The Early Diagnostic Efficacy of Serum Histone H3 in Rabbit Urosepsis Model

Abstract

Objective. We want to explore the changing law of circulating histones in the acute stage of urosepsis and to find more sensitive and specific biomarkers for diagnosing urosepsis as early as possible. Methods. Twenty healthy male New Zealand rabbits were randomly divided into 4 groups ( $N=5$ ): the control group, sham group, model group of LPS 600 μg/kg, and model group of LPS 1000 μg/kg. Heart rate (HR), respiration rate (RR), rectal temperature (T), and mean arterial pressure (MAP) were examined at 1, 3, 6, 12, and 24 hours after operation. Besides, peripheral blood cell counts (RBC, WBC, PLT, and Hb) and C reaction protein (CRP) were tested at 1, 3, and 6 hours after operation, while the levels of histone H3, MMP-9, TIMP-1, and procalcitonin (PCT) in the serum were tested at 1, 3, and 6 hours after operation by ELISA. The heart, left lung, liver, and left kidney were harvested for HE stain and observed to research the pathological change of these tissues. Results. (1) The general status of rabbits: rabbits in the control and sham groups came out in 2 h after operation and regain to drink and eat in 12-24 h after operation. State of the rabbits in the control group was better than that in the sham group. Rabbits in the model groups were languid after operation and stopped to drink and eat. (2) Vital signs of rabbits: there was no statistic difference in HR ( $P=0.238$ ) and RR ( $P=0.813$ ) among all groups. MAP of the model groups decreased at 3 h postoperative, but transient ( $P<0.001$ ). The T of the LPS 1000 group decreased at 6 h postoperative ( $P=0.003$ ). (3) The change of biomarkers: H3 level of the LPS groups in the serum increased at 1 h postoperative ( $P<0.01$ ); MMP-9 of the LPS 1000 group increased at 1 h postoperative ( $P<0.01$ ); WBC of the model groups decreased at 3 h postoperative ( $P<0.05$ ); PLT of the LPS 1000 group is significantly increased at 1 h postoperative ( $P<0.05$ ); no statistic difference was found in CRP, PCT, and TIMP-1 among all groups. (4) Pathological sections: no abnormal performance was found in the control and sham groups. Glomerulus of the model groups was out of shape and necrosis with obvious renal tubule expansion. Pulmonary pathology showed alveolar septum diffuse increased and inflammatory infiltrate. Change of the LPS 1000 group was more serious than that of the LPS 600 group. Conclusions. Ligating the ureter after an injection of 1000 μg/kg LPS into the ureter of the rabbit can establish the animal model of urosepsis. Histone H3 increase immediately at 1 h postoperative and are promised to be biomarkers of urosepsis, which are more effective than WBC, CRP, and PCT.