青蒿琥酯对糖尿病大鼠肾脏的保护作用及机制  

Protective effect and mechanism of artesunate on kidneys in diabetic rats

作　　者：梁晨 李维 陈怡 农晓琳[1] LIANG Chen;LI Wei;CHEN Yi;NONG Xiaoling(The Affiliated Stomatological Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学附属口腔医院,南宁530021

出　　处：《山东医药》2020年第14期9-12,共4页Shandong Medical Journal

摘　　要：目的观察青蒿琥酯(ART)对糖尿病大鼠肾脏的保护作用,并探讨其对肾组织自噬及纤维化的影响。方法将40只雄性SD大鼠随机分为正常对照组10只和模型组30只,模型组腹腔注射链脲佐菌素制作糖尿病模型,造模成功后,将模型组分为ART低剂量组、ART高剂量组、模型对照组各10只。ART低、高剂量组分别给予ART 50、100 mg/kg灌胃,正常对照组和模型对照组分别给予等量0.9%氯化钠溶液灌胃,均1次/d,连续3周。3周后收集收集24 h尿液检测尿素氮(SCr),采集动脉血检测血肌酐(SUN);处死大鼠,剖腹取双侧肾脏称重,计算肾脏指数(KI);行HE染色和PAS染色观察肾脏病理改变,Masson染色观察肾组织纤维化改变,免疫组化染色法检测肾组织纤维化相关蛋白TGF-β1、Smad2及自噬相关蛋白AMPK、LC3Ⅱ蛋白表达。结果与正常对照组相比,模型对照组SCr、SUN、KI升高(P均<0.05);肾脏病理改变明显,可见肾小球代偿性肥大,系膜基质增生,肾间质纤维化;肾组织TGF-β1、Samd2蛋白表达增高,AMPK、LC3Ⅱ蛋白表达降低(P均<0.05)。与模型对照组比较,ART低、高剂量组SCr、SUN、KI降低,肾小球、肾间质病变减轻,纤维化程度减轻。与ART高剂量组比较,ART低剂量组肾脏病理改善更为明显,肾组织TGF-β1、Samd2蛋白表达降低,AMPK、LC3Ⅱ蛋白表达升高(P均<0.05)。结论ART对糖尿病大鼠具有肾脏保护作用,该作用与其增强自噬从而抑制肾纤维化相关通路TGF-β1/Smad2活性有关。Objective To observe the protective effect of artesunate(ART)on the kidneys of diabetic rats and to explore its effect on renal autophagy and fibrosis.Methods Forty male SD rats were randomly divided into the normal control group(n=10)and model group(n=30).The rats in the model group were intraperitoneally injected with streptozotocin to make the diabetic models.After successful modeling,the model group was divided into the low-dose ART group,high-dose ART group and model control group,with 10 in each.The rats in the low-dose ART group and high-dose ART group were given 50 and 100 mg/kg ART by gavage;0.9%sodium chloride solution was given to the normal control group and model control group,respectively,once a day for 3 weeks.Three weeks later,24-hour urine was collected to measure urea nitrogen(SCr),and arterial blood was collected for serum creatinine(SUN).The rats were sacrificed,and their kidneys were weighed by laparotomy to calculate the kidney index(KI).HE staining and PAS were performed.The renal pathological changes were observed by staining,the fibrosis of renal tissues was observed by Masson staining,and the expression levels of TGF-β1,Smad2,AMPK,and LC3Ⅱproteins in the renal tissues were detected by immunohistochemical staining.Results Compared with the normal control group,the values of SCr,SUN,and KI in the model control group increased;the pathological changes of the renal tissues were obvious,and glomerular compensatory hypertrophy,mesangial matrix hyperplasia,and renal interstitial fibrosis were evident;the expression levels of TGF-β1 and Samd2 increased,while the expression levels of AMPK and LC3Ⅱdecreased(all P<0.05).Compared with the model control group,SCr,SUN,and KI,glomeruli,renal interstitial lesions,and fibrosis were reduced in the low-dose and high-dose ART groups.The improvement in the low-dose ART group was more obvious,and the expression of TGF-β1,and Samd2 protein in the kidney tissues decreased,and the expression of AMPK and LC3Ⅱincreased as compared with those of the high-d

关 键 词：糖尿病肾病 青蒿琥酯 肾纤维化 转化生长因子β1 SMAD2 单磷酸腺苷激活的蛋白激酶 LC3-磷脂-乙醇胺结合物 

分 类 号：R587[医药卫生—内分泌]