Zhang Jie, Wu Xin-min, Zuo Ping-ping
Department of Anesthesiology, Peking University First Hospital, Beijing 100034, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Jun 18;38(3):284-8.
To investigate the recent and permanent effects of pretreatment with midazolam on muscarinic receptor of brain in healthy and scopolamine-treated rats.
(1) In recent effect group, thirty-eight male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=10), midazolam+scopolamine group (Mid+sco, n=10). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco groups were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 4th, 5th, and 6th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while same voluminal physiological saline was administered in Con group and Mid group. (2) In permanent effect group, thirty-six male SD rats were randomly divided into 4 groups: control group (Con, n=9), midazolam group (Mid, n=9), scopolamine group (Sco, n=9), midazolam+scopolamine group (Mid+sco, n=9). On the 1st, 2nd, and 3rd days, Mid group and Mid+sco group were treated with intraperitoneal injection of 50 mg/kg midazolam per day while Con group and Sco group were treated with intraperitoneal injection of the same voluminal physiological saline per day. On the 10th, 11th, and 12th days, Scopolamine 0.8 mg/kg intraperitoneal injection per day was administered in Sco group and Mid+sco group while the same voluminal physiological saline was administered in Con group and Mid group. (3)Then the rats was decapitated and the cerebra cortex and hippocampus were removed. The binding capacity of muscarinic receptor with [3H] QNB were determined. Bmax and Kd of muscarinic receptor in hippocampus were determined by Scatchard analysis in recent effect group.
(1) In recent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group, Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group (P<0.05) and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.01). Kd of muscarinic receptor in hippocampus in Sco group and Mid group were higher than in Con group and Mid+sco group (P<0.01). Bmax of muscarinic receptor in hippocampus was significantly higher in Con group than in Mid group (P<0.05), Sco group and Mid+sco group (P<0.01), which was also higher in Mid group than in Sco group and Mid+sco group (P<0.01), higher in sco group than in Mid+sco group (P<0.05). There was no significant difference of the binding capacity of muscarinic receptor in cortex. (2) In permanent effect group: the binding capacity of muscarinic receptor in hippocampus was significantly higher in Con group and Mid group than in Sco group and Mid+sco group (P<0.01). There was no significant difference of the binding capacity of muscarinic receptor in cortex.
Pretreatment with intraperitoneal injection of 50 mg/kg midazolam for three days had no effect on muscarinic receptor of cortex, but could induce the binding capacity of muscarinic receptor with [3H] QNB and change the density and affinity of muscarinic receptor in hippocampus in healthy and scopolamine-treated rats, yet the changes were not permanent.
探讨咪达唑仑预处理对健康大鼠及东莨菪碱处理大鼠脑内毒蕈碱受体的近期及长期影响。
（1）近期效应组：38只雄性SD大鼠随机分为4组：对照组（Con，n = 9）、咪达唑仑组（Mid，n = 9）、东莨菪碱组（Sco，n = 10）、咪达唑仑+东莨菪碱组（Mid + sco，n = 10）。第1、2、3天，Mid组和Mid + sco组每日腹腔注射50 mg/kg咪达唑仑，Con组和Sco组每日腹腔注射等体积生理盐水。第4、5、6天，Sco组和Mid + sco组每日腹腔注射0.8 mg/kg东莨菪碱，Con组和Mid组注射等体积生理盐水。（2）长期效应组：36只雄性SD大鼠随机分为4组：对照组（Con，n = 9）、咪达唑仑组（Mid，n = 9）、东莨菪碱组（Sco，n = 9）、咪达唑仑+东莨菪碱组（Mid + sco，n = 9）。第1、2、3天，Mid组和Mid + sco组每日腹腔注射50 mg/kg咪达唑仑，Con组和Sco组每日腹腔注射等体积生理盐水。第10、11、12天，Sco组和Mid + sco组每日腹腔注射0.8 mg/kg东莨菪碱，Con组和Mid组注射等体积生理盐水。（3）然后断头处死大鼠，取出大脑皮层和海马。测定毒蕈碱受体与[3H]QNB的结合能力。近期效应组采用Scatchard分析测定海马中毒蕈碱受体的Bmax和Kd。
（1）近期效应组：海马中毒蕈碱受体的结合能力Con组显著高于Mid组、Sco组和Mid + sco组（P < 0.01），Mid组高于Sco组（P < 0.05）和Mid + sco组（P < 0.01），Sco组高于Mid + sco组（P < 0.01）。Sco组和Mid组海马中毒蕈碱受体的Kd高于Con组和Mid + sco组（P < 0.01）。海马中毒蕈碱受体的Bmax，Con组显著高于Mid组（P < 0.05）、Sco组和Mid + sco组（P < 0.01），Mid组高于Sco组和Mid + sco组（P < 0.01），Sco组高于Mid + sco组（P < 0.05）。皮层中毒蕈碱受体的结合能力无显著差异。（2）长期效应组：海马中毒蕈碱受体的结合能力Con组和Mid组显著高于Sco组和Mid + sco组（P < 0.01）。皮层中毒蕈碱受体的结合能力无显著差异。
连续3天腹腔注射50 mg/kg咪达唑仑预处理对皮层毒蕈碱受体无影响，但可诱导健康大鼠及东莨菪碱处理大鼠海马中毒蕈碱受体与[3H]QNB的结合能力，改变毒蕈碱受体的密度和亲和力，不过这些改变并非永久性的。
