ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2022, Vol. 31 ›› Issue (4): 323-327.DOI: 10.3969/j.issn.1006298X.2022.04.005

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白杨素对MRL/lpr狼疮小鼠的保护作用及机制研究

  

  • 出版日期:2022-08-29 发布日期:2022-08-26

The protective effect and mechanism of chrysin on MRL/lpr lupus mice

  • Online:2022-08-29 Published:2022-08-26

摘要: 目的:基于临床疗效确切的“多靶点”疗法(MT)及其前期疗效机制研究,探究白杨素(CHR)对狼疮性肾炎(LN)的疗效及其对白细胞介素6(IL6)/信号传导蛋白和转录激活物3(STAT3)信号通路的影响。
方法:将12只10周龄MRL/lpr狼疮小鼠随机分为疾病组及CHR治疗组,正常对照组采用C57BL/6小鼠,每组6只。CHR治疗组给予CHR 160 mg/(kg·d)灌胃,MRL/lpr组和NC组给予等量羧甲基纤维素钠(CMCNa)灌胃,持续给药8周后处死小鼠,称量脾脏重量,评估脾脏指数;酶联免疫吸附测定(ELISA)实验检测尿蛋白/肌酐水平,过碘酸雪夫(PAS)染色评估肾组织病理损伤程度;实时荧光定量PCR(RTqPCR)和ELISA检测IL6的表达和分泌水平,蛋白免疫印迹(Western Blot)和免疫组化染色(IHC)评估肾组织中STAT3蛋白的磷酸化水平。
结果:CHR治疗可下调MRL/lpr狼疮小鼠脾重及脾脏指数、抑制尿蛋白/肌酐水平并缓解肾脏病理损伤。此外CHR能够显著抑制IL6分泌、表达水平及肾组织pSTAT3蛋白表达。
结论:CHR对 MRL/lpr狼疮小鼠具有保护作用,其机制可能与抑制 IL6/STAT3信号通路有关。


Abstract: Objective:The purpose of this study was to explore the efficacy of chrysin(CHR) on lupus nephritis (LN) and its effects on interleukin6(IL6)/signaling protein and transcriptional activator 3(STAT3) based on the clinically effective “multitarget” therapy and its early efficacy mechanism signaling pathway. 
Methodology:We randomly divided 10weekold MRL/lpr lupus mice into disease group and CHRtreated group. C57BL/6 mice were used as normal control (NC), with 6 mice in each group. The CHR group was given CHR 160 mg/(kg·d) by gavage, the MRL/lpr group and NC group were given the same amount of carboxymethylcellulose sodium (CMCNa) by gavage, and all the mice were sacrificed after continuous administration for 8 weeks. The spleen and renal tissue of mice in different groups were collected for testing. The spleen weight and the spleen index were evaluated. And the pathological changes of kidney tissue were observed by PAS staining; ELISA was performed to detect the urine protein/creatinine level and the serum interleukin6 (IL6) level; IL6 mRNA and PSTAT3 protein expressions in kidney was evaluated by qPCR、western blot and IHC staining.
Results:Our results found that CHR treatment could alleviate spleen weight and spleen index. Furthermore, CHR can downregulate urinary protein/creatinine levels as well as the pathological damage of renal tissue. The circulating IL6 secretion levels and IL6、pSTAT3 expressions in kidney were also inhibited by CHR.
Conclusion:In conclusion, our work found that CHR may have a protective effect in MRL/lpr lupus mice by inhibiting IL6/STAT3 signaling, providing a reference for the development of new LN drugs.


Key words: chrysin,lupus nephritis,interleukin-6