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Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats.
BMC Complementary and Alternative Medicine ( IF 4.782 ) Pub Date : 2019-12-05 , DOI: 10.1186/s12906-019-2728-9
Yuyan Fan 1 , Hongyu Fan 2 , Bin Zhu 3 , Yilun Zhou 4 , Qingshan Liu 5 , Ping Li 6
Affiliation  

BACKGROUND Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS). METHODS DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro. RESULTS Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment. CONCLUSIONS These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

中文翻译:

黄芪甲苷IV通过激活链脲佐菌素糖尿病诱导的大鼠中的eNOS来预防糖尿病性肾病。

背景技术据报道,黄芪甲苷IV(AS-IV)在改善糖尿病性肾病(DN)中起作用,但是,其潜在机制仍不清楚。本研究的目的是研究AS-IV是否通过调节内皮一氧化氮合酶(eNOS)改善DN。方法腹腔注射65 mg / kg链脲佐菌素(STZ)诱导Sprague-Dawley(SD)雄性大鼠DN模型。连续八周给AS-IV治疗组的大鼠口服5 mg / kg /天或10 mg / kg /天的AS-IV。测量体重,血糖,血尿素氮(BUN),血清肌酐(Scr),蛋白尿和糖基化血红蛋白(HbA1c)水平。苏木-伊红(HE)和高碘酸席夫(PAS)染色用于检测肾脏病理。通过TUNEL法测定肾小球细胞的凋亡状态。通过蛋白质印迹检测eNOS的磷酸化和乙酰化。还在体外研究了人肾小球内皮细胞(HRGEC)中AS-IV对高糖(HG)诱导的细胞凋亡和eNOS活性的影响。结果AS-IV治疗可明显减轻糖尿病大鼠的DN症状,这可通过降低BUN,Scr,蛋白尿,HbA1c水平和扩大肾小球系膜基质来证明。AS-IV处理还促进了血清和肾脏组织中一氧化氮(NO)的合成,并改善了Ser 1177处eNOS的磷酸化,同时降低了eNOS的乙酰化程度。此外,HG诱导的HRGECs功能障碍包括细胞通透性和凋亡增加,Ser 1177的eNOS磷酸化受损以及NO生成减少,都被AS-IV治疗逆转了。结论这些新发现表明,AS-IV通过抑制eNOS的乙酰化并激活其在Ser 1177处的磷酸化来改善DN的功能异常。AS-IV可以作为DN的潜在治疗药物。
更新日期:2019-12-05
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