黄连素对脂多糖诱导小鼠抑郁样行为及脑内炎症因子的影响

Effects of berberine on lipopolysaccharide induced depressive-like behavior and brain neuroinflammation in mice

目的研究黄连素对脂多糖(lipopolysaccharide,LPS)诱导的小鼠抑郁样行为及脑内白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)含量的影响。方法 50只雄性成年昆明小鼠按照随机数字表法分为生理盐水对照组、LPS组、黄连素低剂量组、黄连素中剂量组、黄连素高剂量组,每组10只。低、中、高剂量黄连素组小鼠分别予以黄连素25、50、100 mg/kg连续灌胃7 d,然后与LPS组小鼠予以腹腔注射LPS 0.83 mg/kg,24 h后进行行为学及海马、前额叶皮层IL-1β、TNF-α含量测定。结果 LPS组小鼠出现明显抑郁样行为,表现为糖水摄入量[(41.0±14.8)%]低于对照组[(75.7±9.0)%](t=5.52,P<0.01),强迫游泳不动时间[(158.7±31.1)s]与对照组[(101.2±29.2)s]比较显著增加(t=4.34,P<0.01)。50,100 mg/kg黄连素灌胃增加了小鼠糖水摄入量,分别为(67.1±15.4)%和(72.0±13.1)%,与LPS组比较差异有统计学意义(t=4.15,P<0.01;t=4.93,P<0.01)。50 mg/kg黄连素组小鼠强迫游泳不动时间为(119.4±26.3)s,较LPS组显著减少(t=2.44,P<0.05);100 mg/kg黄连素组小鼠强迫游泳不动时间[(109.7±21.9)s]也明显低于模型组(t=3.69,P<0.01)。脂多糖注射后小鼠前额叶皮层及海马IL-1β、TNF-α的表达明显上调,三种剂量黄连素均可降低海马和前额叶皮层IL-1β、TNF-α的含量。结论黄连素能显著改善脂多糖所致小鼠抑郁样行为,可能与下调前额叶皮层及海马IL-1β、TNF-α的表达有关。

Objective To observe the effects of berberine on lipopolysaccharide (LPS) induced depressive-like behavior and changes of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in hippocampus and prefrontal cortex of mice. Methods Fifty male Kunming adult mice were randomly divided into control group, LPS group, low dosage berberine group, middle dosage berberine group and high dosage berberine group (n=10 per group). The mice in the later three groups were respectively administrated 25, 50 and 100mg/kg berberine by gavage for 7 days.Then, the later four groups mice were injected LPS intraperitoneally(0.83 mg/kg). Twenty-four hours after LPS injection, the depressive like behavior were observed and level of IL-1β and TNF-α in hippocampus and prefrontal cortex were measured. Results Compared with control group (sucrose intake:(75.7±9.0)%, immobility time:(101.2±29.2) s), the sucrose intake of LPS group((41.0±14.8)%) reduced(t=5.52, P<0.01) and the immobility time ((158.7±31.1) s) in forced swimming test increased(t=4.34, P<0.01). The 50 mg/kg and 100 mg/kg berberine intragastric administration significantly improved sucrose preference ((67.1±15.4)% and (72.0±13.1)%) compared with that in LPS group (t=4.15, P<0.01;t=4.93, P<0.01));and decreased immobility time in forced swimming test ((119.4±26.3) s and (109.7±21.9)s) compared with that in LPS group((t=2.44, P<0.05;t=3.69, P<0.01)). The level of IL-1β and TNF-α in hippocampus and prefrontal cortex significantly increased in LPS group compared with those in control group, while significantly decreased in low, middle and high dosages berberine injected mice compared with those in LPS group. Conclusion Berberine can improve LPS induced depressive-like behavior in mice, and these effects may correlate with decreased level of IL-1β and TNF-α in hippocampus and prefrontal cortex.