高渗钠盐溶液复苏对严重烫伤大鼠早期肝脏损伤的影响

Effects of hypertonic sodium saline resuscitation on the liver damage of rats at early stage of severe scald

目的探讨高渗钠盐溶液复苏对严重烫伤大鼠早期肝脏损伤的影响。方法将56只SD大鼠按随机数字表法分为假伤组8只、乳酸钠林格液组24只与高渗钠盐组24只。假伤组大鼠模拟致假伤后不予补液，另2组大鼠致背部30%TBSA深Ⅱ～Ⅲ度烫伤。按Parkland公式补液，乳酸钠林格液组大鼠补充乳酸钠林格液，高渗钠盐组大鼠补充300 mmol/L钠离子溶液。假伤组于伤后即刻，另2组于伤后2、8、24 h，分别取8只大鼠，取腹主动脉血和肝脏。干湿质量法检测肝脏含水量，全自动生化分析仪测定血清中ALT、AST含量，ELISA法检测血清TNF－α、IL－1及高迁移率族蛋白B1（HMGB1）含量，紫外分光光度计检测肝脏丙二醛和SOD含量，HE染色观察肝脏病理变化。对数据行单因素方差分析和SNK检验。结果（1）伤后2、8、24 h，乳酸钠林格液组大鼠肝脏含水量均高于假伤组和高渗钠盐组（P〈0.05或P〈0.01）。（2）伤后2 h，3组大鼠血清ALT含量相近（P值均大于0.05）；伤后8、24 h，高渗钠盐组与乳酸钠林格液组大鼠血清ALT含量均高于假伤组（P〈0.05或P〈0.01），高渗钠盐组大鼠血清ALT含量低于乳酸钠林格液组（P值均小于0.01）。伤后2、8、24 h，高渗钠盐组与乳酸钠林格液组大鼠血清AST含量均高于假伤组（P值均小于0.01）；伤后2、8 h，高渗钠盐组大鼠血清AST含量低于乳酸钠林格液组（P〈0.05或P〈0.01）。（3）伤后2、8 h，乳酸钠林格液组大鼠血清TNF－α含量分别为（123±39）、（153±38）pg/mL，高于假伤组的（60±18）pg/mL和高渗钠盐组的（85±10）、（94±16）pg/mL（P值均小于0.01）；伤后8 h，高渗钠盐组大鼠血清TNF－α含量高于假伤组（P〈0.05）。伤后24 h，3组大鼠血清TNF－α的含量相近（P值均大于0.05）。伤后2、8、24 h，乳酸钠林格液组大鼠血清IL－1含量分别为（122±35）、（141±30）、（122±31）pg/mL，高渗钠盐组大鼠血清IL－1含量分别为（80±12）、（93±15）、（80±11）pg/mL，均高于假伤组的（40±17）pg/mL（P值均小于0.01）；高渗钠盐组大鼠血清IL－1含量均低于乳酸钠林格液组（P值均小于0.01）。伤后2 h，3组大鼠血清HMGB1的含量相近（P值均大于0.05）。伤后8、24 h，乳酸钠林格液组大鼠血清HMGB1含量分别为（0.386±0.146）、（0.590±0.188）ng/mL，高于假伤组的（0.050±0.027）ng/mL和高渗钠盐组的（0.143±0.038）、（0.309±0.095）ng/mL（P值均小于0.01）；伤后24 h，高渗钠盐组大鼠血清HMGB1含量高于假伤组（P〈0.01）。（4）伤后2、8、24 h，乳酸钠林格液组和高渗钠盐组大鼠肝脏丙二醛含量均高于假伤组，SOD含量均低于假伤组，P值均小于0.01；高渗钠盐组大鼠肝脏丙二醛含量均低于乳酸钠林格液组，SOD含量均高于乳酸钠林格液组，P值均小于0.01。（5）与假伤组比较，乳酸钠林格液组大鼠肝细胞伤后各时相点均可见大量脂肪样变，伤后8、24 h可见肝细胞水肿空泡；高渗钠盐组大鼠仅在伤后8、24 h出现少量肝细胞脂肪样变，且未见肝细胞水肿。结论与乳酸钠林格液相比，高渗钠盐溶液复苏可通过减少炎症介质产生，降低氧化应激程度等减轻严重烫伤大鼠早期的肝脏损伤。

ObjectiveTo explore the effects of hypertonic sodium saline （HSS） resuscitation on the liver damage of rats at early stage of severe scald.MethodsFifty-six SD rats were divided into sham injury group （SI, n=8）, lactated Ringer′s solution group （LRS, n=24）, and group HSS （n=24） according to the random number table. Rats in group SI were sham injured without resuscitation, while rats in the other two groups were reproduced deep partial-thickness to full-thickness scald model with 30% total body surface area on the back. Rats in group LRS were resuscitated with LRS, while rats in group HSS were resuscitated with 300 mmol/L sodium ion solution according to the Parkland formula. Blood of abdominal aorta and liver of 8 rats in group SI immediately post injury and in the other two groups at post injury hour （PIH） 2, 8, and 24 respectively were collected. Then liver water content was determined by dry-wet weight method. Serum content of alanine aminotransferase （ALT） and aspartate transaminase （AST） was detected by automatic biochemical analyzer. Serum content of tumor necrosis factor α （TNF-α）, interleukin-1 （IL-1）, and high mobility group box 1 （HMGB1） was determined by enzyme-linked immunosorbent assay. Liver content of malondialdehyde （MDA） and superoxide dismutase （SOD） was detected by ultraviolet spectrophotometer. Pathologic changes of liver were observed by HE staining. Data were processed with one-way analysis of variance and SNK test.Results（1） At PIH 2, 8, and 24, liver water content of rats in group LRS was higher than that in group SI and group HSS （P〈0.05 or P〈0.01）. （2） At PIH 2, serum ALT content of rats in the three groups was similar （with P values above 0.05）. At PIH 8 and 24, serum ALT content of rats in group HSS and group LRS was higher than that in group SI （P〈0.05 or P〈0.01）, and serum ALT content of rats in group HSS was lower than that in group LRS （with P values below 0.01）. At PIH 2, 8, and 24, serum AST content of rats in group HSS and group LRS was higher than that in group SI （with P values below 0.01）. At PIH 2 and 8, serum AST content of rats in group HSS was lower than that in group LRS （P〈0.05 or P〈0.01）. （3） At PIH 2 and 8, serum TNF-α content of rats in group LRS was （123±39） and （153±38） pg/mL respectively, higher than that in group SI [（60±18） pg/mL] and group HSS [（85±10） and （94±16） pg/mL respectively, with P values below 0.01]. At PIH 8, serum TNF-α content of rats in group HSS was higher than that in group SI （P〈0.05）. At PIH 24, serum TNF-α content of rats in the three groups was similar （with P values above 0.05）. At PIH 2, 8, and 24, serum IL-1 content of rats in group LRS was （122±35）, （141±30）, and （122±31） pg/mL respectively, and that in group HSS was （80±12）, （93±15）, and （80±11） pg/mL respectively, all higher than that in group SI [（40±17） pg/mL, with P values below 0.01]; serum IL-1 content of rats in group HSS was lower than that in group LRS （with P values below 0.01）. At PIH 2, serum HMGB1 content of rats in the three groups was similar （with P values above 0.05）. At PIH 8 and 24, serum HMGB1 content of rats in group LRS was （0.386±0.146） and （0.590±0.188） ng/mL respectively, higher than that in group SI [（0.050±0.027） ng/mL] and group HSS [（0.143±0.038） and （0.309±0.095） ng/mL respectively, with P values below 0.01]. At PIH 24, serum HMGB1 content of rats in group HSS was higher than that in group SI （P〈0.01）. （4） At PIH 2, 8, and 24, liver MDA content of rats in group HSS and group LRS was higher than that in group SI and their liver SOD content was lower than that in group SI （with P values below 0.01）; liver MDA content of rats in group HSS was lower than that in group LRS and their liver SOD content was higher than that in group LRS （with P values below 0.01）. （5） Compared with those of rats in group SI, liver cells of rats in group LRS showed massive steatosis at each time point, and liver cell-edema appeared at PIH 8 and 24; while liver cells of rats in group HSS showed little steatosis only at PIH 8 and 24, and the liver cell-edema never appeared.ConclusionsCompared with LRS, HSS resuscitation can alleviate liver injury of rats at the early stage of severe scald through relieving inflammatory mediators and reducing degree of oxidative stress, etc.