黄芪甲苷经FXR-NLRP3途径保护顺铂诱导的小鼠肾损伤研究

AstragalosideⅣProtects against Cisplatin-Induced Kidney Injury in Mice via FXR-NLRP3 Pathway

目的探究FXR-NLRP3通路在黄芪甲苷(ASⅣ)减轻顺铂(CDDP)诱导小鼠肾损伤中的作用机制。方法雄性Balb/C小鼠随机分为4组,CDDP组及CDDP+ASⅣ组每2天腹腔注射顺铂注射液(4 mg·kg^(-1)),Con组及ASⅣ组注射同体积氯化钠注射液,CDDP+ASⅣ和ASⅣ组每天灌胃ASⅣ(75 mg·kg^(-1))。通过血清肌酐(Cr)、尿素氮(BUN)水平及肾脏HE染色等方法评价ASⅣ对CDDP诱导小鼠肾损伤的保护作用。采用Western Blot和免疫组化法考察法尼醇X受体(FXR)和Nod样受体蛋白3(NLRP3)蛋白表达情况,并给予FXR选择性抑制剂没药甾酮(GS)验证该通路的作用。结果与CDDP组相比联合ASⅣ可明显降低小鼠Cr与BUN(P<0.05),HE染色结果显示ASⅣ可以明显减轻CDDP造成的肾组织损伤程度。Western Blot和免疫组化结果显示联合ASⅣ后能够上调FXR并抑制NLRP3通路减轻炎症反应,给予GS后,NLRP3的抑制作用部分消失。结论ASⅣ通过激活FXR途径抑制NLRP3蛋白表达,减轻炎症反应,从而减轻CDDP诱导的肾损伤。

OBJECTIVE To explore the effect of astragalosideⅣ(ASⅣ)on cisplatin(CDDP)induced kidney injury in mice via FXR-NLRP3 pathway.METHODS Male Balb/C mice were randomly divided into 4 groups,which were treated with intraperitoneally injected normal saline(Con),intraperitoneally injected CDDP(4 mg·kg^(-1))per two days,intraperitoneally injected CDDP plus oral ASⅣ(75 mg·kg^(-1))daily and ASⅣalone,respectively.Serum creatinine(Cr)and blood urea nitrogen(BUN)levels and tissues hematoxylin-eosin(HE)staining were used to evaluated the degree of kidney injury.The expressions of FXR and NLRP3 protein were assessed by Western blot and immunohistochemical.Moreover,Z-guggulsterone(GS),FXR selective inhibitor,was administered to verify the role of FXR-NLRP3 pathway.RESULTS Compared with CDDP group,CDDP+ASⅣsignificantly reduced Cr and BUN in serum(P<0.05),and HE staining results showed that ASⅣcould allevite injury in kidney.ASⅣcould increase the expression of FXR and inhibit the expression of NLRP3 respectively.GS could inhibit the expression of FXR and then weaken the inhibition of NLRP3 by co-treated with ASⅣand CDDP.CONCLUSION ASⅣcould protect against CDDP-induced kidney injury via FXR-NLRP3 pathway.