基于LIGHT/HVEM通路研究白藜芦醇对子痫前期大鼠肾损伤的保护作用研究  

Protective effect of resveratrol on renal injury in rats with preeclampsia based on LIGHT/HVEM pathway

作　　者：符海内 汪洪林 张林静[1] 张蕾 符大天 FU Hainei;WANG Honglin;ZHANG Linjing;ZHANG Lei;FU Datian(Department of Obstetrics and Gynecology,Hainan Maternal and Child Health Hospital(Hainan Women and Children Medical Center),Haikou 570206;China.2.Department of Pharmacy,Hainan Maternal and Child Health Hospital(Hainan Women and Children Medical Center),Haikou 570206;.3.Departement of Pharmacy,the First Affiliated Hospital of Hainan Medical University,Haikou 570102)

机构地区：[1]海南省妇幼保健院(海南省妇女儿童医学中心)妇产科,海口570206 [2]海南省妇幼保健院(海南省妇女儿童医学中心)药剂科,海口570206 [3]海南医学院第一附属医院药剂科,海口570102

出　　处：《中国比较医学杂志》2021年第6期77-82,共6页Chinese Journal of Comparative Medicine

基　　金：海南省重点研发计划项目(ZDYF2017093)。

摘　　要：目的探讨白藜芦醇(RSV)对子痫前期(PE)大鼠淋巴毒素类似物(LIGHT)/疱疹病毒介入体(HVEM)通路的影响,及对肾损伤的保护作用。方法将50只SD孕鼠随机分为正常孕鼠组(Normal组)、子痫前期模型组(PE组)、白藜芦醇(RSV)低(50 mg/kg)、高(200 mg/kg)剂量组、LIGHT/HVEM通路阻断剂(淋巴毒素β受体,LTβR-Ig融合蛋白,1600μg/kg,LTβR-Ig组),每组10只。除Normal组外,其余各组大鼠腹腔注射亚硝基左旋精氨酸甲酯(L-NAME,300 mg/kg,共5 d,每天1次)建立大鼠子痫前期模型,造模成功后开始给药,RSV各剂量组灌胃给予相应剂量RSV溶液,LTβR-Ig组经尾静脉注射LTβR-Ig溶液,Normal组和PE组灌胃+尾静脉注射给予等量生理盐水,各组连续给药5 d,每天1次。末次给药后收集大鼠24 h尿液,并取血液,酶联免疫吸附(ELISA)试剂盒检测肾功能指标血清肌酐(Scr)、血尿素氮(BUN)及尿液中24 h尿蛋白量;苏木精-伊红(HE)染色检测各组大鼠肾组织病理变化;实时荧光定量聚合酶链式反应(qRT-PCR)检测肾组织LIGHT、HVEM mRNA相对水平;蛋白免疫印迹法(Western blot)检测肾组织LIGHT、HVEM、核转录因子-κB(NF-κB)、白细胞介素-6(IL-6)蛋白相对表达水平。结果与Normal组相比,PE组大鼠出现肾小球内皮细胞弥漫性增生等病理损伤,血清Scr、BUN及尿液中24 h尿蛋白量、肾组织LIGHT mRNA及蛋白、HVEM mRNA及蛋白、NF-κB、IL-6蛋白表达升高(P<0.05);与PE组相比,RSV低、高剂量组、LTβR-Ig组大鼠肾组织病理损伤缓解,血清Scr、BUN及尿液中24 h尿蛋白量、肾组织LIGHT mRNA及蛋白、HVEM mRNA及蛋白、NF-κB、IL-6蛋白降低(P<0.05),且RSV高剂量组上述指标变化均优于RSV低剂量组;LTβR-Ig组上述指标变化与RSV高剂量组相比差异不明显(P>0.05)。结论RSV可抑制PE大鼠肾组织LIGHT/HVEM通路蛋白表达,改善PE肾损伤。Objective To investigate the effect of resveratrol(RSV)on the lymphotoxin analog(LIGHT)/herpesvirus entry mediator(HVEM)pathway in rats with preeclampsia(PE)and its protective effect on kidney injury.Methods Fifty pregnant Sprague-Dawley rats were randomly divided into 5 groups of 10 rats each:the normal group,PE model group,RSV low dose group(50 mg/kg),RSV high dose group(200 mg/kg),and LIGHT/HVEM pathway blocker group(lymphotoxin beta receptor-immunoglobulin fusion protein[LTβR-Ig],1600μg/kg).All rats except those in the normal group were intraperitoneally injected with nitroso-L-arginine methyl ester(300 mg/kg,once daily for 5 days)to establish a rat model of PE.After successful establishment of the model,RSV solution was given by gavage to the rats in the RSV low and high dose groups,LTβR-Ig solution was injected via the tail vein to the rats in the LIGHT/HVEM pathway blocker group,and the same amount of normal saline was given by gavage and tail vein injection to the rats in the Normal and PE groups.Each group was treated once a day for 5 consecutive days.After the last administration,24-hour urine was collected and blood samples were obtained,and the serum creatinine(Scr),blood urea nitrogen(BUN),and 24-hour urinary protein were measured as renal function indices using enzyme-linked immunosorbent assay.Hematoxylin-eosin staining was used to detect the pathological changes of renal tissue.Real-time fluorescent quantitative polymerase chain reaction was used to detect the relative levels of LIGHT and HVEM mRNA in renal tissue.Western blot was used to detect the relative expression levels of LIGHT,HVEM,nuclear factor kappa B(NF-κB),interleukin-6(IL-6)in renal tissue.Results Compared with the rats in the Normal group,those in the PE group exhibited pathological damage such as diffuse proliferation of glomerular endothelial cells and higher levels of Scr,BUN,24-hour urine protein,renal tissue LIGHT mRNA and protein,HVEM mRNA and protein,and NF-κB and IL-6 protein expressions(P<0.05).Compared with the PE gro

关 键 词：白藜芦醇 子痫前期 肾损伤 淋巴毒素类似物/疱疹病毒介入体 

分 类 号：R-33[医药卫生]