摘要
目的:探讨甲基莲心碱(Nef)调节MAPK/NF-κB通路对肾病综合征(NS)大鼠炎症损伤的影响.方法:将SD大鼠分为空白对照组(CK组)、Model组、低剂量Nef组(Nef-L组,2.5 mg/kg)、高剂量Nef组(Nef-H组,5 mg/kg)、醋酸泼尼松组(PA组,6.3 mg/kg)、Anisomycin(MAPK激动剂)组(5 μmol/L)、Nef-H+Anisomycin组(5 mg/kg+5 μmol/L),每组12只.除CK组外,其他组均通过尾静脉注射阿霉素以诱导NS大鼠模型,CK组大鼠在相同时间内通过尾静脉注射等体积的生理盐水.建模成功后,进行给药处理,1次/d,持续4周.检测24 h尿蛋白含量、血清中肌酐(Scr)、白蛋白(ALB)、尿素氮(BUN)水平、肾组织病理及肾组织TNF-α、IL-6、IL-1β水平;TUNEL染色检测大鼠肾组织中细胞凋亡情况;Western blot检测大鼠肾组织中p-p38、p-JNK、p-ERK1/2、p-NF-κB p65蛋白表达.结果:与CK组比较,Model组大鼠肾组织病理损伤严重,24 h尿蛋白、Scr、BUN、TNF-α、IL-6、IL-1β、细胞凋亡率、p-p38、p-JNK、p-ERK1/2、p-NF-κB P65蛋白上调,ALB水平下调(P<0.05);与Model组相比,Nef-L组、Nef-H组、PA组肾组织病理损伤严重,24 h尿蛋白、Scr、BUN、TNF-α、IL-6、IL-1β、细胞凋亡率、p-p38、p-JNK、p-ERK1/2、p-NF-κB p65蛋白表达降低,ALB水平升高,Anisomycin组大鼠肾组织病理损伤加剧,24 h尿蛋白、Scr、BUN、TNF-α、IL-6、IL-1β、细胞凋亡率、p-p38、p-JNK、p-ERK1/2、p-NF-κB p65蛋白表达升高,ALB水平降低(P<0.05);Anisomycin减弱了高剂量 Nef 对NS大鼠的影响.结论:Nef可能通过抑制MAPK/NF-κB通路减轻NS大鼠炎症损伤.
Abstract
Objective:To investigate the influences of Neferine(Nef)on inflammatory injury in nephrotic syndrome(NS)rats by regulating the MAPK/NF-κB pathway.Methods:SD rats were separated into control check group(CK group),Model group,low-dose Nef group(Nef-L group,2.5 mg/kg),high-dose Nef group(Nef-H group,5 mg/kg),prednisone acetate group(PA group,6.3 mg/kg),Anisomycin(MAPK agonist)group(5 μmol/L),Nef-H+Anisomycin group(5 mg/kg+5 μmol/L),with 12 rats in each group.Except for the CK group,all other groups were injected with doxorubicin through the tail vein to induce the NS rat model.Rats in CK group were injected with an equal volume of normal saline through the tail vein at the same time.After successful modeling,dosing treatment was performed once a day for 4 weeks.Detected 24-hour urine protein content,serum creatinine(Scr),albumin(ALB),urea nitro-gen(BUN)levels,renal tissue pathology,and levels of TNF-α,IL-6,and IL-1β in renal tissue;TUNEL staining was performed to detect cell apoptosis in rat kidney tissue;Western blot was performed to detect the expression of p-p38,p-JNK,p-ERK1/2 and p-NF-κB p65 proteins in rat kidney tissue.Results:Compared with CK group,Model group had severe renal tissue pathological damage,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB p65 protein expressions were increased,while ALB level was decreased(P<0.05);compared with Model group,the renal tissue pathological damage of rats in Nef-L group,Nef-H group and PA group were severe,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB P65 protein expressions were decreased,while ALB level was increased,the renal tissue pathological damage in the Anisomycin group was aggravated,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB p65 protein expressions were increased,while ALB level was decreased(P<0.05);Anisomycin attenu-ated the effects of high doses of Nef on NS rats.Conclusion:Nef may alleviate the inflammatory injury in NS rats by inhibiting MAPK/NF-κB signaling pathway.
国家科技期刊平台
NSTL
万方数据