Objective To evaluate the effect of intracerebroventricular injection of 7-nitroindazole (7-NI) on the depression-like behaviors in normal rats.Methods According to body weights,48 SD rats were randomly divided into normal group,model group,sham-operation group and 7-NI groups at different concentrations (n=8).The model group was treated with chronic and unpredictable mild stress.The 7-NI groups received intracerebroventricular injection with 7-NI solutions at different concentrations,once every 3 days for 3 times in total.The sham-operation group was injected with DMSO of the same volume.The rat behaviors were then subjected to the open field test (OFT).The hippocampal nNOS protein levels were detected by Western blot.Results Compared with the normal group((132.47±31.72) m),the total movement distances of model group ((15.04±8.61) m) and 200 nmol/0.5 μl surgery group((18.18± 11.82) m) decreased significantly (P＜ 0.05).Compared with the model group,such distances of sham-operation group ((107.33±20.35)m) and 7-NI groups(50 nmol/0.5 μl:(138.40±56.85)m,(86.97±36.20)m);100 nmol/0.5 μl:(86.97±36.20)m) increased significantly (P＜ 0.05).The normal group entered the central area significantly more times(2.25±2.05) than model group (0.25±0.46)and 200nmol/0.5μl 7-NI group (0.25± 0.46) did (P＜0.05),and the number of times entering the central area of the model group (0.25±0.46)was significantly lower than that of the sham-operation group (1.00 ± 1.07,P＜ 0.05) and 50 nmol/0.5 μl group (0.75 ± 1.16).Compared with the normal group ((46.53 ±41.16) s),the durations of stay in the central area of model group ((1.27 ± 1.92) s) and 200 nmol/0.5 μl 7-NI group ((1.53 ± 2.90) s) were shortened significantly (P＜0.05).Compared with the model group,the durations of stay in the central area of 100 nmol/0.5μl group ((36.54±67.80) s) was lengthened significantly (P＜ 0.05).Western blotting showed that the hippocampal nNOS protein levels of model group (0.43±0.11) and 200 nmol/0.5μl 7-NI group(0.56±0.08) significantly exceeded that of the normal group (0.04±0.02,P＜0.05).The levels of nNOS in sham-operation group (0.04 ±0.02) and 50 nmol/0.5 μl 7-NI group (0.22± 0.08),which were significantly lower than that of the model group (0.43 ± 0.11,P＜ 0.05),were similar to that of the normal group (0.04 ± 0.02,P＞ 0.05).Conclusion Intracerebroventricular injection 200 nmol/0.5 μl 7-NI solution results in depression-like behaviors and increased the expression of nNOS protein reflexively in rats.%目的 观察侧脑室注射7-硝基吲唑(7-Nitroindazole,7-NI)对正常大鼠抑郁样行为及nNOS蛋白表达的影响.方法 雄性SD大鼠48只按体质量随机分为正常组、模型组、假手术组与不同浓度7-NI侧脑室注射组,每组8只.模型组采用慢性不可预知的温和性应激(Chronic and unpredictable mild stress,CUMS)方法进行造模处理,采用不同浓度的7-NI溶液侧脑室注射,1次/3 d,共3次.假手术组注射等体积二甲基亚砜(DMSO).通过旷场实验测试各组大鼠行为学变化,Western bolt法测定海马nNOS蛋白表达水平.结果 与正常组[(132.47±31.72) m]比较,模型组[(15.04±8.61)m]与200 nmol/0.5μl组[(18.18±11.82)m]大鼠旷场实验运动总距离显著下降(P＜0.05),与模型组比较,假手术组[(107.33±20.35) m]与其余浓度手术组[(138.40±56.85)m,(86.97±36.20)m]大鼠运动总距离显著上升(P＜0.05).与正常组[(2.25±2.05)次]比较,模型组[(0.25±0.46)次]与200nmol/0.5μl组[(0.25±0.46)次]大鼠中心区进入次数显著减少(P＜0.05),与模型组比较,假手术组[(1.00±1.07)次]与50 nmol/0.5μl组[(0.75±1.16)次]大鼠中心区进入次数显著增加(P＜0.05).与正常组[(46.53±41.16)s]比较,模型组[(1.27±2.92)s]与200 nmol/0.5μl组[(1.53±2.90)s]大鼠中心区进入时间均显著缩短(P＜0.05);与模型组比较,100 nmol/0.5μl组[(36.54±67.80)s]大鼠中心区进入时间显著增加(P＜0.05).Western bolt结果显示,模型组(0.43±0.11)与200 nmol/0.5μl组大鼠海马nNOS蛋白表达水平(0.56±0.06)显著高于正常组(0.04±0.02)(P＜0.05),与模型组比较,假手术组(0.04±0.02)与50 nmol/0.5μl组(0.22±0.08)大鼠nNOS蛋白表达水平下降,差异有统计学意义(P＜0.05).结论 侧脑室注射200 nmol/0.5μl浓度7-NI导致大鼠发生抑郁样行为,nNOS蛋白表达反射性增加.
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