ROLE OF NLRP3 INFLAMMATORY CORPUSCLES AND IL-18 IN PATHOGENESIS OF SEPSIS-RELATED ACUTE KIDNEY INJURY

Shufang Chen*, Xiaohong Gong**, Xiangdong Li*, Cuicui Wang*, Yan Chen*, Yue Zhao*, Hong Wang*, Chuang Sun***, #

*Department of Emergency, The Second Hospital of Dalian Medical University, Dalian, PR China - **Department of Laboratory, Dalian Hospital of Traditional Chinese Medicine, Dalian, PR China - **Department of Radiology, The Second Hospital of Dalian Medical University, Dalian, PR China

Objective: To analyze the role of NLRP-3 inflammatory corpuscles and IL-18 in the pathogenesis of sepsis-related acute kidney injury (AKI). 

Method: Sixty healthy male SPF rats were randomly divided into either sham operation or sepsis model groups at 6, 12, 24, 48 and 72 hours. A cecum ligation and perforation method was used to prepare a sepsis model in six groups. The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) in renal tissues of rats in each group were detected by an automatic biochemical analyzer. The expression of NLRP3, ASC and Caspase-1 in renal tissues of each group was determined by Western blotting. The changes of expression were detected by immunohistochemistry. Changes of NLRP3, ASC and Caspase-1 positive cells were assayed using immunohistochemistry. The levels of interleukin-18 (IL-18) in each group were determined by ELISA. 

Results: Compared with the sham-operated group, BUN and Scr levels in kidney tissues of rats in each model group increased significantly after caecal ligation and perforation (P<0.05), and increased gradually with the prolongation of operation time. Hence, the sepsis AKI model was successfully established. Compared with the sham-operated group, the levels of NLRP3, ASC and Caspase-1 protein in each model group began to increase with time at 6 hours after operation (P<0.05), and tended to stabilize at 24 hours after operation (P>0.05). Compared with the sham-operated group, the number of NLRP3, ASC and Caspase-1 positive cells in each model group began to increase with time at 6 hours after operation (P<0.05). Compared with the sham-operated group, the IL-18 level of rats in each model group began to increase at 6 hours after operation (P<0.05), and decreased gradually at 24 hours after operation (P<0.05). 

Conclusion: The increased expression of NLRP3 inflammatory corpuscles in rat sepsis AKI model leads to a series of inflammatory reactions, resulting in elevated levels of IL-18 in serum, which aggrava