探讨丙戊酸钠对重度烧冲复合伤休克延迟补液大鼠内脏组织灌流和生存率的影响。

共360只雄性SD大鼠，(1)实验一，选择300只大鼠，按照随机数字表法分为假伤＋延迟补液组(SD组，n＝50)、假伤＋丙戊酸钠＋延迟补液组(SPD组，n＝50)、烧冲复合伤＋延迟补液组(BD组，n＝100)、烧冲复合伤＋丙戊酸钠＋延迟补液组(BPD组，n＝100)。SD组和SPD组大鼠37 ℃水浴浸泡背部12 s，腹部6 s；BD组和BPD组先用5 g高爆炸药距离大鼠50 cm爆炸致中度冲击伤，然后立即94 ℃沸水浸泡背部12 s，腹部6 s，致50%总体表面积Ⅲ度烧伤；SPD组和BPD组伤后即刻皮下注射丙戊酸钠(300 mg/kg)。SD组、SPD组、BPD组和BD组于伤后6、24 h分别按照Parkland公式腹腔内注射0.9%氯化钠溶液进行补液。于伤后即刻，伤后6、24、48、72 h 5个时间点，每个时间点均从SD组、SPD组、BD组、BPD组选择10、10、20、20只大鼠进行各脏器血流量和血气分析。(2)实验二，选取剩余的60只大鼠，按随机数字表法也分为SD组(n＝10)、SPD组(n＝10)、BD组(n＝20)、BPD组(n＝20)。于造模前48 h进行颈动脉置管。各组大鼠造模、处理同实验一操作。于伤后即刻，伤后6、24、48、72 h 5个时间点，检测各组大鼠平均动脉压(MAP)，同时计算各组大鼠生存率。数据比较采用单因素方差分析、t检验、log-rank检验和χ²检验。

实验一结果显示：(1)伤后即刻，4组肝脏、肾脏和小肠黏膜血流量比较，差异均无统计学意义(P值均大于0.05)；伤后6 h，4组肝脏、肾脏和小肠黏膜血流量组间总体比较，差异均有统计学意义(F＝463.45、267.27、449.64，P值均小于0.05)，BPD组与BD组肝脏、肾脏和小肠黏膜血流量比较，差异均无统计学意义(P值均大于0.05)；伤后24 h，4组肝脏、肾脏和小肠黏膜血流量组间总体比较，差异均有统计学意义(F＝1 347.52、125.23、1 210.84，P值均小于0.05)，BPD组与BD组肝脏、肾脏和小肠黏膜血流量比较，差异均有统计学意义(t＝89.72、6.57、10.23，P值均小于0.05)；伤后48 h，4组肝脏、肾脏和小肠黏膜血流量组间总体比较，差异均有统计学意义(F＝1 044.13、20.69、174.35，P值均小于0.05)，BPD组与BD组肝脏和小肠黏膜血流量比较，差异均有统计学意义(t＝51.90、34.72，P值均小于0.05)，肾脏血流量比较差异无统计学意义(t＝0.37，P>0.05)；伤后72 h，4组肝脏、肾脏血流量组间总体比较，差异均有统计学意义(F＝328.27，16.01，P值均小于0.05)，小肠黏膜血流量比较，差异无统计学意义(P>0.05)，BPD组与BD组肝脏血流量比较，差异有统计学意义(t＝25.32，P<0.05)，肾脏血流量比较，差异无统计学意义(P>0.05)。(2)伤后即刻和伤后48 h，4组pH值组间总体比较，差异均无统计学意义(P值均大于0.05)；伤后6、24、72 h，4组pH值组间总体比较，差异均有统计学意义(F＝54.48、5.68、1.98，P值均小于0.05)，伤后6、24 h，BPD组与BD组pH值比较差异均有统计学意义(t＝5.32、3.51，P值均小于0.05)，伤后72 h，2组pH值比较差异无统计学意义(P>0.05)；伤后即刻、伤后6、24 h，4组氧分压组间总体比较，差异均有统计学意义(F＝26.55、16.34、2.37，P值均小于0.05)，伤后即刻BPD组和BD组氧分压比较差异无统计学意义(P>0.05)，伤后6、24 h 2组比较差异均有统计学意义(t＝4.58、0.62，P值均小于0.05)；伤后48、72 h，4组血乳酸组间总体比较，差异均无统计学意义(P值均大于0.05)，伤后即刻、伤后6、24 h，4组血乳酸总体比较，差异均有统计学意义(F＝3.12、61.67、50.83，P值均小于0.05)，伤后即刻BPD组和BD组氧分压比较，差异无统计学意义(P>0.05)，伤后6、24 h, 2组比较差异均有统计学意义(t＝6.98、3.56，P值均小于0.05)。实验二结果显示：(1)伤后即刻和伤后72 h，4组MAP总体比较差异均无统计学意义(P值均大于0.05)，伤后6、24、48 h，4组MAP总体比较差异均有统计学意义(F＝292.73、104.29、5.01，P值均小于0.05)，BPD组与BP组MAP比较，差异均有统计学差异(t＝6.02、6.70、1.24，P值均小于0.05)。(2)伤后72 h，BPD组和BD组的生存率分别为70%和50%，2组比较差异有统计学意义(χ²＝11.03，P<0.05)。

丙戊酸钠复合延迟补液能显著增加重度烧冲复合伤休克大鼠肝脏、肾脏和肠道血流灌注，维持伤后早期的血压稳定，降低血乳酸水平，改善伤后72 h存活率。

To investigate the effects of sodium valproate on visceral tissue perfusion and survival rate of abdominal organs in rats with delayed fluid resuscitation after severe burn-blast combined injury.

A total of 360 male SD rats, (1) Experiment one, 300 rats were selected and divided into sham injury + delayed fluid resuscitation group (SD group, n=50), sham injury + sodium valproate + delayed fluid resuscitation group (SPD group, n=50), burn-rush combined injury + delayed fluid resuscitation group (BD group, n=100) and burn-rush combined injury + sodium valproate + delayed fluid resuscitation group (BPD group, n=100) according to the random number table method. The SD group and SPD group were soaked the back of rats in the 37 ℃ water for 12 s and the abdomen for 6 s. The BD group and BPD group were blasted with 5 g high explosive at a distance of 50 cm from the rat to cause moderate impact injury, and then immediately immersed the back of rats in boiling water at 94 ℃ for 12 s, abdominal for 6 s, causing 50% total body surface area of full thickness burns. SPD group and BPD group were injected subcutaneously with sodium valproate (300 mg/kg) immediately after injury. SD group, SPD group, BPD group and BD group were injected intraperitoneally with 0.9% sodium chloride solution according to the Parkland formula at 6, 24 h after injury for rehydration. Immediately after the injury, 6, 24, 48, 72 h after injury, each time point 10, 10, 20, 20 rats were selected from the SD group, SPD group, BD group, BPD group for visceral blood flow and blood gas analysis. (2)Experiment two, the rest of the 60 rats were divided into 4 groups according to the random number table method: SD group(n=10), SPD group(n=10), BD group(n=20) and BPD group(n=20). The modeling and treatment of the rats in each group was the same as experiment one. Carotid arteries were placed in all rats 48 h before modeling. The mean arterial pressure (MAP) of rats in each group was measured at 5 time points immediately after injury and at 6, 24, 48, 72 h after injury, and the survival rate of each group was also calculated. Data were processed with one-way analysis of variance, t text, the log-rank test and χ² test.

The results of experiment one showed: (1) Immediately after injury, there were no statistically significant differences in the blood flow of liver, kidney and small intestine mucosa in the 4 groups (with P values above 0.05). At 6 h after injury, the SD group, SPD group, BD group, and BPD group had statistically significant differences in overall comparison of the liver, kidney, and small intestinal mucosal blood flow groups (F=463.45, 267.27, 449.64; with P values below 0.05). There were no statistically significant differences in blood flow of liver, kidney and small intestine mucosa between BPD group and BD group (with P values above 0.05); At 24 h after injury, the SD group, SPD group, BD group, and BPD group had statistically significant differences in overall comparison of the liver, kidney, and small intestinal mucosal blood flow (F=1 347.52, 125.23, 1 210.84; with P values below 0.05). There were significant differences in blood flow of liver, kidney and small intestine mucosa between BPD group and BD group (t=89.72, 6.57, 10.23; with P values below 0.05); At 48 h after injury, the SD group, SPD group, BD group, and BPD group had statistically significant differences in overall comparison of the liver, kidney, and small intestinal mucosal blood flow (F=1 044.13, 20.69, 174.35; with P values below 0.05). There were statistically statistically significant differences in blood flow between the liver and small intestine mucosa of the BPD group and the BD group (t=51.90, 34.72; with P values below 0.05), and there was no statistically significant difference in renal blood flow (t=0.37, P>0.05); At 72 h after injury, there were statistically significant differences between the liver and kidney blood flow in the SD group, SPD group, BD group, and BPD group (F=328.27, 16.01; with P values below 0.05), there was no statistically significant difference in the small intestinal mucosa blood flow of the 4 groups (P>0.05). There was a statistically significant difference in liver blood flow between BPD group and BD group (t=25.32, P<0.05) and no statistically significant difference in kindey blood flow (P> 0.05). (2)Immediately after the injury and 48 h after the injury, there were no statistically significant difference in the overall pH between the 4 groups (with P values above 0.05); at 6, 24 h, and 72 h after injury, the differences of pH between the 4 groups were statistically significant (F=54.48, 5.68, 1.98; with P values below 0.05), and at 6 and 24 h after injury, there were statistically significant differences in pH between the BPD group and the BD group (t= 5.32, 3.51; with P values below 0.05), at 72 h after injury, there was no statistically statistically significant difference in pH between the two groups (P>0.05). Immediately after the injury and at 6, 24 h after injury, the overall comparison between the 4 groups of oxygen partial pressure groups were statistically significant (F=26.55, 16.34, 2.37; with P values below 0.05). There was no statistically significant difference in oxygen partial pressure between the BPD group and the BD group immediately after injury (P>0.05), and the differences between the two groups were statistically significant at 6 and 24 h after injury (t=4.58, 0.62; with P values below 0.05). At 48 and 72 h after injury, there were no statistically significant differences in the overall comparison between the 4 groups of blood lactic acid groups (with P values above 0.05). Immediately after injury, and at 6, 24 h after injury, the overall comparison between the 4 groups were statistically significant (F=3.12, 61.67, 50.83; with P values below 0.05). There was no statistically significant difference in oxygen partial pressure between the BPD group and the BD group immediately after injury (P> 0.05), and the difference between the two groups were statistically significant at 6 and 24 h after injury (t=6.98, 3.56; with P values below 0.05). The results of experiment two showed: (1) Immediately after injury and 72 h after injury, there were no significant differences in the overall comparison of MAP among the 4 groups (with P values above 0.05). At 6, 24, and 48 h after injury, the overall comparison of MAP between the 4 groups were statistically significant (F=292.73, 104.29, 5.01; with P values below 0.05), and the differences in MAP between the BPD group and the BP group were statistically significant (t=6.02, 6.70, 1.24; with P values below 0.05). (2) At 72 h after injury, the survival rates of the BPD group and the BD group were 70% and 50%, respectively. The difference between the 2 groups was statistically significant (χ²=11.03, P<0.05).

Sodium valproate combines with delayed fluid replacement can significantly increase the perfusion of liver, kidney and intestinal mucosa blood in severe burn-blast combined injury rats, maintain stable blood pressure early after injury, reduce blood lactate levels, and improve the survival rate 72 h after injury.