基于ERK/NF⁃κB通路探讨益肾散结化瘀复方对IgA肾病大鼠肾内小动脉病变的防治作用  

Protective effects of Yishen Sanjie Huayu compound on the renal artery disease in rats with IgA nephropathy through ERK/NF⁃κB pathway

作　　者：刘璐 张晓东 田耘 LIU Lu;ZHANG Xiao-dong;TIAN Yun(The First Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of Nephrology,the Third Hospital of Baoji,Baoji 721000,China;Department of Nephropathy,Shaanxi Hospital of Traditional Chinese Medicine,Xi'an 710003,China)

机构地区：[1]陕西中医药大学第一临床医学院,陕西咸阳712046 [2]宝鸡市第三医院肾内科,陕西宝鸡721000 [3]陕西省中医医院肾病一科,陕西西安710003

出　　处：《海南医学院学报》2021年第24期1865-1871,1877,共8页Journal of Hainan Medical University

基　　金：国家自然科学基金资助项目(81774123);陕西省重点研发计划项目(2018ZDXM-SF-011)。

摘　　要：目的:观察益肾散结化瘀复方对IgA肾病(IgAN)大鼠ERK/NF⁃κB信号通路的影响,并探讨其防治IgA肾病肾内小动脉病变的作用。方法:将55只雄性SD大鼠随机分为空白组、模型组、肾复康Ⅱ号胶囊组和氯沙坦钾片组,采用牛血清白蛋白灌胃,四氯化碳皮下注射以及脂多糖尾静脉注射方法建立IgAN大鼠模型,肾复康Ⅱ号胶囊组及氯沙坦钾片组每天分别给予药物混悬液2 mL/只于造模1周后开始灌胃治疗,空白组及模型组以等体积生理盐水灌胃,于给药后4、8、12周检测大鼠24 h尿蛋白(UTP),12 w后检测大鼠血肌酐(SCr)、尿素氮(BUN)、醛固酮(ADS)、血管紧张素Ⅱ(AngⅡ),免疫组织化学Envi⁃sion System二步法检测大鼠肾脏总体及小动脉区域血管内皮生长因子(VEGF)、人基质金属蛋白酶⁃9(MMP⁃9)、增殖细胞核抗原(PCNA)、细胞外调节蛋白激酶(ERK)1/2、核转录因子⁃κB(NF⁃κB)的表达,同时检测大鼠肾组织小动脉的内膜、中膜、管壁/血管外径值。结果:与模型组比较,肾复康Ⅱ号胶囊组及氯沙坦钾片组肾组织中VEGF、MMP⁃9、PCNA、ERK1/2、NF⁃κB表达降低(P<0.05),24 h UTP及SCr、BUN水平降低(P<0.05),肾组织损伤情况均有所减轻;内膜及管壁/血管外径值明显减小(P<0.01),各组间ADS相比无明显差异,氯沙坦钾片组AngⅡ较模型组降低(P<0.05)。结论:益肾散结化瘀复方可通过抑制IgA肾病大鼠ERK/NF⁃κB信号通路,降低VEGF、MMP⁃9、PCNA、ERK1/2、NF⁃κB水平,抑制肾内小动脉血管内皮细胞增殖,减轻肾脏损伤。Objective:To observe the effect of Yishen Sanjie Huayu compound on the ERK/NFκB signaling pathway in IgA nephropathy(IgAN)rats,and to explore its effects on intrarenal arteriole disease in IgAN rats.Methods:Fiftyfive male SD rats were randomly divided into the blank group,the model group,the ShenfukangⅡcapsule group and the Losartan potassium tablet group.IgAN rat models were induced by intragastric administration of bovine serum albumin(BSA)and carbon tetrachloride(CCl4)subcutaneous injection of lipopolysaccharide(LPS)through tail vein.The ShenfukangⅡcapsule group and the Losartan potassium tablet group were given in suspension at the concentration of 2 mL/d for one week after modeling establishment was started.While the blank group and the model group were given an equal volume of normal saline.The 24 h urine protein(UTP)of the rats was measured at 4,8,and 12 weeks after the treatment;the blood creatinine(SCr),urea nitrogen(BUN),aldosterone(ADS),angiotensinⅡ(AngⅡ)were measured after 12 weeks.Immunohistochemical Envision System twostep method was used to detect the expressin level of vascular endothelial growth factor(VEGF)and metalloproteinase9(MMP9),proliferating cell nuclear antigen(PCNA),extracellular regulatory protein kinase(ERK)1/2,nuclear transcription factorκB(NFκB),and the small arteries of rat kidney tissue,the intima,media,vessel wall/vascular outer diameter values were detected too.Results:Compared with the model group,the expressions of VEGF,MMP9,PCNA,ERK1/2 and NFκB in kidney tissues of the ShenfukangⅡcapsule group and the Losartan potassium tablet group were significantly decreased(P<0.05),24 h UTP,SCr,BUN levels were decreased too(P<0.05),and the damages in kidney tissues were alleviated;intima and vessel wall/vascular outer diameter values were significantly reduced(P<0.01).There was no significant difference in ADS between those groups,but the AngⅡlevels of the Tanpotassium tablets group was significanty lower than that of the model group(P<0.05).Conclusion:Yishen Sanjie Huayu

关 键 词：IGA肾病 益肾散结化瘀复方 ERK/NF⁃κB信号通路 动物实验 中医药疗法 

分 类 号：R285.5[医药卫生—中药学]