MCI-186对痴呆模型大鼠认知损害和脑内DNA氧化应激的影响

Effects of MCI-186 on cognitive impairment and DNA oxidative stress in rat model of dementia

摘要:

目的 观察MCI-186对双侧脑室内注射链脲菌素(STZ)诱导的认知损害模型大鼠认知功能和脑内DNA氧化应激的影响.方法 64只成年雄性SD大鼠随机分为4组:假手术组(S)、MCI-186+假手术组(M+S)、模型组(L)和MCI-186+制模组(M+L).跳台试验和水迷宫试验测试大鼠认知功能;比色法和免疫荧光法分别检测大鼠脑内的H₂O₂、CAT含量和8OHdG表达.结果 跳台试验中,与S组比较,L组潜伏期(179.1±41.3)显著缩短(P<0.05),错误次数(3.88±0.87)显著增加(P<0.05);与L组比较,M+L组潜伏期(250.5±27.1)显著延长(P<0.05),错误次数(2.83±0.64)显著减少(P<0.05).Morris水迷宫试验中,与S组比较,L组大鼠潜伏期(36.1±3.59)显著延长(P<0.05);与L组比较,M+L组潜伏期(18.63±3.73)显著缩短(P<0.05).与L组比较,M+L组脑内H₂O₂含量显著减少(P<0.05),CAT活性显著提高(P<0.05),8OHdG表达阳性率显著降低(P<0.05).结论 MCI-186能够改善STZ诱导的大鼠认知损害和脑内DNA氧化应激.

Abstract:

Objective To observe the effects of MCI-186 on the cognitive function and DNA oxidative stress in the rat model of cognitive impairment induced by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ).Methods Sixty-four adult male Sprague-Dawley rats were randomly divided into 4 groups: Sham (S), MCI-186+Sham (M+S), ICV-STZ Lesion (L), and MCI-186+Lesion (M+L). The step-down test was used to evaluate potential deficits in memory retention. Spatial learning and memory were tested using the Morris water maze (MWM). The content of hydrogen peroxide (H₂O₂) and activity of catalase (CAT) in the cerebral cortex and hippocampal neurons were determined by colorimetric method. Immunofluorescence staining was used to measure the expression of 8OHdG.Results In the step-down test, compared with the S group, the L group had a significantly reduced latency (179.1±41.3) but a significantly increased number of errors (3.88±0.87) (P<0.05 for both); compared with the L group, the M+L group had a significantly increased latency (250.5±27.1) but a significantly reduced number of errors (2.83±0.64) (P<0.05 for both). The MWM test showed that the L group had a significantly longer latency (36.1±3.59) than the S group (P<0.05), and the M+L group had a significantly shorter latency (18.63±3.73) than the L group (P<0.05). Compared with the L group, the M+L group had a significantly reduced content of H₂O₂ (P<0.05), a significantly increased activity of CAT (P<0.05), and a significantly decreased positive rate of 8OHdG expression (P<0.05).Conclusions MCI-186 can reduce the STZ-induced cognitive impairment and DNA oxidative stress in rats.