Abstract:Objective To investigate the effects and possible mechanisms of intervening P2X7 receptors on ischemia/reperfusion (I/R)-induced renal fibrosis. Methods Ten male wild-type C57BL/6 mice were randomly assigned to the sham operation group (WT-Sham) and the renal ischemia-reperfusion injury(IRI) group (WT-I/R). Ten P2X7 receptors gene knockout mice were also randomly assigned to the sham operation group (KO-Sham) or the renal IRI group (KO-I/R), with five mice in each group. The renal IRI model was established by unilateral nephrectomy and contralateral renal pedicle clamping. In the sham operation group, mice underwent renal pedicle localization without nephrectomy or clamping. Renal tissue specimens were collected after 42 days of reperfusion or sham operation. PAS staining was used to observe changes in renal tissue structure, Picrosirius Red staining was used to assess the degree of renal fibrosis, Western blot was performed to detect the expression of renal calcium-adhering protein E-cadherin and α-smooth muscle actin （α-SMA）, and immunohistochemical staining was used to observe the infiltration of F4/80-positive macrophages in the kidneys. Results After 42 days of renal IRI, PAS staining showed tubular atrophy and significant infiltration of inflammatory cells in the interstitium, while Picrosirius Red staining indicated obvious renal fibrosis. Compared with wild-type mice, P2X7 receptors gene knockout mice showed reduced tubular atrophy, decreased infiltration of inflammatory cells, and improved renal fibrosis. Western blot results showed that compared to the sham operation group, WT-I/R mice had decreased expression of the tubular marker E-cadherin and increased expression of the fibrosis marker α-SMA (P＜0.05). Compared to WT-I/R mice, KO-I/R mice showed improvement in E-cadherin decrease and α-SMA increase (P＜0.05). Immunohistochemical results revealed increased infiltration of macrophages in the kidneys after 42 days of renal IRI, while P2X7 receptors gene knockout mice showed reduced macrophage infiltration. Conclusion Renal IRI can lead to macrophage infiltration and fibrosis in renal tissue. Intervention of P2X7 receptors can reduce macrophage infiltration caused by IRI, improve renal tissue fibrosis, and delay the progression of chronic kidney disease.