氧化苦参碱通过调控肿瘤坏死因子样弱凋亡诱导因子蛋白表达影响慢性肾脏病大鼠继发性甲状旁腺功能亢进发展进程的机制  

Effect of oxytocin alkaloid regulating tumor necrosis factor-like weak inducer of apoptosis protein expression on the development of secondary hyperparathyroidism in rats with chronic kidney disease

作　　者：晏影 时潇诺 段文浩 郑守华[1] Yan Ying;Shi Xiaonuo;Duan Wenhao;Zheng Shouhua(Department of Thyroid Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院甲状腺外科,郑州450052

出　　处：《中华实验外科杂志》2023年第9期1737-1740,共4页Chinese Journal of Experimental Surgery

基　　金：河南省科技攻关项目(222102310553)。

摘　　要：目的探讨氧化苦参碱(Oxy)通过调控肿瘤坏死因子样弱凋亡诱导因子(TWEAK)蛋白表达对大鼠继发性甲状旁腺功能亢进症发展进程的影响作用及其作用机制。方法将20只6周龄雄性Sprague-Dawley(SD)大鼠根据随机数目表分配法随机分为5组,每组4只:正常对照组(Con)、造模对照组(VC)、低浓度氧化苦参碱干预组(VC+Oxy-L)、中浓度氧化苦参碱干预组(VC+Oxy-M)、高浓度氧化苦参碱干预组(VC+Oxy-H)。采用高腺嘌呤、高磷饮食制备大鼠慢性肾脏病模型。VC+Oxy组自造模第5周开始按照分组以25、50、100 mg/(kg·d)的剂量向大鼠腹腔注射4 ml的氧化苦参碱溶液,Con组及VC组给予同剂量生理盐水腹腔注射。检测造模8周后大鼠血清中肌酐(SCr)、尿素氮(BUN)、碱性磷酸酶(ALP)、钙、磷及甲状旁腺素(iPTH)的浓度。采用蛋白质印迹法(Western blot)、荧光定量聚合酶链式反应(PCR)检测大鼠肾脏肿瘤坏死因子样弱凋亡诱导因子(TWEAK)表达水平。两组间均数比较采用独立样本t检验,多组间均数比较采用单因素方差分析。结果VC组大鼠SCr、BUN、ALP、iPTH水平高于Con组[(190.25±88.96)μmol/L比(24.00±2.94)μmol/L、(18.60±12.01)mmol/L比(5.10±1.02)mmol/L、(199.00±23.62)mmol/L比(113.5±33.36)mmol/L、(56.70±4.64)ng/L比(8.65±0.94)ng/L,t=4.828、2.871、4.350、10.630,P<0.05]。各VC+Oxy组大鼠SCr、BUN、ALP、iPTH均较VC组明显下降,其中以VC+Oxy-M组大鼠SCr、ALP水平和VC+Oxy-L组iPTH水平较VC组降低最明显[(84.00±41.66)μmol/L比(190.25±88.96)μmol/L、(129.00±19.57)mmol/L比(199.00±23.62)mmol/L、(30.58±8.28)ng/L比(56.70±4.64)ng/L,t=3.806、3.562、5.783,P<0.05]。VC组大鼠肾脏中TWEAK基因及蛋白相对表达量高于Con组(3.76±1.61、1.17±0.14比1.01±0.19、0.49±0.02,t=4.457、6.857,P<0.05);VC+Oxy组大鼠TWEAK基因及蛋白相对表达量低于VC组,其中以VC+Oxy-H组较VC组降低最为明显(0.56±0.42、0.71±0.15比3.76±1.61、1.17±0.14,t=5.189、4.Objective To explore the effect of oxysophocarpine(Oxy)on the development of secondary hyperparathyroidism in rats by regulating the expression of tumor necrosis factor-like weak inducer of apoptosis(TWEAK)protein.Methods Totally,206-week-age male Sprague-Dawley(SD)rats were randomly divided into five groups(n=4 each):normal control group(Con),model control group(VC),low-dose Oxy intervention group(VC+Oxy-L),medium-dose Oxy intervention group(VC+Oxy-M),and high-dose Oxy intervention group(VC+Oxy-H).In the first 4 weeks,the rats were fed on a high adenine and high phosphorus diet to induce the VC model.At the 5th week,the VC+Oxy groups were injected intraperitoneally with 4 ml of Oxy solution at doses of 25,50,100 mg/(kg·d),respectively.The Con and VC groups were injected with the same dose of saline solution.After 8 weeks of modeling,the concentrations of serum creatinine(SCr),blood urea nitrogen(BUN),alkaline phosphatase(ALP),calcium,phosphorus,and intact parathyroid hormone(iPTH)were measured.The expression levels of TWEAK in the rat kidneys were detected using Western blotting and fluorescence quantitative polymerase chain reaction(PCR).Independent sample t-test was used for comparisons between two groups,and one-way analysis of variance(ANOVA)was used for comparisons among multiple groups.Results The levels of SCr,BUN,ALP,and iPTH in the VC group were higher than those in the Con group[(190.25±88.96)vs.(24.00±2.94)μmol/L,(18.60±12.01)vs.(5.10±1.02)mmol/L,(199.00±23.62)vs.(113.5±33.36)mmol/L,(56.70±4.64)vs.(8.65±0.94)ng/L,t=4.828,2.871,4.350,10.630,P<0.05].The levels of SCr,BUN,ALP,and iPTH in the VC+Oxy groups were significantly lower than those in the VC group,with the VC+Oxy-M group showing the most significant reductions in SCr and ALP levels,and the VC+Oxy-L group showing the most significant reduction in iPTH levels[(84.00±41.66)vs.(190.25±88.96)μmol/L,(129.00±19.57)vs.(199.00±23.62)mmol/L,(30.58±8.28)vs.(56.70±4.64)ng/L,t=3.806,3.562,5.783,P<0.05].The relative expression levels of the T

关 键 词：甲状旁腺功能亢进症 氧化苦参碱 肿瘤坏死因子样弱凋亡诱导因子蛋白 肿瘤坏死因子 

分 类 号：R285.5[医药卫生—中药学]