摘要
目的 分析穿山龙总皂苷对膜性肾病大鼠肾组织M型磷脂酶A2受体(Phospholipase A2 receptor, PLA2R)和免疫球蛋白G亚型4(Immunoglobulin G4,IgG4)表达影响及可能机制。方法 将40只SPF级雄性SD大鼠按随机数字表法分为对照组、模型组、贝那普利组(10 mg/kg)、低和高剂量穿山龙总皂苷组(80 mg/kg、160 mg/kg),每组各8只。除对照组,其余4组采用Border法制备膜性肾病模型,造模成功后,贝那普利组灌胃给予贝那普利10 mg/(kg·d),低和高剂量穿山龙总皂苷组分别灌胃给予穿山龙总皂苷80 mg/(kg·d)、160 mg/(kg·d),对照组、模型组灌胃给予10 ml/(kg·d)生理盐水。连续给药4周后,检测24 h尿蛋白、白蛋白、血肌酐、血尿素氮、尿酸水平,HE染色观察肾脏病理改变,蛋白免疫印迹法检测肾脏中M型PLA2R、IgG4、磷酸化磷脂酰肌醇3-激酶(Phosphorylated phosphoinositide 3-kinase, p-PI3K)、磷酸化蛋白激酶B(Phosphorylated protein kinase B,p-AKT)、核因子E2相关因子2(Nuclear factor E2-related factor 2,Nrf2)、血红素加氧酶(Heme oxygenase-1,HO-1)表达水平。结果 与模型组比较,贝那普利组、高剂量穿山龙总皂苷组白蛋白水平明显升高,血肌酐、血尿素氮、尿酸水平明显降低,差异均有统计学意义(P>0.05)。与模型组比较,贝那普利组、低剂量和高剂量穿山龙总皂苷组肾脏病理改变明显改善,24 h尿蛋白水平及肾脏中M型PLA2R、IgG4、p-PI3K、p-AKT表达水平明显降低,肾脏中Nrf2、HO-1表达水平明显增加,差异均有统计学意义(P<0.05)。结论 穿山龙总皂苷对膜性肾病大鼠的肾脏具有保护作用,其机制可能与降低PLA2R、IgG4表达,抑制PI3K/AKT通路,激活Nrf2/HO-1通路相关。
Objective To investigate the effect of total saponins from Dioscoreae Nipponicae Rhizoma on the expression of M-type phospholipase A2 receptor(PLA2R)and immunoglobulin G4(IgG4)in the renal tissue of rats with membranous nephropathy(MN),as well as to explore the potential underlying mechanisms.Methods Forty male SPF SD rats were divided into five groups by random number table:control,model,benazepril(10 mg/kg),and low-and high-dose saponin groups(total saponins from Dioscoreae Nipponicae Rhizoma,80 mg/kg and 160 mg/kg,respectively),with eight in each group.All groups except the control group were induced with MN using the Border method.After successful modeling,the benazepril group received 10 mg/(kg·d)benazepril by gavage,while the saponin groups received their respective doses of total saponins(80 mg/kg and 160 mg/kg)by gavage.The control and model groups were given 10 mL/(kg·d)of normal saline.After four weeks of treatment,24-hour urinary protein,albumin,serum creatinine,blood urea nitrogen,and uric acid were assessed.Renal pathology was observed via HE staining.The expressions of M-type PLA2R,IgG4,phosphorylated phosphoinositide 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),nuclear factor E(2)-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in renal tissues were detected by Western blot.Results Compared with the model group,the benazepril and high-dose saponin groups showed significant increases in albumin and decreases in serum creatinine,blood urea nitrogen,and uric acid(P<0.05).Renal pathology was notably improved,and the expressions of M-type PLA2R,IgG4,p-PI3K,and p-AKT in the kidneys were reduced,while the expressions of Nrf2 and HO-1 were elevated in both benazepril and saponin groups(P<0.05).Conclusion Total saponins from Dioscoreae Nipponicae Rhizoma exert protective effects on the kidneys of MN rats.The potential mechanisms may involve down-regulating PLA2R and IgG4,inhibiting the PI3K/AKT pathway,and activating the Nrf2/HO-1 pathway.
作者
杨薇
平高华
张峥
姚吉太
刘光珍
YANG Wei;PING Gao-hua;ZHANG Zheng;YAO Ji-tai;LIU Guang-zhen(Department of NephrologyⅢ,Shanxi Academy of Traditional Chinese Medicine,Taiyuan Shanxi 030000)
出处
《世界中西医结合杂志》
2024年第2期274-280,共7页
World Journal of Integrated Traditional and Western Medicine
基金
山西省中医药管理局科研课题计划(2022ZYYC004)。
