摘要
目的 研究鲜地黄和生地黄对脓毒症急性肾损伤的干预作用及与雌激素之间的关系。方法 120只雄性BALB/c小鼠随机分为正常对照组,拮抗剂对照组,模型组、阳性药组、鲜地黄组、生地黄组以及相对应的+拮抗剂组,每组12只。小鼠以腹腔注射脂多糖(LPS)5 mg·kg^(-1)建立脓毒症急性肾损伤模型,阳性药组、鲜地黄组、生地黄组分别灌胃黄芪注射液4 g·kg^(-1)、鲜地黄水提物溶液10 g·kg^(-1)、生地黄水提物溶液5 g·kg^(-1),其余组灌胃等量蒸馏水,每日1次,连续6 d。+拮抗剂组小鼠在每日给药前0.5 h腹腔注射雌激素受体特异性拮抗剂(ICI 182780)0.5 mg·kg^(-1),其余各组注射等量生理盐水。观察各组肾组织病理变化,检测血清中尿素氮(BUN)、肌酐(Scr)和细胞因子白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-17A、干扰素(IFN)-γ水平,检测原代肾细胞凋亡和活性氧(ROS)水平,检测肾脏中Toll样受体4(TLR4)、caspase-11、NOD样受体热蛋白结构域相关蛋白3(NLRP3)和IL-1β mRNA水平及TLR4/核因子(NF)-κB-信号转导与转录激活因子1 (STAT1)和caspase-11/NLRP3信号通路相关蛋白的表达。结果 与正常对照组相比,模型组小鼠出现肾小球萎缩、肾小管扩张、上皮细胞脱落等肾脏损伤,血清中Scr、BUN水平和细胞因子IL-6、TNF-α、IL-17A、IFN-γ水平显著升高,原代肾细胞ROS和凋亡水平升高,肾脏TLR4、caspase-11、NLRP3和IL-1β mRNA水平升高,相关通路蛋白TLR4、IFN-β、NF-κB p-p65、p-STAT1、caspase-11、NLRP3和IL-1β显著升高,IL-1受体拮抗剂表达水平显著降低(P <0.01)。鲜地黄和生地黄可有效抑制LPS诱导的肾脏损伤,显著降低BUN、Scr、细胞因子及原代肾细胞ROS和细胞凋亡水平,有效调节TLR4/NF-κB-STAT1和caspase-11/NLRP3信号通路的相关基因和蛋白表达水平(P <0.05),上述作用被雌激素受体拮抗剂减弱(P <0.05)。结论 鲜地黄和生地黄可能通过雌激素受体调节TLR4/N
AIM To study the effects of the fresh Rehmannia glutinosa(XD)and dry Rehmannia glutinosa(SD)on septic acute kidney injury(AKI)and their relationship with estrogen.METHODS Totally 120O male BALB/c mice were randomly divided into normal control group,antagonist control group,and model group,positive drug group,XD group,SD group,and corresponding+antagonist(+ICI)group,12 mice per group.AKI model was established in mice by intraperitoneal injection of lipopolysaccharide 5 mg·kg^(-1).The XD group and SD group were administered intragastrically with 10 g·kg^(-1) of XD and 5 g·kg^(-1)of SD aqueous extract solution respectively.The positive drug group was given 4 g·kg^(-1)of Huangqi injection and the other groups were given the same amount of distlled water by gavage,once a day for 6 consecutive days.The mice in+ICI group were intraperitoneally injected with 0.5 mg·kg^(-1) of estrogen receptor specific antagonist(ICI 182780)O.5 h before administration,the other groups were injected with equal dose of normal saline.The pathological changes of kidney were observed,the levels of blood urea nitrogen(BUN),serum creatinine(Scr),cytokines interleukin(IL)-6,tumor necrosis factor(TNF)-α,IL-17A,and interferon(IFN)-were detected,the level of reactive oxygen species(ROS)and cell apoptosis of primary renal cells were determined,and the levels of toll-like receptor 4(TLR4),caspase-1l,NOD-like receptor pyritin domain-associated protein 3(NLRP3)and IL-IβmRNA as well as the expression levels of TLR4/nuclear factor(NF)-kB-signal transducer and activator of transcription 1(STAT1)and caspase-11/NLRP3 signaling pathway related proteins in kidney were detected.RESULTS Compared with the normal control group,the mice in the model group developed renal damage such as glomerular atrophy,tubular dilation,and epithelial cell shedding,the levels of Scr,BUN,and inflammatory factor IL-6,TNF-α,IL-17A and IFN-in serum were significantly increased,the levels of ROS and apoptosis in primary renal cell were increased,the levels of TLR4,caspase-I1,N
作者
张贝贝
曾梦楠
阚玉璇
张钦钦
贾菊芳
刘萌
郭彭莉
王茹
冯卫生
郑晓珂
ZHANG Bei-bei;ZENG Meng-nan;KAN Yu-xuan;ZHANG Qin-qin;JIA Ju-fang;LIU Meng;CUO Peng-li;WANG Ru;FENG Wei-sheng;ZHENG Xiao-ke(College of Pharmacy,He-nan University of Chinese Medicine,Zhengzhou HE-NAN 450046,China;The Engineering and Technology Center for Chinese Medicine Development of He-nan Province,Zhengzhou HE-NAN 450046,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2023年第4期240-248,共9页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家重点研发计划(2017YFC1702800)
河南道地大宗药材种质评价及集约化种植与示范项目(豫财科[2016]149号)
河南省重大科技专项(171100310500)
河南省高层次人才特殊支持计划(ZYQR201810080)。
关键词
地黄
脂多糖类
急性肾损伤
受体
雌激素
Rehmannia glutinosa
lipopolysaccharides
acute kidney injury
receptors,estrogen
