贝前列素钠联合前列地尔治疗老年早期糖尿病肾病患者的临床研究  

Clinical trial of beraprost sodium combined with alprostadil in the treatment of elderly patients with early diabetic nephropathy

作　　者：崔利娜[1] 付艳芹[1] 辛雅萍[1] 姜得悦 CUI Li-na;FU Yan-qin;XIN Ya-ping;JIANG De-yue(Department of Endocrinology,The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,Henan Province,China)

机构地区：[1]郑州大学第二附属医院内分泌科,河南郑州450014

出　　处：《中国临床药理学杂志》2020年第22期3616-3620,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察贝前列素钠联合前列地尔对老年早期糖尿病肾病(DN)患者NOD样受体蛋白3(NLRP3)炎症小体表达的影响。方法将老年DN患者142例按随机数字表法分为试验组71例及对照组71例。2组均接受降糖、优质低蛋白饮食和对症治疗。对照组给予前列地尔,每天10μg,静脉滴注,试验组前2周给予前列地尔,后2周给予贝前列素钠,每次40μg,每天3次,口服。2组均治疗4周。治疗前后,比较2组肾功能指标、氧化应激指标、NLRP3、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶-1(Caspase-1)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18),并记录2组治疗期间药物不良反应发生情况。结果治疗后,试验组和对照组NLRP3 mRNA分别为18.01±0.91,22.37±1.06,ASC mRNA分别为19.98±0.85,23.59±1.02,Caspase-1 mRNA分别为20.42±0.95,23.91±1.04,NLRP3蛋白分别为0.28±0.03,0.39±0.06,ASC蛋白分别为0.32±0.04,0.48±0.07,Caspase-1蛋白分别为0.30±0.05,0.41±0.08,差异均有统计学意义(均P<0.01)。试验组和对照组的IL-18分别为(16.50±1.97)和(21.71±2.45)pg·mL^-1,IL-1β分别为(7.59±2.33),和(12.37±3.24)pg·mL^-1,超氧化物歧化酶(SOD)分别为(55.48±9.78),(46.20±7.36)U·mg-1,谷胱甘肽过氧化物酶(GSH-Px)分别为(169.29±18.40),(140.59±13.62)kU·L-1,丙二醛(MDA)分别为(6.90±1.40),(9.96±2.28)mmol·mg-1,尿蛋白排泄率(UAER)分别为(64.40±7.40),(91.59±9.48)mmol·L-1,血肌酸酐(Scr)分别为(91.90±8.09),(120.47±10.60)μmol·L-1,尿足细胞标志蛋白(PCX)分别为(1.47±0.28),(2.62±0.39)mg·mL^-1,亮氨酸氨基肽酶(LAP)分别为(8.41±1.69),(11.61±2.48)mg·mL^-1,差异均有统计学意义(均P<0.05)。试验组和对照组的药物不良反应发生率分别为4.63%(4例/71例),11.27%(8例/71例),差异无统计学意义(P>0.05)。结论贝前列素钠联合前列地尔能够有效降低老年DN患者降低尿蛋白,改善肾功能,疗效显著,其机制与改善机体氧化应激状态、抑制NALP3炎症信号通路的活化及�Objective To observe the effect of beraprost sodium combined with alprostadil on the expression of NOD-like receptor protein 3(NLRP3) inflammasome in elderly patients with early diabetic nephropathy(DN). Methods A total of 142 elderly patients with DN were divided into treatment group(71 cases) and control group(71 cases) according to the random number table method. Both groups were received hypoglycemic,high-quality low-protein diet and symptomatic treatment. On this basis,control group was treated with alprostadil,10 μg,qd,intravenously injected,treatment group was treated with alprostadil in the first two weeks,and givenberaprost sodium 40 μg,tid,oral on the last two weeks. The treatment time of both groups was 4 weeks. Before and after treatment,the renal function indicators,oxidative stress indicators,NLRP3,apoptosis-related dot-like protein(ASC),Caspase-1,interleukin-1β(IL-1β),interleukin-18(IL-18),and the adverse drug reactions of the two groups during treatment were compared. Results After treatment,NLRP3 mRNA in treatment group and control group were 18. 01 ± 0. 91,22. 37 ± 1. 06,ASC mRNA were19. 98 ± 0. 85,23. 59 ± 1. 02,Caspase-1 mRNA were 20. 42 ± 0. 95,23. 91 ± 1. 04, NLRP3 protein were0. 28 ± 0. 03,0. 39 ± 0. 06,ASC protein were 0. 32 ± 0. 04,0. 48 ± 0. 07,Caspase-1 protein were 0. 30 ± 0. 05,0. 41 ± 0. 08,all with significant difference(all P < 0. 01). The IL-18 in treatment group and control group were(16. 50 ± 1. 97),(21. 71 ± 2. 45) pg·mL^-1,IL-1β were(7. 59 ± 2. 33),(12. 37 ± 3. 24) pg·mL^-1,superoxide dismutase(SOD) were(55. 48 ± 9. 78),(46. 20 ± 7. 36) U·mg-1,glutathione peroxidase(GSH-Px) were(169. 29 ± 18. 40),(140. 59 ± 13. 62) k U·L-1,malondialdehyde(MDA) were(6. 90 ± 1. 40),(9. 96 ± 2. 28)mmol·mg-1,urine protein excretion rate(UAER) were(64. 40 ± 7. 40),(91. 59 ± 9. 48) mmol·L-1,serum creatinine(Scr) were(91. 90 ± 8. 09),(120. 47 ± 10. 60) μmol·L-1,podocalyxin(PCX) were(1. 47 ± 0. 28),(2. 62 ± 0. 39) mg·mL^-1,leucine aminopeptidase(LAP) were(8. 4

关 键 词：老年患者 早期糖尿病肾病 贝前列素钠 前列地尔 NOD样受体蛋白3炎症小体 

分 类 号：R97[医药卫生—药品]