论文部分内容阅读
目的评价归元片对吗啡镇痛以及吗啡所致耐受和痛觉过敏的影响。方法 1吗啡急性耐受模型小鼠每隔1 h分别ig给予归元片200,400和800 mg·kg-1,15 min后sc给予吗啡10 mg·kg-1,连续给9 h,分别于24和48 h再给予吗啡10 mg·kg-1;2吗啡慢性耐受模型小鼠每日ig给予归元片200,400和800 mg·kg-1,15 min后sc给予吗啡10 mg·kg-1,连续给8 d,d 9单独sc给予吗啡10 mg·kg-1;3吗啡已形成耐受模型小鼠每日sc给予吗啡10 mg·kg-11次,连续给8 d,分别于d 1,d 4或d 7起联合给予归元片200 mg·kg-1,d 9再单独sc给予吗啡10 mg·kg-1。采用小鼠热板测定给药前痛阈值(T0)和给药后痛阈值(T1),计算最大可能镇痛率(%MPAE)。采用分光光度法检测脊髓中一氧化氮合酶(NOS)活性和一氧化氮(NO)含量。结果热板实验中归元片镇痛效应的ED50为523.5 mg·kg-1。归元片200和400 mg·kg-1能延长吗啡镇痛时间,并使吗啡镇痛ED50值从4.67 mg·kg-1分别降至3.14和0.65 mg·kg-1。在吗啡急性和慢性耐受模型中,归元片能抑制%MPAE值和给药前痛阈值的降低(P<0.05);在已形成的耐受模型中,归元片能快速逆转已降低的%MPAE值(P<0.05),且当该复方制剂于d 1起与吗啡联用时,能有效抑制吗啡所致脊髓中NOS活性和NO含量的升高(P<0.01)。结论归元片能有效增强吗啡镇痛,延长吗啡镇痛的持续时间,抑制吗啡所致耐受和痛觉过敏的发展,并可能具有神经保护作用。
Objective To evaluate the effect of Gui Yuan Tablet on morphine analgesia and morphine-induced tolerance and hyperalgesia. Method 1 Morphine acutely tolerated mice were treated with 200, 400 and 800 mg · kg-1 of Gui-yuan tablets every 1 h, sc-administered with morphine 10 mg · kg-1 for 15 min and then continuously for 9 h at 24 and 48 h and then given morphine 10 mg · kg-1; 2 morphine-induced chronic morphine mice were given igneous tablets daily doses of 200,400 and 800 mg · kg-1, 15 min after sc administered morphine 10 mg · kg-1, continuous On the 8th day, morphine 10 mg · kg-1 was given to sc alone on d 9, and 3-morphine tolerant mice were sc scalds of morphine 10 mg · kg-11 once daily for 8 days, respectively, on d 1, d 4 or d 7 from the joint tablets were given 200 mg · kg-1, d 9 and then sc alone given morphine 10 mg · kg-1. The pre-dose pain threshold (T0) and post-dose pain threshold (T1) were determined using a mouse hot plate to calculate the maximum possible rate of analgesia (% MPAE). Spectrophotometry was used to detect nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord. Results In the hot plate experiment, the ED50 of the patchy analgesic effect was 523.5 mg · kg-1. Guiyuan 200 and 400 mg · kg-1 could prolong the time of morphine analgesia and reduce ED50 of morphine analgesia from 4.67 mg · kg-1 to 3.14 and 0.65 mg · kg-1, respectively. In the morphine acute and chronic tolerance model, Gui Yuan Chang inhibited the% MPAE value and the decrease of pain threshold before administration (P <0.05). In the established tolerance model, Gui Yuan Tablet can rapidly reverse the decreased % MPAE (P <0.05). When combined with morphine at d 1, the compound could inhibit the increase of NOS activity and NO in spinal cord induced by morphine (P <0.01). Conclusion Guiyuan Tablet can effectively enhance morphine analgesia, extend the duration of morphine analgesia, inhibit the development of morphine tolerance and hyperalgesia, and may have neuroprotective effects.