异丙酚调控TGF-β1/smads信号通路对UUO诱导的肾纤维化小鼠的保护作用  

Protective effect of propofol on UUO induced renal fibrosis via TGF-β1/Smads signal pathway in mice

作　　者：李颖[1] 张振 赵博[1] 刘亚庆 周南 LI Ying;ZHANG Zhen;ZHAO Bo;LIU Ya-qing;ZHOU Nan(Department of Anesthesiology,Dalian Central Hospital,Dalian 116033;Department of Acute Abdominal Surgery,the Second Affiliated Hospital of Dalian Medical University,Dalian 116023;Department of Anesthesiology,General Hospital of the Northern Theater Command,Shenyang 110016,China)

机构地区：[1]大连市中心医院麻醉科,辽宁大连116033 [2]大连医科大学附属第二医院急腹症外科,辽宁大连116023 [3]北部战区总医院麻醉科,辽宁沈阳110016

出　　处：《解剖科学进展》2020年第6期664-667,672,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180551091)。

摘　　要：目的利用单侧输尿管梗阻(UUO)模型探讨异丙酚(Propofol,PPF)调控转化生长因子-β1(TGF-β1)/Smads信号通路对肾纤维化的保护作用。方法采用UUO的方法造成肾纤维化小鼠模型,将造模成功的小鼠随机分为模型组,PPF高、低剂量组(分别腹腔注射PPF 25 mg/kg、50 mg/kg,连续14天),另取正常C57BL/6小鼠作为假手术组。试剂盒检测各组小鼠血清中Scr和BUN含量;HE染色观测各组小鼠肾损伤情况;ELISA法检测各组小鼠损伤肾脏组织中IL-1β、IL-6和TNF-α炎性因子的表达量;qPCR法检测各组小鼠损伤肾脏组织中TGF-β1、smad 2和smad 3 mRNA的表达;Western blot法检测各组小鼠损伤肾脏组织中TGF-β1、(p-)smad 2和(p-)smad 3蛋白水平的表达。结果与假手术组相比,模型组小鼠血清中Scr和BUN含量明显升高,肾小管结构遭到严重的破坏,促炎因子IL-1β、IL-6及TNF-α浓度明显升高,TGF-β1、(p-)smad 2和(p-)smad 3mRNA和蛋白水平表达显著升高。与模型组相比,低高剂量的PPF治疗后,Scr和BUN含量明显降低,肾小管损伤的结构得到改善,降低IL-1β、IL-6和TNF-α蛋白含量,抑制TGF-β1、(p-)smad 2和(p-)smad 3 mRNA和蛋白水平表达。结论PPF显著改善UUO小鼠的肾功能,明显减少肾间质炎性细胞浸润及纤维组织增生,降低炎性因子的释放,与抑制TGF-β1/Smad信号通路相关。Objective To investigate the protective effect of propofol(PPF)on renal fibrosis by using unilateral ureteral obstruction(UUO)model via transforming growth factor-β1(TGF-β1)/Smads signaling pathway.Methods The models of renal fibrosis were established by UUO and randomly divided into model group,high dose group(50 mg/kg PPF,intraperitoneally for 14 days)and low dose group(25 mg/kg PPF,intraperitoneally for 14 days),normal C57 BL/6 mice as sham operation.The levels of Scr and BUN in serum were detected by the kit,HE staining was used to observe the renal injury of mice,the expression of IL-1β,IL-6 and TNF-αin renal tissue was detected by ELISA.The expression of TGF-β1,Smad 2 and Smad 3 mRNA was detected by qPCR,expression of TGF-β1,p-smad 2 and p-smad 3 protein was detected by Western blot.Results The serum levels of Scr and BUN were significantly higher,the renal tubular structure was severely damaged,concentrations of IL-1β,IL-6 and TNF-α,levels of TGF-β1 and(p-)Smad 2 and(p-)Smad 3 mRNA and protein were significantly higher in the model group than in sham operation.The content of Scr and BUN,the level of IL-1β,IL-6 and TNF-αprotein were decreased,and expression levels of TG-β1 and(p-)Smad 2 and(p-)Smad 3 mRNA and protein were downregulated in low-dose and high-dose PPF model groups than in model group.Conclusion PPF significantly improved the renal function,reduced the infiltration of inflammatory cells and the proliferation of fibrous tissue,and reduced the release of inflammatory factors,which is related to inhibiting TGF-β1/Smad signal pathway in UUO mice.

关 键 词：异丙酚 UUO 肾纤维化 炎症因子 TGF-β1/smads信号通路 小鼠 

分 类 号：R691[医药卫生—泌尿科学]