基于NLRP3/Caspase-1细胞焦亡通路研究金匮肾气丸治疗慢性肾衰竭大鼠的疗效机制  

Study on the Mechanism of Jinkui Shenqi Pills(金匮肾气丸)on Chronic Renal Failure Rats Based on NLRP3/Caspase-1 Signaling Pathway

作　　者：张喜奎[1] 苏明星 宋昱娇 李灵辉[2] 朱为坤[2] ZHANG Xikui;SU Mingxing;SONG Yujiao;LI Linghui;ZHU Weikun(The Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350003,Fujian,China;Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China)

机构地区：[1]福建中医药大学附属第二人民医院,福建福州350003 [2]福建中医药大学,福建福州350122

出　　处：《辽宁中医药大学学报》2024年第10期5-9,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：福建省财政厅财政专项(Χ2021005,Χ2020003)。

摘　　要：目的以NOD样受体蛋白3(nucleotide-binding oligomerization domain-like protein3,NLRP3)/半胱氨酸蛋白酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)细胞焦亡通路为切入点,研究金匮肾气丸改善慢性肾衰竭大鼠的疗效机制。方法将80只7周龄雄性Wistar大鼠以随机的方式抽取正常组和假手术组各20只,其中正常组不行手术干预,假手术组仅行手术剥离双肾被膜;40只造模组大鼠依据文献方法行5/6肾切除术制备慢性肾衰竭模型,4周后将造模组造模成功并存活的34只大鼠随机平均分为金匮肾气丸组17只及模型组17只。其中金匮肾气丸组予金匮肾气丸药液,正常组、假手术组及模型组予等量生理盐水进行灌胃56 d。期间观察大鼠一般情况。第57天取材检测大鼠的红细胞(red blood cell,RBC)、血红蛋白(hemoglobin,Hb)、血清肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)值。并测定左肾组织NLRP3、凋亡相关斑点样蛋白[apoptosis-associ-ated speck-like protein containing caspase recruitment domain(CARD),ASC]、Caspase-1、白细胞介素(interleukin,IL)-18及IL-1β的mRNA及蛋白含量表达情况及肾组织病理形态。结果正常组和假手术组大鼠各项指标无明显差别(P>0.05)。金匮肾气丸组大鼠的RBC、Hb水平相对模型组显著升高(P<0.05)。金匮肾气丸组大鼠的Scr、BUN水平相对模型组显著降低(P<0.05)。金匮肾气丸组大鼠相对于模型组大鼠NLRP3、ASC、Caspase-1、IL-18、IL-1β的mRNA和蛋白表达含量则显著降低(P<0.05),光学显微镜及透射电镜观察显示:正常组及假手术组结构形态正常。金匮肾气丸组大鼠病变程度明显轻于模型组大鼠。结论金匮肾气丸可明显改善CRF大鼠的贫血状态、肾功能情况,升高RBC、Hb水平,降低Scr、BUN水平。金匮肾气丸可明显减轻慢性肾衰竭大鼠炎症反应情况,延缓肾衰竭进展。金匮肾气丸延缓慢性肾衰竭进展的机制可能与抑制NLRP3/Objective Nucleotide-binding oligomerization domain-like protein3(NLRP3)/Cysteinyl aspartate specific proteinase-1(Caspase-1)cell scorch death pathway was used as the entry point to study the therapeutic mechanism of Jinkui Shenqi Pills in improving chronic renal failure rats.Methods A total of 80 cases 7-week-old male Wistar rats were randomly selected from the normal group and 20 from the sham group.The normal group could not receive surgical intervention,and the sham group only received surgical peeling of both renal capsule.40 rats in the model group underwent 5/6 nephrectomy to make chronic renal failure model according to the methods described in the literature.After 4 weeks,34 rats in the model group were randomly divided into 17 rats in the Jinkui Shenqi Pills group and 17 rats in the model group.The Jinkui Shenqi Pills group was treated with Jinkui Shenqi Pills liquid,the normal group,sham group and model group to the amount of normal saline lavage 56 days.The general condition of rats was observed during the period.On the 57th day,red blood cell(RBC),Hemoglobin(Hb),serum creatinine(Scr)and blood urea nitrogen(BUN)values were measured.The NLRP3 and the apoptosis-related speck-like protein containing Caspase recruitment domain(CARD)(ASC)in the left kidney,Caspase-1,interleukin-18(IL-18),and interleukin-1β(IL-1β)mRNA and protein expression,and pathological morphology of kidney tissue were detemined.Results There was no significant difference between normal group and sham group(P>0.05).The levels of RBC and Hb in Jinkui Shenqi Pills group were significantly increased compared with model group(P<0.05).Compared with model group,Scr and BUN levels in Jinkui Shenqi Pills group were significantly decreased(P<0.05).Compared with model group,the mRNA and protein expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1βin Jinkui Shenqi Pills group were significantly decreased(P<0.05).Optical microscopy and transmission electron microscopy showed that the structure and morphology of normal group and sham operation group

关 键 词：金匮肾气丸 慢性肾衰竭 NLRP3/Caspase-1细胞焦亡通路 

分 类 号：R285.5[医药卫生—中药学]