Wang Pei, Zhao Yun, Qi Hua-bing, Yi Dong, Wang Feng-jun, Wang Shi-liang, Peng Xi
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, the Third Military Medical University, Chongqing 400038, China.
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, the Third Military Medical University, Chongqing 400038, China. Email:
Zhonghua Shao Shang Za Zhi. 2013 Aug;29(4):338-43.
To study the effects of the panthenol-glutamine on intestinal damage and motor function of intestine in rats with burn injury as well as its dose-effect relationship.
(1) Experiment 1. Ninety SD rats were divided into groups A-I according to the random number table, with 10 rats in each group. Rats in groups A-I were inflicted with 30% TBSA full-thickness burn and fed by gavage with panthenol and glutamine at post injury hour (PIH) 4, in the whole dosage of 1.00 and 4, 0.50 and 4, 0.25 and 4, 1.00 and 2, 0.50 and 2, 0.25 and 2, 1.00 and 1, 0.50 and 1, 0.25 and 1 g·kg(-1)·d(-1). The feeding was carried out twice a day to achieve the total dosage in 7 days. On drug withdrawal day, blood and intestinal tissue were harvested to detect the intestinal propulsion index, diamine oxidase (DAO) activity in serum, and the content of acetylcholine and intestinal mucosa protein. The best proportion of panthenol and glutamine was screened. (2) Experiment 2. Seventy SD rats were divided into normal control (NC), burn (B), burn+panthenol (B+P), burn+glutamine (B+G), and burn+low, moderate, or high dose of panthenol-glutamine (B+LPG, B+MPG, B+HPG) groups according to the random number table, with 10 rats in each group. Rats in the latter 6 groups were inflicted with 30% TBSA full-thickness burn. Rats in the latter 5 groups were fed by gavage with panthenol and (or) glutamine at PIH 4. Rats in group B+P were fed with panthenol for 1 g·kg(-1)·d(-1), rats in group B+G with glutamine for 4 g·kg(-1)·d(-1), rats in groups B+LPG, B+MPG, and B+HPG with panthenol and glutamine in the dosage of 0.50 and 2, 1.00 and 4, 2.00 and 8 g·kg(-1)·d(-1). The feeding was carried out twice a day to achieve the total dosage for 7 days. The indexes and time point for observation were the same as those of experiment 1. Meanwhile, the pathological change in intestine was observed. The same process was carried out in the rats of group NC. Data were processed with factorial designed analysis of variance (ANOVA), one-way ANOVA and Fisher's exact probability test. LSD was applied for paired comparison.
(1) The values of intestinal propulsion index and intestinal mucosa protein content in groups A and B were close (with P values all above 0.05), and were significantly higher than those of the other 7 groups (with P values all below 0.01). Content of acetylcholine in group A was significantly higher than that of the other 8 groups (with P values all below 0.01). DAO activity in groups A, D, and E was close in value (with P values all above 0.05), and all of the values were significantly lower than those of the other 6 groups (with P values all below 0.01). The best proportion of panthenol and glutamine was 1.00 and 4 g·kg(-1)·d(-1). (2) Compared with those of group NC, the intestinal propulsion index, the contents of acetylcholine and intestinal mucosa protein were decreased significantly, while the DAO activity obviously increased in group B (with P values all below 0.01); the intestinal propulsion index was decreased significantly in group B+P (P < 0.01); the intestinal propulsion index and content of acetylcholine were decreased significantly in group B+G (with P values all below 0.01); the intestinal propulsion index was decreased significantly in group B+LPG (P < 0.01); no obvious change was observed in groups B+MPG and B+HPG (with P values all above 0.05). Compared with those of group B [0.50 ± 0.07, (69 ± 10) µg/mL, (26 ± 11) µg/g, (0.672 ± 0.145) U/mL], the contents of acetylcholine and intestinal mucosa protein were increased significantly, DAO activity decreased significantly in group B+P (with P values all below 0.01); the contents of intestinal mucosa protein was increased significantly, DAO activity decreased significantly in group B+G (with P values all below 0.01); the contents of acetylcholine and intestinal mucosa protein were increased significantly in group B+LPG (with P values all below 0.01); the intestinal propulsion index, the contents of acetylcholine and intestinal mucosa protein were increased significantly, while the DAO activity obviously decreased in groups B+MPG and B+HPG [0.66 ± 0.07, 0.68 ± 0.05; (163 ± 24), (168 ± 15) µg/mL; (57 ± 7), (57 ± 7) µg/g; (0.203 ± 0.070), (0.193 ± 0.068) U/mL, with P values all below 0.01]. The levels of the four indexes in groups B+MPG and B+HPG were close or the same in values (with P values all above 0.05). Compared with those of group B, the numbers of rats with irregularly arranged villi in group B+P were decreased significantly (P < 0.05); the numbers of rats with villi decreased in height, irregularly arranged villi, and neutrophil infiltration in group B+G were decreased significantly (with P values all below 0.05); the numbers of rats with villi decreased in height, irregularly arranged villi, degeneration and necrosis of cells, and neutrophil infiltration in group B+LPG were decreased significantly (with P values all below 0.05); the numbers of rats with villi decreased in height and number, irregularly arranged villi, degeneration and necrosis of cells, and neutrophil infiltration in groups B+MPG and B+HPG were decreased significantly (with P values all below 0.05). There was no statistically significant difference between group B+HPG and group B+MPG for the former mentioned five indexes (with P values all above 0.05).
Combined application of panthenol and glutamine can obviously reduce intestinal mucosa damage and promote gastrointestinal motility of rats with burn injury, and they show curative effect superior to exclusive use of either of the two drugs. The best proportion of panthenol and glutamine is 1.00 and 4 g·kg(-1)·d(-1).
研究泛醇 - 谷氨酰胺对烧伤大鼠肠道损伤及肠动力功能的影响及其量效关系。
(1)实验1。将90只SD大鼠按随机数字表分为A - I组,每组10只。A - I组大鼠均造成30%总体表面积的全层烧伤,于伤后4小时开始经口灌胃给予泛醇和谷氨酰胺,全量分别为1.00与4、0.50与4、0.25与4、1.00与2、0.50与2、0.25与2、1.00与1、0.50与1、0.25与1 g·kg⁻¹·d⁻¹。每日灌胃2次,7天达到总量。停药日采集血液和肠组织,检测肠推进指数、血清二胺氧化酶(DAO)活性、乙酰胆碱含量及肠黏膜蛋白含量。筛选出泛醇与谷氨酰胺的最佳配比。(2)实验2。将70只SD大鼠按随机数字表分为正常对照组(NC)、烧伤组(B)、烧伤 + 泛醇组(B + P)、烧伤 + 谷氨酰胺组(B + G)、烧伤 + 低、中、高剂量泛醇 - 谷氨酰胺组(B + LPG、B + MPG、B + HPG),每组10只。后6组大鼠均造成30%总体表面积的全层烧伤。后5组大鼠于伤后4小时开始经口灌胃给予泛醇和(或)谷氨酰胺。B + P组给予泛醇1 g·kg⁻¹·d⁻¹,B + G组给予谷氨酰胺4 g·kg⁻¹·d⁻¹,B + LPG、B + MPG、B + HPG组给予泛醇和谷氨酰胺的剂量分别为0.50与2、1.00与4、2.00与8 g·kg⁻¹·d⁻¹。每日灌胃2次,7天达到总量。观察指标及时间点同实验1。同时观察肠道病理变化。NC组大鼠进行同样操作。数据采用析因设计方差分析、单因素方差分析及Fisher确切概率检验处理。采用LSD进行两两比较。
(1)A组和B组的肠推进指数及肠黏膜蛋白含量值相近(P值均大于0.05),且均显著高于其他7组(P值均小于0.01)。A组乙酰胆碱含量显著高于其他8组(P值均小于0.01)。A、D、E组DAO活性值相近(P值均大于0.05),且均显著低于其他6组(P值均小于0.01)。泛醇与谷氨酰胺的最佳配比为1.00与4 g·kg⁻¹·d⁻¹。(2)与NC组比较,B组肠推进指数、乙酰胆碱及肠黏膜蛋白含量显著降低,而DAO活性明显升高(P值均小于0.01);B + P组肠推进指数显著降低(P < 0.01);B + G组肠推进指数及乙酰胆碱含量显著降低(P值均小于0.01);B + LPG组肠推进指数显著降低(P < 0.01);B + MPG和B + HPG组无明显变化(P值均大于0.05)。与B组[0.50 ± 0.07,(69 ± 10) μg/mL,(26 ± 11) μg/g,(0.672 ± 0.145) U/mL]比较,B + P组乙酰胆碱及肠黏膜蛋白含量显著升高,DAO活性显著降低(P值均小于0.01);B + G组肠黏膜蛋白含量显著升高,DAO活性显著降低(P值均小于0.01);B + LPG组乙酰胆碱及肠黏膜蛋白含量显著升高(P值均小于0.01);B + MPG和B + HPG组肠推进指数、乙酰胆碱及肠黏膜蛋白含量显著升高,而DAO活性明显降低[0.66 ± 0.07,0.68 ± 0.05;(163 ± 2)4,(168 ± 15) μg/mL;(57 ± 7),(57 ± 7) μg/g;(0.203 ± 0.070),(0.193 ± 0.068) U/mL,P值均小于0.01]。B + MPG和B + HPG组上述4项指标水平相近或相同(P值均大于0.05)。与B组比较,B + P组绒毛排列不规则的大鼠数量显著减少(P < 0.05);B + G组绒毛高度降低、绒毛排列不规则及中性粒细胞浸润的大鼠数量显著减少(P值均小于0.05);B + LPG组绒毛高度降低、绒毛排列不规则、细胞变性坏死及中性粒细胞浸润的大鼠数量显著减少(P值均小于0.05);B + MPG和B + HPG组绒毛高度及数量降低、绒毛排列不规则、细胞变性坏死及中性粒细胞浸润的大鼠数量显著减少(P值均小于0.05)。B + HPG组与B + MPG组上述5项指标比较差异无统计学意义(P值均大于0.05)。
泛醇与谷氨酰胺联合应用可明显减轻烧伤大鼠肠黏膜损伤,促进胃肠动力,且疗效优于单独使用其中任何一种药物。泛醇与谷氨酰胺的最佳配比为1.00与4 g·kg⁻¹·d⁻¹。