Effects Of Mild Hypothermia On Early Inflammation And Oxidative Stress In Mice With Sepsis Associated Acute Kidney Injury

Objective To observe the effect of mild hypothermia on the early inflammatory reaction and mitochondrial damage induced by oxidative stress in mice with acute kidney injury induced by sepsis,and to explore whether mild hypothermia has protective effect on sepsis associated acute kidney injury.Methods The 48 male mice were randomly divided into three groups,the mice is purchased from the experimental animal center of the school,feeding on the standard terms and conditions.All the mice were divided into sham opration group,sepsis model group and the mild hypothermia group,witn 16 mice in each group.Each big group is divided into six hours and 24 hours after postoperative two groups,witn 8 mice in each group.In the sham operration group,cecal ligation and perforation were not performed.The mice were opened and turned over at room temperature,and then closed and sutured.In the sepsis model group,cecal ligation and perforation were performed after laparotomy at room temperature.The mild hypothermia group received mild hypothermia intervention(33-35℃)after surgery,the temperature was recovered at the rate of0.2-0.5℃ per hour,the target of temperature resuscitation was 36℃,using ice bag and animal constant temperature system to implement mild hypothermia.The pathological changes and renal injury scores were observed 24 hours after surgery by hematoxylin-eosin staining(HE).The concentrations of TNF-α、IL-1β、IL-18、NGAL、MAD、SOD and Cyt C in renal tissues were measured 6hours and 24 hours after surgery by enzyme-linked immunosorbent assay(ELISA).Using Western blot immune protein imprinting method to detect Caspase 3、Bax、Bcl-2 protein expression level;In addition to protein picric acid colorimetry,diacetyl oxime method to detect serum creatinine and urea nitrogen.Result(1)The kidney tissue pathologic result shows: the pathological damage of mild hypothermia group was less than that of sepsis model group;the kidney injury score at 24 hours and 6 hours after operation in mild hypothermia group were lower than those in sepsis model group(P < 0.05).(2)The level of TNF-α、IL-1β、IL-18 of mild hypothermia group and sepsis model group was higher than in sham operation group;the level of TNF-α、IL-1β、IL-18 of mild hypothermia group was lower than that of sepsis model group at the same time(P < 0.05).(3)The level of MDA、Cyt C、NGAL of mild hypothermia group and sepsis model group was higher than of sham operation group;the level of SOD was lower than that of sham operation group;The level of MDA、Cyt C、NGAL of mild hypothermia group was lower than that of sepsis model group at the same time,the level of SOD of mild hypothermia group was lower than that of sepsis model group at the same time(P < 0.05).(4)The protein expression level of Bax、Caspase-3 of mild hypothermia group and sepsis model group was higher than of sham operation group;The protein expression level of Bc1-2 was lower than that of sham operation group;The protein expression level of Bax、Caspase-3 of mild hypothermia group was lower than that of sepsis model group at the same time,The protein expression level of Bc1-2 was of mild hypothermia group was lower than that of sepsis model group at the same time(P < 0.05).(5)The level of creatinine and urea nitrogen of mild hypothermia group and sepsis model group was higher than of sham operation group;The level of postoperative serum creatinine and urea nitrogen of mild hypothermia group was lower than that of epsis model group at the same time(P < 0.05).Conclusion(1)Inflammatory reaction and oxidative stress leads to mitochondrial damage of renal tubular epithelial cells and sepsis related acute kidney injury.(2)Mild hypothermia may protect the kidney of mice with acute kidney injury induced by inhibiting the inflammatory response and oxidative stress response and reducing the damage of mitochondria and apoptosis of renal tubular epithelial cells.