摘要
目的探讨小檗碱(BBR)对奥氮平(OLA)诱导的胰岛素抵抗(IR)大鼠炎症因子及TLR4/NF-κB炎症信号通路的影响。方法将36只SD大鼠按照随机数字表法分为对照组、OLA组和OLA+BBR组,每组12只。OLA组大鼠每日腹腔注射OLA 8 mg/kg,OLA+BBR组大鼠给予OLA(腹腔注射)8 mg/kg+BBR(灌胃)200 mg/kg,对照组大鼠腹腔注射等量的无菌生理盐水,连续给药8周。常规记录体重,实验结束时检测空腹血糖(FBG)、空腹胰岛素(Fins)和糖耐量水平。取血清、肝脏和附睾白色脂肪(eWAT)组织,采用ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平。Western blot法检测TLR4、p-NF-κB p65、NF-κB p65、NF-κB抑制蛋白(IκBα)、p-IκBα蛋白表达。结果实验结束时,OLA组大鼠血清FBG、Fins、HOMA-IR高于对照组(P<0.05);且血清、肝脏、eWAT组织中TNF-α、IL-1β、IL-6水平以及TLR4蛋白表达和p-NF-κB p65/NF-κB p65、p-IκBα/IκBα蛋白表达比值较对照组上调(P<0.05)。但是与OLA组相比,OLA+BBR组大鼠上述指标均降低(P<0.05)。结论BBR可明显减缓OLA诱导的IR大鼠模型体重增加速度和炎症反应,可能有助于改善胰岛素抵抗,其作用机制与抑制TLR-4/NF-κB炎症信号通路激活有关。
Objective To investigate the effects of berberine(BBR)on inflammatory factors and TLR4/NF-κB inflammatory signaling pathways in rats with insulin resistance(IR)induced by olanzapine(OLA).Methods Thirty-six SD rats were randomly divided into control group,OLA group and OLA+BBR group,with 12 rats in each group.Rats in OLA group were given intraperitoneal injection of 8 mg/kg OLA,and rats in OLA+BBR group were given 8 mg/kg OLA(intraperitoneal injection)+200 mg/kg BBR(gavage),while rats in control group were given the same amount of sterile saline by intraperitoneal injection,for 8 weeks in a row.Weight was recorded routinely and fasting blood glucose(FBG),fasting insulin(Fins)and glucose tolerance were measured at the end of the experiment.Serum,liver and epididymal white fat(eWAT)tissues were collected and the levels of tumor necrosis factor alpha(TNF-α),IL-1β(IL-1β)and IL-6 were detected by ELISA.Western blot was used to detect the expression of TLR4,p-NF-κB p65,NF-κB p65,NF-κB inhibitor protein(IκBα)and p-IκBαproteins.Results At the end of the experiment,the serum FBG,Fins level and HOMA-IR in OLA group were higher than those in control group(P<0.05),and the levels of TNF-α,IL-1β,IL-6,and the expression of TLR4 protein and the value of p-NF-κB p65/NF-κB p65,p-IκBα/IκBαin serum,liver and eWAT tissues were also up-regulated compared with those in control group(P<0.05).But compared with the OLA group,the above indexes in OLA+BBR group were all decreased(P<0.05).Conclusion BBR can obviously slow down the rate of weight gain and inflammatory reaction in OLA-induced IR rats,and may help to improve insulin resistance,whose mechanism may be related to inhibiting the activation of TLR-4/NF-κB inflammatory signal pathway.
作者
兰建萍
刘守青
谢欣娥
王俊
LAN Jian-ping;LIU Shou-qing;XIE Xin-e;WANG Jun(Department of Psychiatry,Jinhua Second Hospital,Jinhua 321016,China;Logistics Department,Zhejiang University of Traditional Chinese Medicine,Hangzhou 310053,China)
出处
《实用药物与临床》
CAS
2021年第10期887-891,共5页
Practical Pharmacy and Clinical Remedies
基金
金华市科技计划项目(2020-4-063)。
