弓形虫感染对大鼠记忆力影响及其机制的实验研究

目的观察弓形虫感染对大鼠学习记忆能力和海马组织细胞因子(白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6)水平以及大脑皮层一氧化氮合酶(NOS)活性的影响,探讨其可能机制。方法40只清洁级SD大鼠随机分成4组,即对照组和高、中、低感染剂量的弓形虫感染组(2×107/ml×2ml、2×105/ml×2ml、2×103/ml×2ml)。9周后进行被动回避实验和Morris水迷宫试验,观察弓形虫感染对大鼠的学习记忆能力等行为学变化。放射免疫法检测大鼠海马组织IL-1β、IL-6、TNF-α水平,免疫组化检测NOS活性。结果弓形虫感染对大鼠的记忆获得没有影响,但高、中剂量弓形虫感染组大鼠的记忆消失要早于对照组(P<0.05),低感染剂量组大鼠记忆消失与正常对照大鼠比较,差异无统计学意义(P>0.05)。各感染组大鼠Morris水迷宫测试中逃避潜伏期均明显延长,其距离百分比明显降低(P<0.05)。各感染组大鼠海马组织IL-1β、TNF-α水平明显高于对照组(P<0.05);但IL-6水平与对照组相比差异无显著性(P>0.05)。感染组大鼠大脑皮层NOS阳性细胞数增加。结论弓形虫感染对大鼠的学习记忆能力有影响,其作用机制之一可能与大鼠海马组织IL-1β、TNF-α细胞因子水平升高有关。

Experimental study on the influence on infection with Toxoplasma gondii upon the capacity of learning and memory of rats and its possible mechanism

To investigate the influence of infection with Toxoplasma gondii upon the capacity of learning and memory in rats attempting to explore its possible mechanism,40 SD rats were randomly divided into 4 groups,i.e.3 experimental groups with T.gondii infection and one control group without infection.In the experimental groups of mice,high,middle and low doses of T.gondii(2×103/ml.2×105/ml and 2×107/ml.)were used and 2 ml of different concentration of T.gondii tachyzoites were injected intra-peritoneally into rats.Then,the passive avoidance test and morris water maze test were performed to observe the behavior changes of animals,such as the ability of learning and memory.Meanwhile,the levels of IL-1β.IL-6 and TNF-αin hippocampus of the infected rats were assayed by radioimmunoassay and the activity of NOS was determined by immunohistochemical assay.The experimental results showed that no influence of the T.gondii infection on the ability of memory of rats could be demonstrated,but the loss of ability in memory of rats injected with high or middle doses of T.gondii tachyzoites appeared more early than those of the normal control rats(P<0.05)and no significant difference could be found between rats injected with low dose of parasites and the normal control rats.(P>0.05).The escape latency of rats in T.gondii infection groups was significantly greater than that of the normal control group and the percentage of the distance between quadrants was decreased(P<0.05).Compared with those of the control group,the levels of IL-1β and TNF-α in hippocampus of rats elevated significantly in the T.gondii infection groups(P<0.05),but no significant difference in the level of IL-6 could be demonstrated between the infection groups and the control group(P>0.05).In addition,the number of the NOS-positive cells in the cerebral cortex of the infected rats increased.It is concluded from these observations that infection with T.gondii can induce harmful effects on the ability of learning and memory of rats obviously and its mechanism of action may be related to the elevation of IL-1β and TNF-α levels in hippocampus of rats.