和解聚散方对糖尿病肾病大鼠肾脏NF-κB/NLRP3/Caspase-1细胞焦亡通路的影响  

Effects of Hejie Jusan Decotion on NF-κB/NLRP3/Caspase-1 cell pyroptosis pathway in kidney of rats with diabetic nephropathies

作　　者：姚洁琼 崔赵丽[2] Yao Jieqiong;Cui Zhaoli(Department 1 of Nephropathy,Shanxi Provincial Hospital of Traditional Chinese Medicine(Shanxi Provincial Institute of Traditional Chinese Medicine),Taiyuan 030012,China;Nephrology and Endocrinology Department,Tongzhou Campus,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101121,China)

机构地区：[1]山西省中医院(山西省中医药研究院)肾病一科,太原030012 [2]北京中医药大学东直门医院通州院区肾病内分泌科三区,北京101121

出　　处：《国际中医中药杂志》2024年第11期1450-1454,共5页International Journal of Traditional Chinese Medicine

基　　金：山西省中医药管理局科研课题(2022ZYYC002);北京市通州区科技计划项目(KJ2022CX065);山西省中医药研究院院级课题(201802)。

摘　　要：目的探讨和解聚散方对糖尿病肾病(DN)大鼠细胞焦亡的影响,基于NF-κB/核苷酸结合寡聚结构域样受体蛋白3(NLRP3)/Caspase-1信号通路探讨其作用机制。方法将60只SD大鼠按随机数字表法分为空白组、模型组、氯沙坦钾组及和解聚散方低、中、高剂量组,每组10只。除空白组外,其余各组建立DN大鼠模型。和解聚散方低、中、高剂量组分别灌胃0.5、1.0、2.0 g/ml和解聚散方水煎液;氯沙坦钾组灌胃20 mg/kg氯沙坦钾;空白组和模型组灌胃等体积的生理盐水。1次/d,连续给药28 d。测定大鼠血清SCr、BUN水平及尿液24 h尿蛋白定量,采用HE染色观察肾组织病理改变,采用Western blot法检测肾组织P65、NLRP3、Caspase-1、消皮素D(GSDMD)蛋白表达。结果与模型组比较,和解聚散方高剂量组和氯沙坦钾组大鼠血清SCr、BUN及尿液中24 h尿蛋白定量降低(P<0.01),和解聚散方各剂量组和氯沙坦钾组大鼠肾组织中P65、NLRP3、Caspase-1和GSDMD表达降低(P<0.05或P<0.01)。结论和解聚散方可能通过抑制NF-κB/NLRP3/Caspase-1通路的激活,影响细胞焦亡,减轻肾功能损伤及组织病理改变,从而达到治疗DN的作用。Objective To explore the effect of Hejie Jusan Decoction on pyroptosis in diabetic nephropathies(DN)rats;To explore its mechanism based on the NF-κB/nucleotide binding oligomeric domain like receptor protein 3(NLRP3)/Caspase-1 signal pathway.Methods Totally 60 SD rats were divided into blank group,model group,potassium losartan group,and Hejie Jusan Decoction high-,medium-,and low-dosage groups.In addition to the blank group,the other five groups were established DN rat models.Hejie Jusan Decoction high-,medium-,and low-dosage groups were given 0.5,1.0,and 2.0 g/ml concentrations of Hejie Jusan Decoction,respectively;the potassium losartan group was orally administered with 20 mg/kg potassium losartan;The blank group and model group were given equal volumes of physiological saline by gavage,once a day,for consecutive 28 days.After medication,the levels of serum creatinine(SCr),urea nitrogen(BUN),and 24-hour urine protein(24 hUP)were detected;pathological changes in renal tissue were detected by HE staining;Western blot method was used to detect the expressions of P65,NLRP3,Caspase-1,and GSDMD protein in renal tissues.Results Compared with the model group,the SCr,BUN,and 24-hUP of rats in the Hejie Jusan Decoction high-dosage group and the potassium losartan group decreased(P<0.01).The expressions of P65,NLRP3,Caspase-1,and GSDMD protein in renal tissues of Hejie Jusan Decoction groups and potassium losartan group decreased(P<0.05 or P<0.01).Conclusion Hejie Jusan Decotion may affect pyroptosis by inhibiting the activation of NF-κB/NLRP3/Caspase-1 pathway,reducing renal function damage and pathological changes,so as to achieve the effect of treating diabetes nephropathy.

关 键 词：糖尿病肾病 细胞焦亡 和解聚散方 NF-κB/NLRP3/Caspase-1通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]