自拟中药汤剂联合百令胶囊对慢性肾脏病大鼠肾脏炎症及p38 MAPK信号通路的影响  

Effect of Chinese Herbal Decoction Combined with Bering Capsule on Renal Inflammation and p38 MAPK Signal Pathway in Rats with Chronic Kidney Disease

作　　者：郭亚平 郭补林 赵亚峰 刘旭琴 鲁小庆 赵东艳 闫隐隐 GUO Yaping;GUO Bulin;ZHAO Yafeng;LIU Xuqin;LU Xiaoqing;ZHAO Dongyan;YAN Yinyin(Yulin Hospital of Traditional Chinese Medicine,Yulin 719000,Shaanxi,China;Shanxi Provincial Hospital of Traditional Chinese Medicine,Xian 710003,Shaanxi,China)

机构地区：[1]榆林市中医医院,陕西榆林719000 [2]陕西省中医医院,陕西西安710003

出　　处：《贵州医科大学学报》2020年第4期444-450,共7页Journal of Guizhou Medical University

基　　金：陕西省中医药管理局中医药科学技术研究课题(LCPT007);榆林市科技项目(2060499-06)。

摘　　要：目的:观察中药汤剂联合百令胶囊对慢性肾脏病(CKD)大鼠的治疗作用及对p38丝裂原活化蛋白激酶(p38 MAPK)信号通路的影响。方法:40只雄性SD大鼠随机分为空白组、CKD组、百令胶囊和中药汤剂联合百令胶囊组,后3组大鼠采用灌胃腺嘌呤方法建立CKD模型;模型建立后,百令胶囊组和中药汤剂联合百令胶囊组分别用相应药物灌胃干预,空白组和CKD组给予等量生理盐水,连续给药4周;给药结束后处死大鼠,测定各组大鼠血清中血肌酐(Scr)、尿素氮(BUN)及24 h尿白蛋白(UAlb/24h)和尿N-乙酰-β-D-氨基葡萄糖苷(NAG)酶含量,ELISA检测各组大鼠肾脏组织中Ⅰ型胶原(Col-Ⅰ)和Ⅲ型胶原(Col-Ⅲ)含量,HE染色观察肾组织形态学,qRT-PCR检测炎症因子白细胞介素-6(IL-6)、IL-8和干扰素-γ(INF-γ)mRNA表达,Western blot检测p38 MAPK、p-p38 MAPK、JNK、p-JNK、ERK1/2和p-ERK1/2蛋白表达。结果:与空白组比较,CKD组Scr、BUN、UAlb/24h、尿NAG酶、Col-Ⅰ和Col-Ⅲ明显升高(P<0.01),肾组织出现明显病理变化,IL-6、IL-8、INF-γmRNA水平明显增加(P<0.01),肾组织中p38 MAPK、JNK、p-JNK、ERK1/2和p-ERK1/2蛋白表达显著升高(P<0.01);与CKD组比较,百令胶囊组和中药汤剂联合百令胶囊组上述肾功能损伤指标和炎症因子均降低(P<0.05),肾组织病理学变化被改善,肾组织中p38 MAPK、JNK、p-JNK、ERK1/2和p-ERK1/2蛋白表达降低(P<0.05或P<0.01);与百令胶囊组比较,中药汤剂联合百令胶囊组上述肾功能损伤指标和炎症因子的下降更明显,p-JNK蛋白表达降低(P<0.05)。结论:中药汤剂联合百令胶囊可降低腺嘌呤诱导的大鼠肾功能损害和炎症反应,其机制可能与抑制p38 MAPK信号通路某些蛋白质的过度激活有关。Objective:To observe the therapeutic effect of traditional Chinese medicine decoction combined with Bailing capsule on chronic kidney disease(CKD)rats and its effect on p38 MAPK signaling pathway.Methods:The 40 male SD rats were randomly divided into blank group,CKD group,Bering capsule and traditional Chinese medicine decoction combined with Bailing capsule group,and the CKD model was established by gavage adenine method in the latter three groups.After the model was established,Bailing capsule group and traditional Chinese medicine decoction combined with Bailing capsule group were given the same amount of normal saline in the blank group and the CKD group,respectively,for 4 weeks.The serum contents of serum creatinine(Scr),urea nitrogen(BUN),24 h urinary albumin(UAlb/24 h)and enzyme content of urinary N-acetylβ-D-glucosamine(NAG)were determined in each group.The contents of I collagen(Col-Ⅰ)andⅢcollagen(Col-Ⅲ)in kidney tissue of each group were detected by ELISA test,and the renal histomorphology was observed by HE staining.The inflammatory factors interleukin-6(IL-6),IL-8,interferon-γ(INF-γ)mRNA and the protein expression of p38 MAPK,p-p38 MAPK,JNK,p-JNK,ERK1/2 and p-ERK1/2 were detected by Western blot and qRT-PCR.Results:Scr,BUN,UAlb/24 h,Urine NAG enzyme,Col-Ⅰand Col-Ⅲincreased significantly in CKD group compared with blank group(P<0.01).Renal tissue showed obvious pathological changes and the level of IL-6,IL-8 and INF-γmRNA increased significantly(P<0.01).The protein expression of p38MAPK,JNK,p-JNK,ERK1/2 and p-ERK1/2 in renal tissues increased significantly(P<0.01).Compared with CKD group,the above indexes of kidney function injury and inflammatory factors were significantly decreased in Bailing capsule group and traditional Chinese medicine decoction combined with Bailing capsule group(P<0.05).Renal histopathological changes were improved and the protein expression of p38 MAPK,JNK,p-JNK,ERK1/2 and p-ERK1/2 in renal tissues was significantly decreased(P<0.05 or P<0.01).Compared with Bailin

关 键 词：大鼠 Sprague-Dawley 炎症 慢性肾脏病 P38MAPK信号通路 肾功能 百令胶囊 

分 类 号：R285.5[医药卫生—中药学]