白藜芦醇抑制NLRP3炎性小体介导的细胞焦亡信号通路改善肥胖小鼠认知功能

目的 观察白藜芦醇(RES)对肥胖小鼠认知功能的保护作用，并探讨其海马组织核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体—细胞焦亡信号通路机制。方法 50只小鼠随机均分为：正常对照组、模型组和白藜芦醇高(100 mg/kg)、中(50 mg/kg)、低(25 mg/kg)剂量组，喂养6个月后，检测小鼠认知功能，海马组织细胞焦亡水平，海马组织沉默信息调节因子1(SIRT1)、NLRP3、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、白细胞介素-1β(IL-1β)、IL-18和肿瘤坏死因子-α(TNF-α)等蛋白表达情况。采用单因素方差分析或重复测量方差分析进行结果分析。结果 与模型组比较，白藜芦醇高剂量组小鼠终体质量降低(t=-14.453,P=0.021),海马组织细胞焦亡水平降低(t=-17.328,P=0.011),学习记忆能力改善，海马组织SIRT1蛋白表达升高(t=32.812,P<0.001),NLRP3、Caspase-1、IL-1β、IL-18和TNF-α蛋白表达均下降(t=-28.462,P=0.003;t=-38.148,P<0.001;t=-...

Resveratrol ameliorated cognitive function of diet- induced obesity mice through inhibiting pyroptosis mediated by NLRP3 inflammasome

Objective To explore the effects of resveratrol (RES) on the cognitive capability and the expression of the proteins related to the Nod-like receptor protein 3 (NLRP3) inflammasome-pyroptosis signal pathway in hippocampus of diet- induced obesity mice. Methods 50 mice were randomly divided into 5 groups (n=10): normal diet group (CON group), high-calorie diet group (HCD group), HCD+100 mg/kg RES group (H-RES group), HCD+50 mg/kg RES group (M-RES group) and HCD+25mg/kg RES group (L-RES group). After 6 months feeding, the cognitive function of mice, the pyroptosis and silent information regulator 1 (SIRT1), NLRP3, Caspase-1, IL-1β, IL-18 and TNF-α expressions in hippocampus were detected. Results were compared by the One-Way ANOVA or repeated measure ANOVA. Results Compared with HCD group, the final body mass were significantly decreased (t=-14.453, P=0.021), the level of pyroptosis in hippocampus were significantly decreased (t=-17.328, P=0.011), the learning and memory ability were significantly improved and the protein expression of SIRT1 in hippocampus was significantly increased (t=32.812, P＜0.001), while the protein expressions of NLRP3、Caspase-1、IL-1β、IL-18 and TNF-α were significantly decreased (t=-28.462, P=0.003; t=-38.148, P＜0.001; t=-38.809, P＜0.001; t=-47.239, P＜0.001; t=-48.811, P＜0.001) in H-RES group. The final body mass, the level of pyroptosis in hippocampus, the learning and memory ability and the protein expression of SIRT1, NLRP3, Caspase-1, IL-1β, IL-18 and TNF-α were not statistically different (t=12.012, P=0.132; t=-14.252, P=0.104; t=-19.219, P=0.083; t=-7.252, P=0.512; t=-15.252, P=0.286; t=-21.252, P=0.068) in L-RES group. Conclusion RES has concentration effect, and it can prevent diet- induced obesity in the mice and ameliorate cognitive function of the mice through increasing the expression of SIRT1 and inhibiting the activation of NLRP3 inflammasome-pyroptosis signal pathway in hippocampus.