-THP was administrated 40 min before treatment of oxycodone. The levels of glial fibrillary acidic protein （GFAP） were determined as immunohistochemical intensity. RESULTS Content of GFAP induced by oxycodone was increased in the CAland VTA or NAc region.l-THP decreased content of GFAP in the CA1 or VTA region. CONCLUSION Impairment of heron was induced by oxycodone in rats. l-THP could inhibit the damage, which suggested that l-THP might be benefit for clinical use to prevent oxvcodone-dependence.