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A14578 The Effect of A1AR on Systolic Blood Pressure by Inhibiting NLRP3/IL-1B in Type 1 Diabetic Mice

Objectives: Hypertension is one of the most important complications of diabetic nephropathy. In our previous study, we found adenosine type 1 receptor (A1AR) played a significant role in the progress of diabetic nephropathy. But whether A1AR was involved in the regulation of blood pressure remain unknown. In this study, we try to explore the effect of A1AR on blood pressure regulation in type 1 diabetic nephropathy and its possible mechanism. Methods: Type 1 diabetic nephropathy mice model was established by intraperitoneal injection of streptozotocin in wide and A1AR knock-out mice for 4 weeks. Systolic blood pressure was detected by tail artery blood pressure monitor, and urine and kidney samples were collected. A1AR, CD34, PDGFR, NLRP3 and IL1b were detected by immunohistochemistry staining and western blotting. Results: At 4 weeks, albuminuria (P = 0.002) and renal pathological lesion were observed in diabetic mice with activation of A1AR, lower systolic blood pressure (P = 0.003) than control mice. In A1AR knock-out diabetic mice, further aggravated albuminuria (P = 0.002) and increased systolic blood pressure (P = 0.004) were observed, along with the increased expression of inflammatory kinase pERK (1.38times, P = 0.0338), inflammasome nod-like receptor protein3 NLRP3 (2 times, P = 0.006) and it's downstream proinflammatory cytokine IL-1&bgr;. While the more decreasing expression of CD34 (peritubular capillary marker) and PDGFR (pericyte marker) were detected. This indicated much severe inflammation was existed to aggravate microvascular lesion in A1AR deficient diabetic mice Conclusion: A1AR played a protective role in blood pressure regulation by inhibiting NLRP3/IL1&bgr; pathway to prevent microvascular lesion in type 1 diabetic nephropathy.