中药抗休克合剂对严重烫伤大鼠早期肠损伤的影响

【摘要】 目的 观察在高渗盐溶液 (HS) 补液基础上应用中药抗休克合剂对严重烫伤大鼠早期肠损伤的影响。方法 选取 32 只 8 周龄 SD 大鼠, 按照随机数表法将其随机分为假伤组、LR 组、HS600 组、HS600+中药组,每组 8 只。假伤组大鼠建立假伤模型以及 LR 组、HS600 组、HS600+中药组大鼠建立烫伤模型后, LR 组大鼠采用乳酸钠林格注射液 (LR) 补液, HS600 组大鼠采用 600 mmol / L HS 补液, HS600+中药组大鼠采用 600 mmol / LHS 补液+中药抗休克合剂灌胃。对比观察模型建立 24 h 后各组大鼠血 Na+浓度, 血清炎症因子水平以及小肠组织氧化应激水平与 p38 丝裂原活化蛋白激酶 (p38MAPK) 通路活化程度。结果 LR 组大鼠血 Na+浓度明显低于假伤组、HS600 组及 HS600+中药组 (q = 14.910、32.211、30.010, P 均<0.001), 且 HS600 组与 HS600+中药组无明显差异 (q = 2.198, P= 0.130)。LR 组、HS600 组及 HS600+中药组大鼠血清肿瘤坏死因子-α、白细胞介素-10、白细胞介素-18 水平以及小肠组织中丙二醛水平和磷酸化 p38MAPK 与 p38MAPK 比值均明显高于假伤组 (肿瘤坏死因子-α: q = 16.070、10.810、7.579, P 均<0.001; 白细胞介素-10: q = 15.920、20.210、23.850, P 均<0.001;白细胞介素-18: q = 12.750、7.562、3.897, P < 0.001、P < 0.001、P = 0.049; 丙二醛: q = 28.450、20.320、10.160, P 均<0.001; 磷酸化 p38MAPK 与 p38MAPK 比值: q = 54.310、15.090、9.196, P 均<0.001), 且 HS600+中药组大鼠血清肿瘤坏死因子-α 与白细胞介素-18 水平以及小肠组织中丙二醛水平和磷酸化 p38MAPK 与p38MAPK 比值均明显低于 LR 组与 HS600 组、白细胞介素-10 水平明显高于 LR 组与 HS600 组 (肿瘤坏死因子-α:q = 8.494、3.932, P<0.001、P = 0.048; 白细胞介素-18: q = 9.357、4.165, P<0.001、P = 0.031; 丙二醛: q =18.290、10.160, P 均<0.001; 磷酸化 p38MAPK 与 p38MAPK 比值: q = 45.110、5.899, P<0.001、P= 0.001; 白细胞介素-10: q = 7.929、3.939, P<0.001、P= 0.047)。LR 组、HS600 组及 HS600+中药组大鼠小肠组织中超氧化物歧化酶水平均明显低于假伤组 (q = 20.880、14.120、11.110, P 均<0.001), 且 HS600+中药组明显高于 LR组与 HS600 组 (q = 9.772、4.008, P<0.001、P= 0.043)。结论 与单独应用 LR 或 HS 补液相比, 在 HS 补液基础上加用中药抗休克合剂可有效降低严重烫伤大鼠机体炎症反应及氧化应激反应程度、抑制 p38MAPK 通路过度活化, 从而减轻早期肠损伤。

Effect of Chinese Medicine Anti-shock Mixture on Early Intestinal Injury of Rats with Severe Scalds

【Abstract】 Objective To observe the effect of Chinese medicine anti-shock mixture on early intestinal injury of rats with severe scalds on the basis of fluid replacement with hypertonic salt solution (HS). Methods Thirty-two 8-week SD rats were divided, using the random number table, into the sham group ( n = 8), the LR group ( n = 8), the HS600 group (n = 8), and the HS600 + Chinese medicine group ( n = 8). Rats in the sham group were made sham scald model, and rats in the LR group, the HS600 group, and the HS600 + Chinese medicine group were made scald model. And then, the rats in the LR group were given fluid replacement with sodium lactate Ringer’s injection (LR), and rats in the HS600 group were given fluid replacement with 600 mmol / L HS, while rats in the HS600 + Chinese medicine group were given fluid replacement with 600 mmol / L HS plus intragastric injection of Chinese medicine anti-shock mixture. The blood Na+ concentration, the levels of serum inflammatory factors, oxidative stress levels in small intestine tissues, and the activation of p38 mitogen-activated protein kinase ( p38MAPK) pathway were compared among the four groups 24 hours after model establishment. Results The blood Na+ concentration was significantly lower in the LR group respectively compared with thesham group, the HS600 group, and the HS600 + Chinese medicine group ( q = 14.910, 32.211 and 30.010, all P < 0.001), and there was no significant difference between the HS600 group and the HS600 + Chinese medicine group in this regard ( q = 2.198, P = 0.130). The levels of serum tumor necrosis factor-α ( TNF-α), interleukin-10 ( IL-10), and interleukin-18 ( IL-18 ), malondialdehyde ( MDA) levels in small intestinal tissues and phosphorylated-p38MAPK(p-p38MAPK) / p38MAPK ratio were all obviously higher in the LR group, the HS600 group and the HS600 + Chinese medicine group compared with the sham group (TNF-α: q = 16.070, 10.810 and 7.579, all P<0.001; IL-10: q = 15.920, 20.210 and 23.850, all P<0.001; IL-18: q = 12.750, 7.562 and 3.897, P<0.001, P<0.001, P = 0.049; MDA: q = 28.450, 20.320 and 10.160, all P < 0.001; p-p38MAPK/ p38MAPK ratio: q = 54.310, 15.090 and 9.196, all P < 0.001). Moreover, the levels of serum TNF-α and IL-18, MDA levels in small intestinal tissues, and p-p38MAPK/ p38MAPK ratio were all significantly lower in the LR + Chinese medicine group respectively compared with the LR group and the HS600 group, while the levels of IL-10 were significantly higher in the LR + Chinese medicine group respectively compared with the LR group and the HS600 group (TNF-α: q = 8.494 and 3.932, P<0.001, P= 0.048; IL-18: q = 9.357 and 4.165, P< 0.001, P = 0.031; MDA: q = 18.290 and 10.160, both P< 0.001; p-p38MAPK/ p38MAPK ratio: q = 45.110 and 5.899, P<0.001, P= 0.001; IL-10: q = 7.929 and 3.939, P<0.001, P = 0.047). The levels of superoxide dismutase in small intestinal tissues of rats were all significantly lower in the LR group, the HS600 group and the HS600 + Chinese medicine group compared with the sham group ( q = 20.880, 14.120 and 11.110, all P< 0.001), while it was higher in the HS600 + Chinese medicine group than in the LR group and the HS600 group ( q = 9.772 and 4.008, P< 0.001, P= 0.043). Conclusion Compared with the simple application of fluid replacement with LR or HS, the combined application of Chinese medicine anti-shock mixture and fluid replacement with HS can significantly alleviate the early intestinal injury by decreasing the inflammatory responses and oxidative stress degree, and inhibiting the excessive activation of p38MAPK pathway.