摘要
目的:探讨肿瘤坏死因子样凋亡微弱诱导受体(TWEAK)及其受体成纤维细胞生长因子14(Fn14)在肾间质纤维化(RIF)大鼠肾脏组织中的表达及作用。方法:将24只SD大鼠随机分为假手术组、模型组及给药组,每组8只。模型组和给药组均采用单侧输卵管梗阻(UUO)法建立RIF模型,假手术组仅开腹不结扎。给药组术前1周腹腔注射TWEAK/Fn14抑制剂enavatuzumab(3mg/kg),假手术组和模型组注射等量生理盐水。术后采用苏木精—伊红(HE)染色和Masson染色评价RIF程度,Western blotting法检测TEWAK、Fn14、转化生长因子β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)表达,酶联免疫吸附试验(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)及干扰素-γ(IFN-γ)水平。结果:术后14d,与假手术组比较,模型组显微镜下可见严重RIF,TWEAK、Fn14、TGF-β1、α-SMA表达量及血清TNF-α、IL-1、IFN-γ水平明显升高;经Enavatuzumab干预后,给药组RIF减轻,上述指标水平显著低于模型组,差异均有统计学意义(均P<0.05)。结论:TWEAK/Fn14在UUO致RIF大鼠肾组织中的表达明显上调,可调节α-SMA及TGF-β1蛋白表达,促进炎症反应,进而促进肾纤维化的进展。
Objective：To investigate the expression and significance of tumor necrosis factor-like apoptosisinducing receptor（TWEAK）and its receptor fibroblast growth factor 14（Fn14）in unilateral ureteral obstruction（UUO）-induced renal interstitial fibrosis（RIF）rats.Methods：Twenty-four SD rats were randomly divided into a sham-operation group,a model group and an administration group,with 8 rats in each group.The rats in model group and administration group were subjected to UUO to establish RIF model,and rats in sham-operation group underwent open-chest surgery only without ligation.One week before operation,the administration group rats were intraperitonealy injected with TWEAK/Fn14 inhibitor enavatuzumab（3 mg/kg）,and those in other groups received equal volume of saline.The severity of RIF was assessed by hematoxylin-eosin（HE）staining and Masson staining.The protein expression levels of TEWAK,Fn14,transforming growth factor-β1（TGF-β1）andα-smooth muscle actin（α-SMA）were detected by western blotting.The serum tumor necrosis factor（TNF）-α,interleukin（IL）-1 and interferon（IFN）-γlevels were measured by enzyme-linked immunosorbent assay（ELISA）.Results：After 14 days of surgery,compared with the sham-operation group,the model group rats exhibited severe RIF,and the expressions of TWEAK,Fn14,TGF-β1 andα-SMA as well as the serum levels of TNF-α,IL-1 and IFN-γwere significantly increased.The RIF degree was alleviated after administration of enavatuzumab,and the levels of TWEAK,Fn14,TGF-β1,α-SMA,TNF-α,IL-1 and IFN-γwere markedly improved（P〈0.05）.Conclusion：TWEAK/Fn14 expression was obviously up-regulated in UUO-induced RIF rats.It could modulate the expression ofα-SMA and TGF-β1 and promote inflammation response,thereby facilitating the process of RIF.
作者
梅梅
孙华威
陈秀华
聂晶
康晓明
Mei Mei;Sun Huawei;Chen Xiuhua;Nie Jing;Kang Xiaoming(The First Affiliated Hospital of Jiamusi University,Jiamusi 154002,China)
出处
《广西医科大学学报》
CAS
2018年第10期1331-1335,共5页
Journal of Guangxi Medical University
基金
黑龙江省卫生计生委科研课题资助项目(No.2017-401)
