白桦脂醇对脓毒症肾损伤大鼠TLR4/NF-κB信号通路的抑制作用研究  

Inhibitory effect of Betulin on TLR4/NF-κB signaling pathway in rats with SIRS kidney injury

作　　者：刘国荣 郭东风[1] 许磊[1] 陈果 陈雅静 袁晓燕[1] 杭敏[1] 王佩 罗娅娟 LIU Guorong;GUO Dongfeng;XU Lei;CHEN Guo;CHEN Yajing;YUAN Xiaoyan;HANG Min;WANG Pei;LUO Yajuan(Emergency Department,Shanghai Pudong New Area Public Interest Hospital,Shanghai 200135,China)

机构地区：[1]上海市浦东新区公利医院急诊科,上海200135

出　　处：《中国急救复苏与灾害医学杂志》2020年第9期1107-1110,1135,共5页China Journal of Emergency Resuscitation and Disaster Medicine

基　　金：上海市浦东新区公利医院人才培养计划(编号:GLRq2018-03);浦东新区卫生系统重点专科(编号:PWZxk2017-05);浦东新区卫生计生2018年度青年科技项目(编号:PW2018B-03)。

摘　　要：目的探究白桦脂醇对脓毒症肾损伤大鼠Toll样受体4/核转录因子-κB(TLR4/NF-κB)信号通路的抑制作用.方法将60只SD大鼠随机分为对照组、脂多糖(LPS)组、LPS+白桦脂醇(Betulin)A组(5 mg/kg)组和LPS+Betulin B组(10 mg/kg)组,每组15例.大鼠注射LPS用作脓毒症肾损伤模型,在模型建立后立即腹膜内施用白桦脂醇5 mg/kg或10 mg/kg.在电镜下观察染色结果,检测血清尿素氮和肾脏中促炎因子水平.结果相较于对照组,LPS组可见明显肾指数上升(P<0.05),LPS+Betulin A、B两组肾指数均较LPS组下降,仅B组与LPS组差异明显(P<0.05);光镜下,对照组肾小管结构正常,在LPS组中观察到扩张的肾小管、肿胀的上皮细胞和受损的刷状缘,LPS+Betulin A组肾小管没有明显改善,LPS+Betulin B组可见显著肾小管损伤减弱;LPS组BUN、Cr、TNF-α和IL-1β水平均明显高于对照组(P<0.05);相较于LPS组,LPS+Betulin A、B两组上述各指标水平均明显下降(P<0.05),其中LPS+Betulin B组下降更为明显(P<0.05);与对照组相比,LPS组F4/80的表达明显增加,LPS+Betulin A、B两组F4/80水平较LPS组受明显抑制,其中LPS+Betu-lin B组抑制更为明显;相较于对照组,LPS组IκK-α/β和NF-κB p65蛋白表达明显上升(P<0.05),LPS+Betulin A、B两组上述两蛋白表达均减少(P<0.05),其中LPS+Betulin B组下降更为明显(P<0.05).结论白桦脂醇通过抑制TLR4/NF-κB信号通路,抑制炎性因子分泌,从而改善脓毒性肾损伤,为脓毒症治疗提供了一种新的化合物候选.Objective To investigate the inhibitory effect of Betulin on Toll-like receptor 4/nuclear transcription factor-kappa B(TLR4/NF-KB)signal pathway in systemic inlammatory response syndrome(SIRS)with kidney injury rats.Methods Sixty SD rats were randomly divided into control group,LPS group,LPS+Betulin A group(5 mg/kg)and LPS+Betulin B group(10 mgkg),with 15 cases in each group.Rats were injected with LPS as a SIRS model.Betulin was ad-ministered intraperioneally 5 mg/kg or 10 mg/kg immediately after the model was established.Pathological staining was observed under microscope.Serum urea nitrogen,Cr and proinflammatory factor levels in the kidney were mea-sured.Results The renal index in LPS group increased significantly compared with the control group(P<0.05).The re-nal index of LPS+Betulin A and B groups was lower than that of LPS group,only there was a significant difference be-tween LPS group and Group B(P<0.05).Expanded renal tubules,swollen epithelial cells,and damaged brush-like bor-ders were observed in the LPS group.LPS+Betulin B group showed significant reduction in renal tubular injury but not LPS+Betulin A group.The levels of BUN,Cr,TNF-a and IL-1βin the LPS group were signifcantly higher than those in the control group(P<0.05).The levels of above indexes in LPS+Betulin A and B groups were significantly decreased compared with the LPS group(P<0.05).The decrease was more significant in the LPS+Betulin B group(P<0.05).Com-pared with the control group,the expression of F4/80 in LPS group increased signifcantly.The levels of F4/80 in LPS+Betulin A and B groups were significantly inhibited compared with LPS group,especially in LPS+Betulin B group.The expression of IkK-o/B and NF-KB p65 protein in LPS group were increased significantly compared with the control group,(P<0.05).The levels of IKK-a/βB and NF-KB p65 protein were decreased in the LPS+Betulin A and B(P<0.05).The deerease was more significant in the LPS+Betulin B group(P<0.05).Conclusion Betulin can inhibit the expres-sion of inflammatory factors b

关 键 词：白桦脂醇 脓毒症 肾损伤 TLR4/NF-κB信号通路 

分 类 号：R392.9[医药卫生—免疫学]