中药固本通络方对IgA肾病小鼠氧化应激作用机制的实验研究  

Effects of Gubentongluo Formula on Oxidative Stress Reflected by Expressions of PPARαand L-FABP in Mice with IgA Nephropathy

作　　者：李雯雯[1,2] 黄迪[1] 沈沛成[1] 吴卿[1] 孙川[1] 王娴娴[1] 何立群[1] 

机构地区：[1]上海中医药大学附属曙光医院肾内科,上海200021 [2]上海中医药大学附属上海市中西医结合医院,上海200082

出　　处：《四川大学学报（医学版）》2017年第2期210-215,共6页Journal of Sichuan University(Medical Sciences)

基　　金：上海市科委自然基金项目(No.12ZR1432400);中医临床重点项目(No.14401972203);中医引导项目(No.15401930100);上海市卫生和计划生育委员会科研课题(No.201440488);上海市中医药三年行动计划(No.ZY3-JSFC-2-1029)资助

摘　　要：目的探讨固本通络方治疗IgA肾病的作用机制。方法 C57BL/6小鼠经诱导建立IgA肾病动物模型后,随机分为模型组(n=10)、对照组(n=10)及治疗组(n=10),另取10只正常小鼠作为正常组(n=10)。造模结束后,治疗组予固本通络方1.67mL/(g·d)灌胃治疗,对照组予非诺贝特30mg/(kg·d)灌胃治疗,正常组和模型组予等量生理盐水灌胃,每日1次,均连续12周。造模前、治疗开始时(第0周)和第12周末时,测定各组小鼠尿白蛋白;治疗第12周末处死小鼠后取肾组织,通过HE染色和免疫荧光染色观察各组肾组织病理学改变和系膜区IgA沉积,Western blot法测定肾组织过氧化物酶体增殖物激活受体α(peroxisome proliferstor activated receptorα,PPARα)、肝脏型脂肪酸结合蛋白(liver fatty acid-binding protein,L-FABP)、4-羟壬烯醛(4-hydroxy-2-nonenal,4-HNE)、血红素加氧酶1(hemeoxygenase-1,HO-1)的蛋白表达,实时荧光定量PCR检测肾组织PPARα、L-FABP mRNA表达。结果治疗第12周末,与正常组相比,模型组小鼠尿白蛋白增加,肾小球系膜区有病理损伤,肾组织PPARα、L-FABP的蛋白和mRNA表达降低,4-HNE和HO-1的蛋白表达增高,差异均有统计学意义(P<0.01)。与模型组相比,对照组和治疗组尿白蛋白降低,系膜区病理损伤减轻,肾组织PPARα、L-FABP的蛋白和mRNA表达增高,4-HNE和HO-1的蛋白表达降低,差异均有统计学意义(P<0.01);但与正常组相比,对照组和治疗组上述指标的差异均有统计学意义(P<0.01)。与对照组相比,治疗组上述指标的差异仍有统计学意义(P<0.05)。结论固本通络方能有效改善IgA肾病小鼠蛋白尿及肾小球系膜区病理损伤,可能与其调节PPARα、L-FABP的表达,进而改善氧化应激反应有关。Objective To determine the underlying mechanism of Gubentongluo Formula in the treatment of IgA nephropathy （IgAN）. Methods C57BL/6 mice were randomly divided into four groups： normal group （n =10）, IgAN group （n =10）, control group （n =10） and treatment group （n =10）. Mice in the normal and IgAN groups were intragastricly administered with normal saline for 12 weeks; while those in the control and treatment groups were given fenofibrate 〔30 mg/（kg·d） and Gubentongluo Formula 〔1.67 mL/（g·d）〕, respectively. Urinary albumin was detected at week 0 and 12. At week 12, protein expressions of peroxisome proliferstor activated receptor α （PPARα）, liver fatty acid-binding proteins （L-FABP）, 4-hydroxy-2-nonenal （4-HNE）, and hemeoxygenase-1（HO-1） in renal tissues were determined by Western blot; mRNA expressions of PPARα and L-FABP in renal tissues were determined by florescent quantitative reverse transcription-polymerase chain reaction （qRT-PCR）. Results At week 12, higher levels of urinary albumin, pathological injuries in glomerular mesangial area, and lower expressions of protein and mRNA of PPARα and L-FABP were found in mice in the IgAN group compared with those in the normal group （P 〈0.01）. The levels of those indicators decreased in those treated with fenofibrate and Gubentongluo Formule, but still higher than the normal controls （P 〈0.01）. The mice treated with Gubentongluo Formula had more significant improvement than those treated with fenofibrate （P 〈0.05）. Conclusion [CM（155.3mm]Gubentongluo formula can improve proteinuria and pathological injuries in glomerular mesangial area of IgAN mice, due to reduction of oxidative stress in renal tissues through regulating the expressions of PPARα and L-FABP.

关 键 词：IGA肾病 固本通络方 PPARΑ L-FABP 氧化应激 

分 类 号：R285.5[医药卫生—中药学]