ADIPONECTIN PROTECTS THE KIDNEY THROUGH THE AKT/AMPK/ENOS SIGNALLING PATH- WAY IN THE BLOOD VESSELS OF DIABETIC MODEL RATS

TIAN MENG^1,2, KANG LILI², HAN HONGLING¹

¹Tianjin Medical University General Hospital, Tianjin 300052 - ²Internal Medicine of Xianshuigu Hospital Jinnan District of Tianjin, Tianjin 300350, China

Objective: To explore the mechanism by which adiponectin protects the kidney through the vascular Akt/AMPK/eNOS signalling pathway in diabetic model rats.

Methods: Overall, 72 rats were randomly divided into the normal control group (NC group), the diabetes mellitus group (DM group), the pIRES2-EGFP-gAd plasmid transfected adiponectin interference group (ADPN group) and the pIRES2-EGFP transfected empty vector group (DP group). Except for the NC group, the animals were fed a high fat and high sugar diet for 4 weeks and streptozo- tocin was injected intravenously to establish a diabetic rat model. Rats in the ADPN group and DP group were intraperitoneally injected with the pIRES2-EGFP-gAd plasmid transfection complex and the pIRES2-EGFP transfection complex, respectively. The general situa- tion of rats was observed and the urine protein, blood glucose level and HbA1c were measured in each group after 8 weeks. The western blot assay was used to detect the relative expression of protein kinase B (Akt), adenosine monophosphate activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) in rat blood vessels. The pathologic condition of renal tissue sections of rats was observed by HE staining, and the levels of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum of rats were deter- mined by an enzyme-linked immunosorbent assay (ELISA).

Results: Nine rats died during modelling. The levels of urine protein, blood glucose, HbA1c, TNF-α and IL-1β in the DM, DP and ADPN groups were significantly higher than those in the NC group, with a difference that is statistically significant (P<0.05). The levels of urine protein, blood glucose, HbA1c, TNF-α and IL-1β in the ADPN group were significantly lower than those in the DM and DP groups, with a difference that is statistically significant (P<0.05). Compared with the NC and ADPN groups, the expression level of Akt, AMPK and eNOS in the DM and DP groups was significantly lower than that in NC and ADPN groups, with a difference that is statisti- cally significant (P<0.05). Compared with the NC group, the glomerular diameter enlarged, the basement membrane thickened, diffuse hyperplasia occurred in the mesangium, renal tubular epithelial cells and microvilli fell off, and vacuolar degeneration was observed in the DM and DP groups. The pathological changes in the ADPN group were lighter than those in the DM group and the DP group.

Conclusion: Adiponectin can regulate the blood glucose levels in diabetic model rats and protect the kidney by up-regulating the expression of proteins in the Akt/AMPK/eNOS pathway in the blood vessels of diabetic model rats.