壳寡糖通过调控SOCS3/STAT3信号通路改善脂多糖诱导的小鼠神经炎症

Chitosan oligosaccharide ameliorates lipopolysaccharide-induced neuroinflammation in mice by modulating the SOCS3/STAT3 signaling pathway

中文关键词:  壳寡糖  LPS  神经炎症  SOCS3/STAT3信号通路

英文关键词:chitosan oligosaccharide  lipopolysaccharide  neuroinflammation  SOCS3/STAT3 signaling pathway

中文摘要:

      目的 探讨壳寡糖(chitosan oligosaccharide, COS)对脂多糖(lipopolysaccharide, LPS)诱导小鼠神经炎症的改善作用及机制。方法 通过对10周龄C57BL/6N小鼠腹腔注射LPS建立神经炎症模型。动物随机分为5组, 分别是: 对照(CON)组、LPS组、LPS+COS低剂量(LPS+COS 50 mg/kg)组、LPS+COS中剂量(LPS+COS 100 mg/kg)组、LPS+COS高剂量(LPS+COS 200 mg/kg)组。LPS注射完毕后进行旷场实验、新物体识别、Morris水迷宫等行为学实验。处死动物后, 收集脑组织, 酶联免疫吸附实验(enzyme linked immunosorbent assay, ELISA)分析脑内促炎因子白细胞介素-2 (interleukin-2, IL-2)、白细胞介素-6 (interleukin-6, IL-6)和抗炎因子白细胞介素-4 (interleukin-4, IL-4)的表达; Western blot分析脑内信号传导及转录激活蛋白(STAT3)、细胞因子信号抑制物(SOCS3)蛋白的表达水平。结果 行为学实验结果表明, COS可以改善LPS诱发的小鼠认知障碍下降等表现。ELISA结果表明, LPS组小鼠的促炎细胞因子的释放量显著增加, 抗炎细胞因子的释放量显著降低; 而COS灌胃可逆转这一变化趋势。Western blot结果提示, 与CON组相比, LPS的STAT3磷酸化水平显著升高, 同时也促进SOCS3的蛋白表达升高; 而COS则显著下调这两个蛋白的表达。结论 COS可能通过抑制SOCS3/STAT3信号通路改善LPS引起的小鼠神经炎症。

英文摘要:

      Objective To investigate the ameliorative effect and mechanism of chitosan oligosaccharide (COS) on lipopolysaccharide (LPS)-induced neuroinflammation in mice. Methods The experiment was conducted to establish a neuroinflammatory model by intraperitoneal injection of LPS into 10-week-old C57BL/6N mice. Animals were randomly divided into five groups: Control (CON) group, LPS group, LPS+COS low dose (LPS+COS 50 mg/kg) group, LPS+COS medium dose (LPS+COS 100 mg/kg) group, and LPS+COS high dose (LPS+COS 200 mg/kg) group to perform behavioral experiments including open field test, new objects recognition, Morris water maze. After mice were sacrificed, the brain tissues were collected and the expression of pro-inflammatory factors interleukin-2 (IL-2), interleukin-6 (IL-6), and anti-inflammatory factors interleukin-4 (IL-4) was analyzed by enzyme linked immunosorbent assay (ELISA). The protein levels of signaling and activation of transcription proteins (STAT3), suppressor of cytokine signaling (SOCS3) were analyzed by Western blot. Results The results of behavioral experiments showed that COS could improve the performance of LPS-induced cognitive impairment in mice. The results of ELISA showed that the release of pro-inflammatory cytokines was significantly increased while the release of anti-inflammatory cytokines was significantly decreased in LPS-treated mice, but the gavage of COS could reverse this trend. The results from Western blot suggested that compared with CON group, the STAT3 phosphorylation level was significantly increased and also promoted the protein expression of SOCS3, while COS significantly down- regulated the expression of these two proteins. Conclusion COS may ameliorate LPS-induced neuroinflammation in mice by inhibiting the activation of the SOCS3/STAT3 signaling pathway.