泛醇-谷氨酰胺对烧伤大鼠肠道的影响及其量效关系

Effects of panthenol-glutamine on intestine of rats with burn injury and its dose-effect relationship

目的研究泛醇与谷氨酰胺对烧伤大鼠肠道损伤和运动功能的影响及其量效关系。方法（1）拆方实验。将90只SD大鼠按随机数字表法分为A—I组，每组lO只。将各组大鼠制成30％TBSAⅢ度烧伤模型，伤后4h开始灌胃泛醇和谷氨酰胺，剂量分别为1．00、4，0．50、4，0．25、4，1．00、2，0．50、2，0．25、2，1．00、I，0．50、I，0．25、lg·kg-1·d-1，每日剂量分2次灌胃，连续7d。停药当天采集大鼠血液及肠道组织，观测肠道推进指数、血清二胺氧化酶（DAO）活性、全血乙酰胆碱含量、肠黏膜蛋白含量，筛选泛醇和谷氨酰胺最佳配比。（2）药效学实验。将70只SD大鼠按照随机数字表法分为正常对照组（不进行任何处理）、烧伤组、烧伤＋泛醇组、烧伤＋谷氨酰胺组、烧伤＋低剂量泛醇．谷氨酰胺（简称“泛谷”）组、烧伤＋中剂量泛谷组、烧伤＋高剂量泛谷组，每组10只。将后6组大鼠按上述模型致伤，伤后4h开始灌胃药物，烧伤＋泛醇组给予泛醇1．00g·kg-1·d-1；烧伤＋谷氨酰胺组给予谷氨酰胺4g·kg-1·d-1；烧伤＋低、中、高剂量泛谷组给予泛醇和谷氨酰胺，剂量分别为0．50、2，1．00、4，2．00、8g·kg-1·d-1，每日剂量分2次灌胃，连续7d。检测指标及时问同拆方实验，另外增加各烧伤组大鼠肠道病理学观察；正常对照组行相同检测。对数据行析因设计方差分析、单因素方差分析及Fisher确切概率法检验，两两比较行LSD检验。结果（1）A、B组大鼠肠道推进指数、肠黏膜蛋白含量相近（P值均大于0．05），显著高于其余7组（P值均小于0．01）；A组大鼠乙酰胆碱含量显著高于其余8组（P值均小于0．01）；A、D、E组大鼠DAO活性相近（P值均大于0．05），低于其余6组（P值均小于0．01）。泛醇与谷氨酰胺最佳配比剂量为1．00、4g·kg-1·d-1。（2）与正常对照组比较，烧伤组大鼠肠道推进指数、乙酰胆碱和肠黏膜蛋白含量明显降低，DAO含量明显增高（P值均小于0．01）；烧伤＋泛醇组大鼠肠道推进指数明显降低（P〈0．01）；烧伤＋谷氨酰胺组大鼠肠道推进指数、乙酰胆碱含量明显降低（P值均小于0．01）；烧伤＋低剂量泛谷组大鼠肠道推进指数明显降低（P〈0．01）；烧伤＋中、高剂量泛谷组大鼠4项指标水平未见明显改变（P值均大于0．05）。与烧伤组[0．50±0．07、（69±10）IXg／mL、（26±l】）汕g／g、（0．672±0．145）U／mL]比较，烧伤＋泛醇组大鼠乙酰胆碱和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）；烧伤＋谷氨酰胺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）；烧伤＋低剂量泛谷组乙酰胆碱、肠黏膜蛋白含量升高（P值均小于0．01）；烧伤＋中、高剂量泛谷组肠道推进指数、乙酰胆碱和肠黏膜蛋白含量升高，DAO活性降低[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，P值均小于0．01]。烧伤＋中、高剂量泛谷组4项指标水平相近或相同（P值均大于0．05）。与烧伤组比较，烧伤＋泛醇组绒毛排列紊乱鼠数显著减少（P〈0．05）；烧伤＋谷氨酰胺组绒毛高度下降、排列紊乱和中性粒细胞浸润鼠数明显减少（P值均小于0．05）；烧伤＋低剂量泛谷组绒毛高度下降、排列紊乱及细胞变性坏死和中性粒细胞浸润鼠数显著减少（P值均小于0．05）；烧伤＋中、高剂量泛谷组绒毛高度下降、数量减少、排列紊乱及细胞变性坏死和中性粒细胞浸润鼠数显著减少（P值均小于0．05）。烧伤＋中、高剂量泛谷组各项指标鼠数接近（P值均大于0．05）。结论联合应用泛醇与谷氨酰胺能明显减轻烧伤大鼠肠黏膜损伤并促进胃肠运动，疗效优于单一用药，二者最佳配比剂量为1．00、4g·kg-1·d-1。

Objective To study the effects of the panthenol-glutamine on intestinal damage and mo- tor function of intestine in rats with burn injury as well as its dose-effect relationship. Methods （ 1 ） Ex- periment 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 and4, 1.00 and2, 0.50 and2, 0.25 and2, 1.00 and 1, 0.50 and 1, 0.25 and 1 g kg-l 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 aeetylcholine 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 ＋ pantheno! （ 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 - d - 1, rats in group B ＋ G with glutamine for 4 g kg - d - , 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 - l . 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 patholog- ical change in intestine was observed. The same process was carried out in the rats of group NC. Data were processed with factoria! designed analysis of variance （ANOVA）, one-way ANOVA and Fisher＇s exact prob- ability test. LSD was applied for paired comparison. Results （ 1 ） The values of intestinal propulsion in- dex 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 O. O1 ）. Content of acetyl- choline in group A was significantly higher than that of the other 8 groups （ with P values all below 0. O1 ）. DAO activity in groups A, D, and E was close in value （ with P values all above O. 05 ）, and all of the values were significantly lower than those of the other 6 groups （ with P values all below O. O1 ）. The best proportion of panthenol and glutamine was 1. O0 and 4 g kg- 1 . d - 1. （2） Compared with those of group NC, the in- testinal propulsion index, the contents of acetylcholine and intestinal mucosa protein were decreased signifi- cantly, 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 in- testinal 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, （6910） Ig/mL, （2611） ig/g, （0.672 0.145） U/mL], the contents of acetylcho- line 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 acetyl- choline 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 in- creased significantly, while the DAO activity obviously decreased in groups B ＋ MPG and B ＋ HPG [0.66 0.07, 0.680.05; （i63-S24）,＂ （168 15） Ig/mL; （57 7）, （57 7） Ig/g; （0.203 0.070）, （0. 193 O. 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 〈 O. 05 ） ; the numbers of rats with villi decreased in height, irregularly arranged villi, and neutrophil infiltra- tion 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 infil- tration in group B ＋ LPG Were decreased significantly （ with P values all below 0.05 ） ; the numbers of rats with villi decreased in heigh! 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 ）. Conclusions 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.