Correlation of kidney injury and inflammatory response in rats with classic severe heatstroke / 中华危重病急救医学

ABSTRACT

ObjectiveTo investigate the temporal features of renal injury in rats with severe heat stroke (SHS) and their relationship with inflammatory response.Methods Fifty-six male Wistar rats were randomly divided into normal control group and SHS for 0, 2, 6, 24, 48, 72 hours group (SHS-0, 2, 6, 24, 48, 72 h groups), with 8 rats in each group. Rats were placed in an artificial climate chamber [temperature (39.5±0.2)℃, humidity (60±5)%] to induce SHS model, and the criterion for successful model reproduction was the onset of lowering peak systolic blood pressure (SBP). Then the rats were transferred to room temperature (23.0±0.2)℃ after successful reproduction of the model. The rats of normal control group were kept in room temperature of (23.0±0.2)℃. Heart blood and renal tissue samples were harvested, and the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were determined by automatic biochemistry analyzer. The levels of myeloperoxidase (MPO), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in renal tissue specimens were determined by enzyme linked immunosorbent assay (ELISA). The changes in histopathology in kidney were observed with light microscopy, and Paller scores were used to assess the degree of renal injury.Results Compared with normal control group, the levels of SCr and BUN in serum, and MPO, TNF-α and IL-6 in the renal tissue homogenate were significantly increased in SHS-6 h group [SCr (μmol/L) 174.0±27.0 vs.68.0±11.3, BUN (mmol/L) 12.6±2.3 vs. 4.3±1.2, MPO (203.0±38.0)% vs. (100.0±1.4)%, TNF-α (121.0±16.0)% vs. (100.0±1.4)%, IL-6 (118.0±19.0)% vs. (100.0±1.3)%, allP< 0.05], and they peaked at 24 hours [SCr (μmol/L) 489.0±96.0 vs. 68.0±11.3, BUN (mmol/L) 19.3±5.7 vs. 4.3±1.2, MPO (511.0±41.0)% vs. (100.0± 1.4)%, TNF-α (399.0±47.0)% vs. (100.0±1.4)%, IL-6 (473.0±56.0)% vs. (100.0±1.3)%, allP< 0.01], then declined to the normal levels at 72 hours. Under light microscopy, tissue edema and necrosis of renal tubules were found, and leukocyte infiltration was found to be most profuse at 24 hours, then they returned to normal levels at 72 hours. Paller scores in SHS-6 h group were significantly higher than those of the normal control group (75.45±9.70 vs. 14.23±3.26,P< 0.01), and it peaked at 24 hours (186.00±14.25 vs. 14.23±3.26,P< 0.01), followed by a gradual lowering, back to normal level at 72 hours.ConclusionThe results suggest that progressive renal damage occurred in the rats with SHS within 24 hours, and it was accompanied with elevated levels of MPO, TNF-α and IL-6 in the kidney homogenate, suggesting that inhibition of neutrophil activation and the release of IL-6, TNF-α may protect the SHS associated renal injury.