大鼠脑内血管紧张素Ⅱ参与吗啡耐受的证据

Evidence for brain angiotensin Ⅱ being involved in morphine tolerance in the rat

给大鼠icv AⅡIgG或saralasin可明显推迟连续6次sc吗啡(6μg/kg)造成的急性吗啡耐受(p<0.01)。给大鼠每日3次sc递增剂量吗啡共注射5d(dl为5 mg/kg,d5为25mg/kg)造成慢性耐受后,icv AⅡIgG(20 mg),可部分翻转吗啡耐受,使吗啡的镇痛作用恢复到耐受前水平的50％(p<0.01)。放免测定表明,连续注射吗啡3或6次的大鼠CSF中AⅡ-ir明显增高,分别高于对照组1.17和1.16倍。连续注射吗啡3或5 d的CSF中A1Ⅱ-ir分别高于对照组1.12和2.85倍。

In order to examine the involvement of brain angiotensin Ⅱ (All)in the development of tolerance to morphine anal-gesia in rats,antibodies against AⅡ (AⅡ IgG)or saralasin,the antagonist of AⅡ,was administered intracerebroventricularly (icv)to prevent the endogenously released AⅡ from activating AⅡ receptors,and the dynamic course of the development of morphine tolerance was monitored.Acute morphine tolerance was induced by 6 successive injections of morphine (6mg/kg,sc)at 2 h intervals; this tolerance could be postponed by icv injection of either AⅡ IgG or saralasin (p<0.05,ANOVA).Chronic tolerance to morphine was achieved by injecting increac-ing doses of morphine (from 5 mg/kg to 25 mg/kg,sc,3 times a day)for 5 d,this chronic morphine tolerance was partially reversed by icv injection of AⅡ IgG (20μg)which brought up the effect of morphine analgesia to 50% of the control level(p<0.01,ANOVA).Radioimmunoassay revealed that the contents of AⅡ-ir in CSF of rats given 3 or 6 successive injections of morphine were both 1.2 fold higher than that of the control groups.Likewise,the contents of AⅡ-ir in CSF of rats subjected to chronic morphine tolerance for 3 and 5 d were 1.1 and 2.8 fold higher than that of control groups,respectively.The results suggest that brain AⅡ plays a significant role in the development of morphine tolerance