Regulatory effect of ulinastatin on NF-κB and MMP-2/TIMP-2 in rats with acute renal trauma / 第二军医大学学报

ABSTRACT

Objective: To investigate the expression of nuclear factor-κB (NF-κB), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2(TIMP-2) in the kidneys of rats with acute renal trauma, and to discuss the influence of ulinastatin on their expression and its protective mechanism on the kidney. Methods: The animal model was established by striking the rachi-costaz zone with falling object from the height of 45 cm. Sixty-six rats were randomly divided into three groupsnormal control group (C,n = 6),trauma group (TRA,n = 30),and ulinastatin+trauma (UTI,n = 30); the last 2 groups were further divided into 1 h, 6 h, 12 h, 18 h and 24 h subgroups, with 6 animals at each time point. Tissue microarray and immunohistochemistry were used to examine the expression of NF-κB and MMP2/TIMP-2 in different groups. Results: MMP-2 and NF-κB began to express 1 h after trauma in TRA group and their expression was significantly stronger than that in the control group (P < 0.05, P < 0.01); their expression reached the peaks at 12 h and 6 h after trauma and then gradually decreased. The expression of MMP-2 and NF-κB in UTI group reached their peaks 18 h and 12 h after trauma,respectively,and was significantly higher than that in the control group(P<0.01),but was lower than that in the TRA group at corresponding time points(P<0.01,P<0.05). The expression of TIMP-2 was significantly stronger than that in the control group and TRA group at 6 h, 12 h and 18 h after trauma(P<0.01,P<0.05). Conclusion: The expression of NF-κB,MMP-2 is increased in acute traumatic tissue of the kidney; the increase of TIMP-2 is not evident. Ulinastatin can protect the kidney by inhibiting the expression of MMP-2 and NF-κB and maintaining the balance of MMP-2/TIMP-2.