摘要
目的:探讨亚麻木酚素/开环异落叶松脂素二葡萄糖苷(SDG)对慢性间歇性低氧(CIH)小鼠肾脏炎症损伤的改善作用及潜在机制。方法:将SPF及雄性C57BL/6N小鼠分为正常组、CIH组和SDG治疗组。记录小鼠体重变化;HE染色观察肾脏组织形态;生化检测血清肌酐和血尿素氮的含量;羟胺法和硫代巴比妥酸比色法测定肾脏组织超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量;免疫组织化学检测硫氧还蛋白结合蛋白(TXNIP)和核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)的蛋白表达情况;ELISA法测定肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和IL-1β等促炎因子的含量;Western blot检测TXNIP、NLRP3炎症小体相关蛋白[NLRP3、含CARD的凋亡相关斑点样蛋白(ASC)和caspase-1]、IL-1β和IL-18的蛋白表达情况。结果:3组小鼠的体重和肾脏指数无显著差异(P>0.05)。HE染色显示,CIH组肾小球形态不规则,肾小管上皮细胞肿胀,胞浆模糊,出现轻微的水泡变性,经SDG治疗后有所改善。与正常组相比,CIH组小鼠血清肌酐及炎症因子TNF-α、IL-6和IL-1β的含量显著升高(P<0.05),免疫组织化学染色显示,CIH组肾小管上皮细胞胞浆内NLRP3和TXNIP的表达显著升高(P<0.05),SDG治疗后均显著下降(P<0.05)。与正常组相比,CIH组肾脏组织的SOD活性降低,MDA含量增多(P<0.05),TXNIP、NLRP3、ASC、caspase-1、IL-1β和IL-18的蛋白水平上调,且经过SDG治疗后均显著下降(P<0.05)。结论:亚麻木酚素可减轻CIH小鼠的肾脏炎症损伤,其机制可能与抑制氧化应激和NLRP3炎症小体的激活有关。
AIM:To investigate the effectof flax lignan/secoisolariciresinol diglucoside(SDG)on the inflammatory damage of kidney induced by chronic intermittent hypoxia(CIH).METHODS:C57BL/6N mice were divided into normal(control)group,model(CIH)group and treatment(SDG)group.The changes of the body weight was recorded.Hematoxylin-eosin(HE)staining was used to observe the morphological alterations in the renal tissues.The levels of serum creatinine and blood urea nitrogen were measured by a biochemical analyzer.Hydroxylamine and thiobarbituric acid methods were used to detect the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in the renal tissues.The protein levels of thioredoxin-interacting protein(TXNIP)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)were detected by immunohistochemical staining,while those of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β were measured by ELISA.The protein levels of TXNIP,NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,IL-1β and IL-18 in the renal tissues were also determined by Western blot.RESULTS:No significant difference in the body weight and kidney index among the 3 groups was observed(P>0.05).HE staining showed the swollen epithelial cells of renal tubules with vesicular degeneration,and irregular glomerular morphological change in CIH group,while SDG treatment attenuated the above changes.Compared with control group,the levels of serum creatinine,TNF-α,IL-6 and IL-1β were significantly increased in CIH group(P<0.05).The significantly increased expression levels of NLRP3 and TXNIP in the cytoplasm of renal tubular epithelial cells in CIH group were detected by immunohistochemical staining.Compared with control group,the activity of SOD was decreased,the content of MDA was increased in CIH group,and the protein expression levels of TXNIP,NLRP3,ASC,caspase-1,IL-1β and IL-18 were up-regulated and then decreased after SDG treatment(P<0.05).CONCLUSION:SDG attenuates the renal infla
作者
刘寒
郭亚净
赵亚硕
任静
周健
吉恩生
LIU Han;GUO Ya-jing;ZHAO Ya-shuo;REN Jing;ZHOU Jian;JI En-sheng(Science and Technology Center,Hebei University of Chinese Medicine,Shijiazhuang 050200,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2020年第9期1631-1638,共8页
Chinese Journal of Pathophysiology
基金
河北中医学院省属高校基本科研业务费专项项目(No.YJZ2019005)。
