丹参素对糖尿病肾病大鼠MEK/ERK/Nrf2通路及肾脏纤维化的影响  

Effect of Danshensu on MEK/ERK/Nrf2 pathway and renal fibrosis in diabetic nephropathy rats

作　　者：吴平亚 冯磊[2] WU Ping-ya;FENG Lei(Zhangjiawan Street Community Health Service Center,Hongshan District,Wuhan,Hubei 430000;Tianyou Hospital Affiliated to Wuhan University of Science and Technology,Wuhan,Hubei 430064,China)

机构地区：[1]武汉市洪山区张家湾街社区卫生服务中心,湖北武汉430000 [2]武汉科技大学附属天佑医院,湖北武汉430064

出　　处：《热带医学杂志》2021年第10期1260-1264,F0004,共6页Journal of Tropical Medicine

基　　金：国家自然科学基金(81700446)。

摘　　要：目的探讨丹参素对糖尿病肾病(DN)大鼠肾组织中丝裂原细胞外信号调节激酶(MEK)/胞外信号调节激酶(ERK)/核因子E2相关因子2(Nrf2)通路及肾脏纤维化的影响。方法 50只SD大鼠用高糖高脂饲料喂养+尾静脉注射链脲佐菌素(35 mg/kg)建立DN模型,并随机分为模型组(DN组)、丹参素低剂量(5 mg/kg)组、丹参素中剂量(10 mg/kg)组、丹参素高剂量(20 mg/kg)组、阳性对照组(厄贝沙坦,25 mg/kg),每组10只;另取10只大鼠,经尾静脉注射生理盐水,作为正常对照组。各组均灌胃给予相应剂量药物,1次/d,共给药42 d。末次给药24 h后,酶联免疫吸附(ELISA)试剂盒检测大鼠空腹血糖含量及肾功能指标血清肌酐(Scr)、尿素氮(BUN)、尿液中24 h尿蛋白量;用苏木精-伊红(HE)及马森(Masson)染色观察大鼠肾组织病理变化及肾组织纤维化程度;蛋白免疫印迹法(Western blot)检测肾组织pMEK/MEK、p ERK/ERK、Nrf2蛋白表达及肾纤维化指标胶原蛋白I(Collagen I)表达。结果与正常对照组比较,DN组大鼠可见肾小管病变及肾间质纤维化等病理损伤严重,空腹血糖含量、肾功能指标及尿液中24 h尿蛋白含量、pMEK/MEK、pERK/ERK及CollagenⅠ蛋白表达均升高(P<0.05);Nrf2蛋白表达降低(P<0.05);丹参素可减轻大鼠肾小管病变及肾间质纤维化等病理损伤,降低DN大鼠空腹血糖、Scr、BUN及尿液中24 h尿蛋白含量、pMEK/MEK、p ERK/ERK及CollagenⅠ蛋白表达(P<0.05);促进Nrf2活化(P<0.05)。且丹参素剂量越高其对ND大鼠的治疗效果越显著,丹参素高剂量对DN大鼠的改善作用,与阳性对照组相比差异无统计学意义(P>0.05)。结论丹参素可抑制MEK、ERK蛋白磷酸化,上调Nrf2蛋白表达,可能通过抑制MEK/ERK/Nrf2通路改善DN模型大鼠肾功能损伤及肾脏纤维化。Objective To investigate the effects of Danshensu on mitogen extracellular signal-regulated kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear factor E2-related factor 2(Nrf2)signaling pathway and renal fibrosis in diabetic nephropathy(DN)rats. Methods SD rats were fed with high-sugar and high-fat feed+tail vein injection of streptozotocin(35 mg/kg)to establish a DN model,and were randomly divided into normal control group(control group),model group(DN group),and low Danshensu(5 mg/kg)dose group,middle Danshensu(10 mg/kg)dose group,high Danshensu(20 mg/kg)dose group,positive control group(irbesartan,25 mg/kg),10 rats in each group. Each group was given the corresponding dose of drugs by gavage,once a day,for a total of 42 days. 24 hours after the last administration,the ELISA kit was used to detect the fasting blood glucose content and renal function indexes of the rats,serum creatinine(Scr),blood urea nitrogen(BUN),and urine protein content in 24 hours;hematoxylin-eosin(HE)and Masson staining was used to observe the pathological changes of rat kidney tissue and the degree of renal tissue fibrosis;Western blot was used to detect the expression of pMEK/MEK,pERK/ERK,Nrf2 protein in renal tissue and the expression of collagen I(Collagen I),an index of renal fibrosis. Results Compared with the control group,rats in the DN group showed severe pathological damage such as renal tubular lesions and renal interstitial fibrosis,fasting blood glucose levels,renal function indicators,and 24 h urine protein content,pMEK/MEK,pERK/ERK and Collagen Ⅰ protein expression increased(P<0.05);Nrf2 protein expression decreased(P<0.05);Danshensu can alleviate pathological damage such as renal tubular lesions and renal interstitial fibrosis in rats,and reduce fasting blood glucose,Scr,24 h urine protein content in BUN and urine,pMEK/MEK,pERK/ERK and CollagenⅠ protein expression,promote Nrf2 activation(P<0.05),and the higher the dose of Danshensu,the more significant the therapeutic effect on DN rats. Danshensu compared wi

关 键 词：丹参素 糖尿病肾病 丝裂原细胞外信号调节激酶 胞外信号调节激酶 核因子E2相关因子2 

分 类 号：R587.1[医药卫生—内分泌]