組織型kallikrein蛋白在缺氧/再灌流腎臟傷害的藥理作用

Kallikrein/kinin has been shown to be beneficial in ischemia/reperfusion injury in heart but is detrimental in lung, liver and intestine. In the present study, we examined the effect of rat kallikrein protein in renal ischemic/reperfusion. The result was opposite to the hypothesis we previously provided. Adult male Wistar rats were subjected to 40 minutes of occlusion of renal artery followed by reperfusion. Rats were given tissue kallikrein protein 5 days before ischemia till sacrifice (pre-treat group) or immediately after initiation of reperfusion (treat group). The results revealed that pre-treat group had worst renal function impairment, followed by treat group, then control group (Figure 1). Morphological analyses also showed that kallikrein enhanced the tubular necrosis (Figure 2) and attracted more inflammatory infiltration in the cortex and medulla (Figure 3). Gene expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 were higher in kallikrein treated rats (Figure 4). In vivo chemiluminescence method for measurement of reactive oxygen species (ROS) generation revealed that ROS generation was augmented by kallikrein protein administration in both ischemic and reperfusion phases (Figure 5). All these deleterious effects of kallikrein on ischemic/reperfusion renal injury were reversed by co-treatment with bradykinin receptor B2 antagonist and was not through the pathways of systemic hemodynamic or volume status change. The study indicated early activation bradykinin receptor B2 had deleterious effects on ischemic/reperfusion renal injury in both ischemic and reperfusion phases. The findings suggest the possible application of bradykinin receptor antagonist in the acute ischemic renal disease associated with bradykinin activation