[1]阮诺冰,李金菊,林逸轩,等.苁归益肾胶囊对糖尿病肾病大鼠肾纤维化及MEK/ERK信号通路的影响[J].陕西中医,2023,(2):139-143,148.[doi:DOI:10.3969/j.issn.1000-7369.2023.02.001]
　RUAN Nuobing,LI Jinju,LIN Yixuan,et al.The effect of Conggui Yishen capsules on renal fibrosis and MEK/ERK signaling pathway in rats with diabetic kidney disease[J].,2023,(2):139-143,148.[doi:DOI:10.3969/j.issn.1000-7369.2023.02.001]
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苁归益肾胶囊对糖尿病肾病大鼠肾纤维化及MEK/ERK信号通路的影响
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2023年2期
页码:
139-143,148
栏目:
基础研究
出版日期:
2023-02-05

文章信息/Info

Title:
The effect of Conggui Yishen capsules on renal fibrosis and MEK/ERK signaling pathway in rats with diabetic kidney disease
作者:
阮诺冰1; 李金菊2; 林逸轩3; 4; 王帆竞3; 4; 方朝晖3; 4
(1.安徽中医药大学研究生院,安徽 合肥 230038; 2.合肥市第一人民医院,安徽 合肥 230061; 3.安徽省中医药科学院中医药防治糖尿病研究所,安徽 合肥 230031; 4.安徽中医药大学第一附属医院,安徽 合肥 230031)
Author(s):
RUAN Nuobing; LI Jinju; LIN Yixuan; WANG Fanjing; FANG Zhaohui
(Graduate School of Anhui University of Traditional Chinese Medicine,Hefei 230038,China)
关键词:
糖尿病肾病;  苁归益肾胶囊;  肾脏纤维化;  丝裂原细胞外信号调节激酶/细胞外信号调节激酶信号通路;  组织转化生长因子β1
Keywords:
Diabetes kidney disease;  Conggui Yishen capsules;  Renal fibrosis;  MEK/ERK signaling pathway;  Transforming growth factor β1
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7369.2023.02.001
文献标志码:
A
摘要:
目的:探讨苁归益肾胶囊对糖尿病肾病(DKD)大鼠肾脏纤维化及丝裂原细胞外信号调节激酶/细胞外信号调节激酶(MEK/ERK)信号通路的影响。方法:高脂饲料联合小剂量链尿佐菌素(STZ)诱导DKD大鼠模型,造模成功后随机分为模型组、厄贝沙坦组及苁归益肾胶囊高、中、低剂量组,分别予0.9%氯化钠溶液5 ml/kg、厄贝沙坦15 mg/kg及苁归益肾胶囊1080、540、270 mg/kg灌胃,空白组大鼠予0.9%氯化钠溶液5 ml/kg灌胃,连续灌胃12周后收集标本。检测大鼠空腹血糖(FPG)、尿素氮(BUN)、肌酐(Scr)、24 h尿蛋白定量(24 hUP)水平,HE及Masson染色观察肾脏组织形态改变,Western blot检测肾脏组织转化生长因子β1(TGF-β1)、MEK、磷酸化丝裂原细胞外信号调节激酶(p-MEK)、ERK、磷酸化细胞外信号调节激酶(p-ERK)蛋白水平。结果:药物干预12周后,模型组、厄贝沙坦组、苁归益肾胶囊各剂量组FPG、BUN、Scr和24 hUP均比空白组高(P<0.05); 相较于模型组,苁归益肾胶囊高、中剂量组FPG降低(P<0.05),厄贝沙坦组、苁归益肾胶囊各剂量组BUN、Scr、24 hUP降低(P<0.05); HE染色结果显示,相较空白组,各造模组大鼠肾脏组织均有病理改变,各药物干预组肾脏病理改变与模型组相比有不同程度的改善。Masson染色显示模型组与各药物干预组肾脏胶原纤维增生情况较空白组严重,经药物干预的各组肾脏组织纤维化程度比模型组轻。模型组及各药物干预组TGF-β1表达量,MEK、ERK磷酸化水平较空白组明显升高(P<0.05),厄贝沙坦组及苁归益肾胶囊高、中剂量组TGF-β1表达量,MEK、ERK磷酸化水平比模型组低(P<0.05)。结论:苁归益肾胶囊能够缓解肾脏纤维化程度,可能是通过抑制TGF-β1介导的MEK/ERK信号通路活化发挥作用。
Abstract:
Objective:To investigate the effects of Conggui Yishen capsules on enal fibrosis and mitogenic extracellular signal-regulated kinase/extracellular signal-regulated kinase(MEK/ERK)signaling pathway in rats with diabetic kidney disease(DKD).Methods:The high-fat diet combined with low-dose streptozotocin(STZ)induced DKD rat model.After successful modeling,the rats were randomly divided into model group,Irbesartan group,and Conggui Yishen capsules high,medium and low dose groups,and were given saline 5 ml/kg,Irbesartan 15 mg/kg,Conggui Yishen capsules 1080,540,270 mg/kg by gavage,and blank group rats were given saline 5 ml/kg,and the specimens were collected after 12 consecutive weeks.Fasting blood glucose(FPG),urea nitrogen(BUN),creatinine(Scr)and 24 h urine protein quantification(24 hUP)levels were measured.The morphological changes of kidney tissues were observed by HE and Masson staining,and the levels of transforming growth factor β1(TGF-β1),MEK,phosphorylated mitogenic extracellular signal-regulated kinase(p-MEK),ERK,and phosphorylated extracellular signal-regulated kinase(p-ERK)proteins in kidney tissues were detected by Western blot.Results:After 12 weeks of drug intervention,FPG,BUN,Scr and 24 hUP were higher in the model group,the Irbesartan group and the Conggui Yishen capsules at all doses than in the blank group(P<0.05); compared with the model group,FPG was lower in the Conggui Yishen capsules high and medium dose groups(P<0.05).BUN,Scr and 24 hUP were lower in the Irbesartan group and the Conggui Yishen capsules at all doses(P<0.05).The results of HE staining showed that compared with the blank group,the kidney tissues of each modeling group had pathological changes,and the kidney pathological changes of each drug intervention group had different degrees of improvement compared with the modeling group.Masson staining showed that the kidney collagen fiber proliferation was more severe in the model group and each drug intervention group than in the blank group,and the kidney tissue fibrosis was less severe in each group with drug intervention than in the model group.The TGF-β1 expression,MEK and ERK phosphorylation levels were significantly higher in the model group and each drug intervention group compared with the blank group(P<0.05),and the TGF-β1 expression,MEK and ERK phosphorylation levels were lower in the Irbesartan group and the high and medium dose groups of Conggui Yishen capsules compared with the model group(P<0.05).Conclusion:The ability of Conggui Yishen capsules to alleviate the extent of renal fibrosis may act through inhibition of TGF-β1 mediated activation of the MEK/ERK signaling pathway.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(82174153,81573944, 81774286); 国家重点研发计划“战略性国际科技创新合作”重点专项(2020YFE0201800); 国家重点研发计划“中医药现代化研究”重点专项(2018YFC1704202); 国家中医临床研究基地业务建设第二批科研专项(JDZX2015123); 国家中医药管理局中医药重点学科(20091221); 第五批安徽省“特支计划”人才项目(20190028); 安徽省中医药领军人才及培养对象项目(20190027); 安徽省高校协同创新项目(GXXT-2020-025)
更新日期/Last Update: 2023-02-08