口服丙酮酸钙盐糖液对重度烧伤大鼠伤后早期氧合脏器功能及生存率的影响

Effects of calcium pyruvate oral rehydration solution on early oxygenation, organ function and survival rate in severely burned rats

  • 摘要:
      背景   近年来研究表明采用丙酮酸盐救治烧伤导致的低血容量休克疗效较好,但目前研究最多的丙酮酸钠口服安全性低,难以应用于临床。而丙酮酸钙的食字号产品已上市,食用安全性高,将其应用于口服液体复苏具有广阔前景。目前国内外尚无丙酮酸钙用于抗休克的相关研究,本实验将丙酮酸钙引入经典的WHO口服补液盐Ⅲ中,拟评价其在院前急救阶段复苏中的应用价值。
      目的   探讨口服丙酮酸钙盐糖液对重度烧伤大鼠伤后早期氧合、脏器功能及生存率的影响。
      方法   实验前将WHO推荐的4包口服补液盐Ⅲ和6.8 g丙酮酸钙混合溶于1 000 mL饮用水中,溶液渗透压为290 mmol/L,预热至37℃。雄性Wistar大鼠(6~8周龄,210~230 g)210只,随机分为假伤组(Sham组,n=30)、单纯烧伤组(Burn组,n=60)、口服补液组(OR组,n=60)和腹腔补液组(PR组,n=60)。Sham组大鼠37℃水浴浸泡,其余三组大鼠94℃沸水浸泡背部12 s、腹部6 s,致50%总体表面积Ⅲ度烧伤。OR组采用灌胃输入丙酮酸钙盐糖液的方法口服补液,PR组采用腹腔注射乳酸林格液的方法腹腔补液,两组均于伤后2 min开始补液。补液量依据Parkland公式,总共补液8 h,Sham组自由饮水,Burn组不予补液,8 h后各组均自由进食水,不再补液。各组选取20只大鼠计算24 h生存率。于伤后0.5 h、4 h、8 h、24 h从各组取10只大鼠行血气分析、脏器功能指标测量、氧化应激指标测量、脏器病理检测。
      结果   OR组24 h生存率(70%)与PR组生存率(75%)均显著高于Burn组(30%)(P均<0.05);伤后4 h、8 h、24 h,OR组和PR组各项指标较Burn组得到明显改善,且在伤后8 h、24 h,OR组血乳酸、AST、总抗氧化能力较PR组也得到显著改善(P均<0.05)。
      结论   丙酮酸钙盐糖液可改善重度烧伤大鼠伤后的缺血缺氧状态,改善氧合状况并保护脏器功能,提高机体的抗氧化能力,提高重度烧伤大鼠24 h生存率,口服丙酮酸钙盐糖液与腹腔补充乳酸盐林格液的复苏效果相近。

     

    Abstract:
      Background   Recent studies have shown that pyruvate is effective in treating hypovolemic shock caused by burn. However, the safety of oral administration of sodium pyruvate, which is the most studied at present, is low, which makes it difficult for its oral preparation to be applied in clinical practice. However, the food-grade product of calcium pyruvate has been put on the market with high edible safety, so it has broad prospects in oral liquid resuscitation. At present, there is no relevant research on calcium pyruvate for anti-shock at home and abroad. In this experiment, calcium pyruvate is introduced into the classic WHO oral rehydration salt Ⅲ, and its value in resuscitation in pre-hospital emergency stage is evaluated.
      Objective   To investigate the effects of calcium pyruvate oral rehydration solution on oxygenation, organ function and survival rate of severely burned rats.
      Methods   Before the experiment, 4 packets of oral rehydration salts Ⅲ recommended by WHO and 6.8 g calcium pyruvate were mixed and dissolved in 1 000 mL drinking water. The osmotic pressure of the solution was 290 mmol/L and then preheated it to 37℃. Totally 210 male wistar rats (6-8 weeks old, 210-230 g) were included and they were randomly divided into sham injury group (Sham group, n=30), simple burn group (Burn group, n=60), oral rehydration group (OR group, n=60) and intraperitoneal rehydration group (PR group, n=60). Sham group was soaked in water at 37℃ while the other three groups were soaked in boiling water at 94℃ for 12 seconds on their back and 6 seconds on their abdomen, which were inflicted with 50% total body surface area full-thickness scald on the back and abdomen. The OR group received calcium pyruvate oral solution while the PR group received lactate ringer’s solution. Both groups started rehydration at 2 minutes after injury. The rehydration volume was based on Parkland formula. Total rehydration time was 8 h. The Sham group drank water freely while the Burn group did not receive rehydration. After 8 h, all groups drank water freely. Twenty rats in each group were selected to observe the 24-hour survival rate. At 0.5 h, 4 h, 8 h and 24 h after injury, 10 rats were selected from each group to measure blood gas analysis indexes, organ function indexes, oxidative stress indexes and histopathological changes.
      Results   The 24-hour survival rates of the OR group and PR group were significantly higher than that of the Burn group (70%, 75% vs 30%) (P<0.05); At 4 h, 8 h and 24 h after injury, the indexes and histopathology of the OR and the PR groups were significantly improved compared with those of the Burn group; and at 8 h and 24 h after injury, Lac, AST and T-AOC in the OR group were significantly improved compared with those of the PR group (P<0.05).
      Conclusion   Calcium pyruvate oral rehydration solution can improve ischemia, hypoxia, oxygenation and protect organ function, improve antioxidant capacity and 24-hour survival rate of severely burned rats. The resuscitation effect of calcium pyruvate oral rehydration solution is similar to that of intraperitoneal supplementation of Ringer's lactate solution.

     

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