芹菜素通过调节NOS/cGMP/PKG信号通路改善慢性肾脏病大鼠的肾功能OA
Apigenin Improves Renal Function in Rats with Chronic Kidney Disease by Modulating the NOS/cGMP/PKG Signaling Pathway
目的:探究芹菜素对慢性肾脏病(CKD)大鼠肾功能的改善作用及对一氧化氮合酶(NOS)/环磷酸鸟苷(cGMP)/蛋白激酶 G(PKG)信号通路的影响.方法:将 60 只雄性 SD 大鼠随机分为对照组、模型组、阳性药物缬沙坦、芹菜素低、中、高剂量组,每组 10 只.150mg·kg-1·d-1 的 0.25%腺嘌呤溶液连续灌胃8 周以构建 CKD 大鼠模型.检测各组大鼠的肾组织重量,全自动生化检测仪测定大鼠血清中肌酐(SCr)、尿素氮(BUN)、尿酸(UA)、IL-6、IL-1β、TNF-α 的水平及 24h 尿蛋白定量(24h UTP),HE 染色、Masson 染色分别检测肾组织的病理学损伤及纤维化程度,Western blot 检测肾组织中LC3、Beclin1、p62、PKG 蛋白的表达,试剂盒检测肾组织中 NOS、一氧化氮(NO)、cGMP 蛋白的水平.结果:相对于对照组,模型组大鼠的肾组织重量、SCr、BUN、UA、24h UTP、p62、IL-6、IL-1β、TNF-α 升高(P<0.05),LC3Ⅱ/Ⅰ比值、Beclin1、NOS、NO、cGMP、PKG 降低(P<0.05),肾组织呈现显著的显著的病理学损伤及纤维化病理改变;相对于模型组,阳性药物组、芹菜素低、中、高剂量组大鼠的肾组织重量、SCr、BUN、UA、24h UTP、p62、IL-6、IL-1β、TNF-α 降低(P<0.05),LC3Ⅱ/Ⅰ比值、Beclin1、NOS、NO、cGMP、PKG 升高(P<0.05),肾组织的病理学损伤及纤维化程度减轻;芹菜素的作用效果呈剂量依赖性(P<0.05).结论:芹菜素能够通过促进自噬、抑制炎症反应来抑制肾组织病理损伤及纤维化,改善 CKD 大鼠肾功能,其机制可能与激活 NOS/cGMP/PKG 信号通路有关.
Objective:To explore the improving effect of apigenin on renal function in rats with chronic kidney disease(CKD)and its effects on nitric oxide synthase(NOS)/cyclic guanosine phosphate(cGMP)/protein kinase G(PKG)signaling pathway.Methods:Sixty male SD rats were randomly divided into control group,model group,positive drug valsartan,and low-,medium-,and high-dose apigenin groups,with 10 rats in each group.A 0.25%adenine solution at 150mg·kg-1·d-1 was intragastrically administered daily for 8 consecutive weeks to establish a CKD rat model.The weight of renal tissue in each group was measured.The levels of creatinine(SCr),urea nitrogen(BUN),uric acid(UA),IL-6,IL-1β and TNF-α in the se-rum as well as 24-hour urinary total protein(24-hour UTP)of rats were determined by automatic biochemical analyzer.HE staining and Masson staining were used to detect the pathological damage and fibrosis degree in renal tissues,respectively.Western blot was used to detect the expression of LC3,Beclin1,p62 and PKG proteins in renal tissues.Commercial assay kits were used to detect the levels of NOS,nitric oxide(NO),cGMP protein in renal tissues.Results:Compared with the control group,the renal tissue weight,SCr,BUN,UA,24-h UTP,p62,IL-6,IL-1β,and TNF-α of the rats were increased in the model group(P<0.05),while LC3Ⅱ/Ⅰ ratio,Beclin1,NOS,NO,cGMP,PKG were decreased(P<0.05),and renal tis-sues showed significant pathological damage and fibrotic lesions.Compared with the model group,the renal tissue weight,SCr,BUN,UA,24h UTP,p62,IL-6,IL-1β,and TNF-α of the rats in the positive drug group and low-,medium-,and high-dose apigenin groups were decreased(P<0.05),while LC3Ⅱ/Ⅰ rati-o,Beclin1,NOS,NO,cGMP,PKG were increased(P<0.05),the pathological damage and fibrosis degree of renal tissues were alleviated.Moreover,the effects of apigenin was dose-dependent(P<0.05).Conclu-sions:Apigenin can alleviate pathological damage and fibrosis of renal tissues by promoting autophagy and in-hibiting inflammatory responses,thereby improving renal function in rats with chronic kidney disease.Its mechanism may be related to the activation of the NOS/cGMP/PKG signaling pathway.
赵笑晨;赵引;刘帅
河北省保定市第二中心医院,河北 保定 072750河北省雄县中医医院内三科,河北 雄县 071800河北省保定市第二中心医院,河北 保定 072750
慢性肾脏病芹菜素NOS/cGMP/PKG信号通路自噬
Chronic kidney diseaseApigeninNOS/cGMP/PKG signaling pathwayAutoph-agy
《河北医学》 2026 (7)
1123-1128,1191,7
河北省医学科学研究课题计划资助(20241637)
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