Abstract | BACKGROUND: 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.
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Authors | Yuyan Fan, Hongyu Fan, Bin Zhu, Yilun Zhou, Qingshan Liu, Ping Li |
Journal | BMC complementary and alternative medicine
(BMC Complement Altern Med)
Vol. 19
Issue 1
Pg. 355
(Dec 05 2019)
ISSN: 1472-6882 [Electronic] England |
PMID | 31805910
(Publication Type: Journal Article)
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Chemical References |
- Blood Glucose
- Protective Agents
- Saponins
- Triterpenes
- Nitric Oxide
- astragaloside A
- Nitric Oxide Synthase Type III
- Nos3 protein, rat
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Topics |
- Animals
- Blood Glucose
(drug effects)
- Diabetes Mellitus, Experimental
(metabolism)
- Diabetic Nephropathies
(metabolism, pathology)
- Kidney
(drug effects, pathology)
- Male
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Protective Agents
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Saponins
(pharmacology)
- Signal Transduction
(drug effects)
- Triterpenes
(pharmacology)
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