Neuronal apoptosis in morphine addiction and its molecular mechanism.
Neuronal apoptosis in morphine addiction and its molecular mechanism.
复制标题
DOI：
--
复制
发表时间：
2013-08
影响因子：
0.1
通讯作者：
Li-wei Liu;Jun Lu;Xin-hua Wang;Shu-kun Fu;Quan Li;F. Lin
中科院分区：
文献类型：
--
作者：
Li-wei Liu;Jun Lu;Xin-hua Wang;Shu-kun Fu;Quan Li;F. Lin
目的探讨吗啡成瘾大鼠脑内神经细胞凋亡及其相关蛋白(Fas、Caspase-3和Bcl2)的表达。方法成年雄性SD大鼠48只，体重190~210g，随机分为3组：吗啡成瘾组、吗啡戒断组和对照组，每组16只。成瘾组和戒断组大鼠连续13d腹腔注射吗啡诱导吗啡成瘾。戒断组大鼠以5 mg/kg纳洛酮腹腔注射诱导戒断30min。对照组大鼠注射生理盐水。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测细胞凋亡。免疫组织化学和Western印迹法检测大鼠海马区Fas、Bcl2和Caspase 3的表达。结果与对照组相比，成瘾组和戒断组大鼠脑内神经元凋亡率明显增加(P<0.05)。结论长期使用吗啡可通过上调促凋亡的Fas和Caspase-3的表达，降低抗凋亡的Bcl2的表达，从而诱导脑细胞的凋亡，这可能是阿片类药物致神经元损伤的机制之一。
OBJECTIVE This study aimed to investigate neuronal apoptosis and expression of apoptosis related proteins (Fas, Caspase-3 and Bcl-2) in the brain of rates with morphine addiction. METHODS A total of 48 adult male Sprague-Dawley rats weighing 190-210 g were randomly divided into 3 groups (n=16 per group): morphine addiction group, morphine abstinence group and control group. Rats in the addiction group and the abstinence group were intraperitoneally treated with morphine for 13 days to induce morphine addiction. In abstinence group, rats were then intraperitoneally treated with naloxone at 5 mg/kg to induce abstinence for 30 min. Rats in the control group were injected with normal saline. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptotic cells. Immunohistochemistry and Western blot assay were performed to determine the expressions of Fas, Bcl-2 and Caspase-3 in the hippocampus. RESULTS When compared with the control group, the proportion of apoptotic neurons increased significantly in the addiction group and the abstinence group (P0.05). CONCLUSION Long term use of morphine can induce neuronal apoptosis in the brain by increasing the expressions of pro-apoptotic Fas and Caspase-3 and decreasing the anti-apoptotic Bcl-2 expression, which might be one of mechanisms underlying the opiate-induced neuronal damage.