THE MECHANISM OF THE PI3K-AKT SIGNALLING PATHWAY INVOLVED IN REGULATING INTIMAL HYPERPLASIA IN ARTERIOVENOUS FISTULAS

QingQing Xu, Zhengrong Ma, WenMing Zhou*

Suzhou High Tech Zone People's Hospital, Suzhou 250109, Jiangsu Province, China

Objective: This study explores the important regulatory mechanism of the PI3K-AKT signalling pathway in arteriovenous fistula (AVF) vascular intimal hyperplasia. 

Methods: 45 SPF male rats were selected as research subjects. According to the random allocation table, the rats were divided into a blank control group (15 rats), an AVF group (15 rats) and a PI3K inhibition group (15 rats). The blank control group did not receive any treatment, the AVF group established the AVF model, and the PI3K inhibition group established the AVF model and used the PI3K inhibitor GDC0941. Blood vessel samples of each group were prepared, and the intimal hyperplasia of each group was observed with the HE staining method. Fluorescence quantitative PCR was used to detect the expression of PI3K and AKT mRNA in the three groups of specimens, the MTT experiment was used to detect cell proliferation activity, and the Transwell chamber method was used to detect cell migration ability. 

Results: In each rat of the blank control group, the vein structure was normal and the blood vessel consisted of a single layer of endothelial cells. The appearance and edges were flat and tightly arranged. Intravenous intimal hyperplasia was most prominent in the AVF group, which showed papillary hyperplasia and structural disorder with significant inflammatory cell infiltration, proliferative intimal necrosis, and obvious damage to the elastic membrane. In the PI3K inhibition group, the venous wall and intima were thickened, and the smooth muscle and extracellular matrix were proliferated. Observation of the outside of the media showed scattered inflammatory cell infiltration. Compared with the blank control group, the expression of PI3K and AKT mRNA in the AVF and PI3K inhibition groups was significantly increased (P<0.05). Compared with the AVF group, the expression of PI3K in the PI3K inhibition group was significantly reduced (P<0.05), and the expression of AKT was not statistically significant (P>0.05). Both the cell proliferation activity and cell migration ability of rats in the PI3K inhibition group were significantly lower than those of rats in the AVF group (P<0.05). 

Conclusion: The PI3K-AKT signalling pathway can promote the proliferation and migration of arteriovenous fistula vascular cells, affecting vascular intimal hyperplasia after AVFs.