甜叶菊正丁醇提取物对抑郁小鼠肝脏单一免疫球蛋白白细胞介素1受体相关蛋白和核转录因子κB表达的影响

Influence of Butanol Extract from Stevia on the expression of single immunoglobulin interleukin - 1 receptor - related molecule and nuclear factor kappa -B in depression mice liver

目的对甜叶菊正丁醇提取物（BEFS）进行抗抑郁活性评价，并探讨其可能作用机制。方法将45只小鼠按随机数字表法随机分成正常组、模型组、模型＋氟西汀（Fluoxetine）组、模型＋BEFS-3 g/kg组和模型＋BEFS-6 g/kg组，每组9只。采用慢性不可预知性应激（CUMS）造模3周，通过体质量、水平得分、垂直得分和糖水偏好率行为学指标评估造模是否成功。之后连续灌胃给予BEFS或氟西汀2周，再次行为学检测后处死小鼠，采集肝组织，实时荧光定量PCR检测单一免疫球蛋白白细胞介素1受体相关蛋白（SIGIRR）和核转录因子κB（NF-κB）基因转录。结果造模3周后，模型组体质量、水平得分、垂直得分和糖水偏好率均较正常组显著降低[（17.28±0.49） g比（22.47±0.82） g，P＝0.000；（43.35±1.68）分比（125.25±3.07）分，P＝0.000；（3.92±0.18）分比（15.92±1.78）分，P＝0.000；（49.39±2.05）%比（67.18±4.46）%，P＝0.001]，提示模型建立成功。给药2周后，与模型组体质量[（19.03±0.44） g]、水平得分[（70.50±6.56）分]、垂直得分[（3.08±0.77）分]和糖水偏好率[（41.27±7.59）%]相比，模型＋BEFS-6 g/kg组[（24.42±1.46） g，（99.75±5.07）分，（13.08±1.60）分，（64.31±1.92）%]和模型＋BEFS-3 g/kg组[（23.82±1.72） g，（91.67±5.69）分，（6.92±1.05）分，（59.56±5.31）%]增加，差异均有统计学意义（P均〈0.05）。同时，BEFS能逆转CUMS小鼠SIGIRR基因转录降低和NF-κB基因转录升高（模型＋BEFS-6 g/kg组：1.208 1±0.102 2，1.437 7±0.352 9，P均〈0.05；模型＋BEFS-3 g/kg组：0.768 0±0.108 6，2.186 2±0.203 8，P均〈0.05）。结论BEFS对CUMS抑郁模型小鼠有良好抗抑郁作用，其机制可能与上调肝脏SIGIRR及下调NF-κB相关。

Objective To study the antidepressant -like effect of Butanol Extract from Stevia （BEFS）and its possible corresponding mechanisms. Methods Forty - five mice were randomly divided into control group, model group, model ＋ Fluoxetine group, model ＋ BEFS - 3 g/kg group and model ＋ BEFS - 6 g/kg group. The chronic unpre- dictable mild stress（CUMS） for 3 weeks was used to make up depressive animal model. It was based on body weight, crossing numbers, rearing numbers and sucrose preference to assess whether the model was a success. After continuous lavage giving BEFS and fluoxetine for 2 weeks and subsequent behavioral test, the mRNA transcription of Single immunoglobulin intedeukin - 1 receptor - related molecule（SIGIRR） and nuclear factor kappa - B（ NF - κB） in liver tissue of mice were detected by using quantitative real time - PCR. Results Three weeks after CUMS, behavior parameters were significantly decreased in mice exposed to CUMS compared with control group [ （ 17.28 ± 0.49 ） g vs （22.47 ± 0. 82） g,P=0.000;（43.35 ±1.68） scores vs（125.25 ±3.07） scores,P =0.000;（3.92 ±0.18） scores vs （15.92± 1.78 ） scores, P = 0. 000 ; （49.39 ± 2.05 ） % vs （67.18 ± 4.46 ） %, P = 0.001 ]. However, 2 weeks after dosing, body weight, crossing numbers, rearing numbers and sucrose preference were （ 19.03± 0.44） g, （70.50 ± 6.56 ） scores, （3.08 ± 0.77） scores and （41.27 ±7. 59）%, respectively in model group. Compared to model group, behavior para- meters of BEFS （ 3 and 6 g/kg BEFS） groups were significantly increased [ BEFS - 6 g/kg group ： （24.42 ±1.46） g, （99.75 ± 5.07 ） scores, （ 13.08 ± 1.60 ） scores, （ 64.31 ± 1.92 ） %, all P 〈 0.05 ; BEFS - 3 g/kg group： （ 23.82±1.72） g, （91.67 ±5.69） scores, （6.92 ± 1.05 ） scores, （59.56±5.31 ） %, respectively, all P 〈 0.05 ]. Correspondingly, BEFS could reverse the mRNA expression of SIGIRR lowering and NF - κB rising in the liver of mice exposed to CUMS（BEFS - 6 g/kg group ： 1. 208 1 ±0. 102 2,1. 437 7 ± 0. 352 9 ; BEFS - 3 g/kg group ： 0. 768 0 ±0. 108 6, 2.186 2 ~ 0. 203 8, all P 〈 0. 05 ）. Conclusions BEFS can remarkably improve depression - like behaviors in CUMS mice and its antidepressant activity is mediated, at least in part, by upregulating SIGIRR and downregulating NF - κB in the liver.