| Objective:To observe the effect of6%hydroxyethyl starch (130/0.4)(Voluven) on LPS-induced endotoxin shock rabbit renal function, and to explore its possible mechanism.Methods:36New Zealand white rabbits were randomly divided into control group (C, n=6), model group (S, n=6), the treatment group (n=24)(Ringer group (R), Voluven lOml/kg group (H1), Voluven20ml/kg group (H2) and Voluven30ml/kg group (H3), each group was6rabbits). All animals were given tracheotomy, mechanical ventilated and PiCCO hemodynamic monitored. Stable after the operation for30minutes, model group and treatment group were infused by the left ear vein2mg/kg dilution of E. coli LPS to induce endotoxin shock model, while the control group with the same dose of saline, infused time were controlled about30min. All rabbits were given saline4ml/kgh to maintain physiological requirements. After the endotoxin shock model established, R group and H1, H2, H3groups were given fluid therapy with Ringer’s solution and hydroxyethyl starch respectively, and given norepinephrine to maintain tissue perfusion pressure. At baseline time (Tx), model time (TO), liquid treatment for3hours (T3), and liquid treatment for6hours (T6) four time points, respectively,to monitor each rabbit’s systemic hemodynamics status, adjust the ventilator parameters based on the results of blood gas, and collect blood and urine samples to detect sNGAL, uNGAL and SCr. Taked kidney tissue after T6to observe the structure of renal tissue pathology by optical microscopy and transmission electron microscopy.Results:Rabbit’s MAP appeared to decline after infusion of LPS, and TO’s MAP decreased about40mmHg when compared with Tx, and the difference was statistically significant (p <0.05). HR, SVV value continued to rise, and the CI, GEDVI, ITBI, dPmax all progressive decline, and all the differences were statistically significant (p<0.05). SVRI appeared to a transient rise trend before TO, then characterized by declining trend until the application of norepinephrine. EVLWI, PVPI, CVP did not change significantly, and there was no statistically difference(p>0.05). MAP, CI, SVRI, GEDVI, ITBI and dPmax of treatment group rose in varying degrees after receiving fluid resuscitation and vasoactive drugs, while to T6almost returned to basal levels. HR and SVV gradually declined during the treatment, which reached to a stable level at T6; while EVLWI and PVPI increased in varying degrees during treatment, especially in R group, which compared with other groups the differences were statistically significant (p<0.05). H3was the least liquid infusion group while compared with the other treatment groups, and differences were statistically significant (p<0.05). The application of norepinephrine in H2and H3groups were less than other two groups, and the differences were statistically significant while compared with H1, R group(p<0.05). The result of blood gas analysis showed:after infusion of LPS, the PH decreased, Lac increased, while HCT change little, and the difference was no statistically significant (p<0.05). Model group showed the severe acidosis at the end of experiment, and even lead some rabbits to death. PH increased and Lac value dropped in the treatment group after the treatment, and all the differences were statistically significant(p<0.05). HCT manifested in decline trend during treatment, especially in H3group, which compared with the other groups the differences were statistically significant (p<0.05). The differences of PO2, PCO2and SaO2within each group in observation time were no statistically significant (p>0.05). The total amount of urine in control group was more than the model group, and the difference was statistically significant (p<0.05); the amout of urine of H3group was a little more than other treatment groups, and the differences were no statistically significant(p>0.05). After the infusion of LPS, SCr, uNGAL and sNGAL of model and treatment group appeared to rise. SCr rose slowly, and there were no statistically significant between treatment groups (p>0.05); sNGAL rose faster than the uNGAL, but the difference was not statistically significant (p>0.05); there was no correlation between sNGAL and uNGAL whether at T3or at T6time point(r=0.767, p=0.075; r=0.698, p=0.302). Observe kidney tissue by optical microscopy and transmission electron microscopy showed:the kidney from control group showed normal glomeruli and tubules, complete and clear cells and organelles, and dyeing uniform cytoplasm; in contrast, in model group the kidney showed edema in glomerular capillary endothelial cells, vacuoles in cytoplasmic, and inflammatory cells in the mesangial stroma and renal interstitium, but there were no obvious abnormal in basement membrane, foot cells, and foot process. Although renal tubule of model group appeared edema, smaller lumen, epithelial cell vacuoles change, cell shrinkage, chromatin condensed, cell nuclei cracking, visible apoptotic body and cell boundaries were not clear, there was no necrosis had been found; meanwhile, microvilli partial deletion, loss, disturbance, and intracellular lysosomes and phagocytic cells increased in proximal tubule epithelial cell cavity surface. The pathological damage of glomerular, glomerular mesangial interstitial area and renal tubules in the treatment group(R, H1, H2, H3) are lighter than model group; there was no obvious abnormal pathological changes in hydroxyethyl starch group(H1, H2, H3), which compared with R group in glomerular filtration membrane area and renal tubular epithelial cells area.Conclusions:1, LPS can be used to induce New Zealand white rabbits endotoxin shock model, which can further lead to the occurrence of endotoxin shock AKI.2, uNGAL showed rise in the early period of AKI induced by LPS, which can provide the theory basis for diagnosis of AKI caused by endotoxin shock.3, Application of Ringer and6%hydroxyethyl starch (130/0.4)(Voluven) could improve hemodynamics and tissue perfusion in the endotoxin shock rabbit model; meanwhile, liquid treatment could protect the renal function in certain extent.4,6%hydroxyethyl starch (130/0.4)(Voluven) did not lead to endotoxin shock rabbit renal function further injury which compared with the ringer’s liquid.
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