扶正祛瘀通下法对多器官功能障碍综合征大鼠肠机械屏障功能的保护及机制
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摘要
目的:探讨扶正祛瘀通下法(参附桃红承气汤为方)对多器官功能障碍综合征(MODS)大鼠小肠黏膜损伤的保护作用及其机制。方法:健康清洁级Wistar大鼠50只,随机分为5组:对照组(10只),MODS模型组(10只),中药防治组(分低、中、高剂量3组各10只)。腹腔注射LPS造模24 h后,各组大鼠处死迅速取小肠组织,制作石蜡切片、电镜标本,观察小肠黏膜损伤程度、绒毛变化,留取部分石蜡切片标本用于免疫组织化学染色,观察小肠组织内C-kit和神经递质一氧化氮(NO)、血管活性肠肽(VIP)、P物质(SP)、乙酰胆碱(ACh)的阳性表达。结果:与对照组相比,模型组小肠黏膜充血坏死明显,小肠绒毛大部分脱落、断裂;低、中、高剂量中药防治组小肠组织损伤减轻,尤以高剂量中药防治组为著;模型组与对照组相较,小肠C-kit的细胞数量、抑制性神经递质NO、VIP的表达明显减少,兴奋性神经递质SP、ACh的表达明显增加,低、中剂量中药防治组较模型组无显著差异,高剂量中药防治组的小肠组织间C-kit细胞数量、抑制性神经递质NO、VIP表达较模型组多,但较对照组少,兴奋性神经递质SP、ACh表达较模型组少,但较对照组多。结论:(1)扶正祛瘀通下法可以有效地减轻MODS大鼠小肠黏膜的损伤,防止肠道机械屏障功能进一步被破坏。(2)扶正祛瘀通下法可以有效增加小肠C-kit、NO、VIP的分布,减少SP、ACh的分布,缓解小肠炎性反应,改善小肠蠕动功能,从而达到保护肠屏障功能。(3)扶正祛瘀通下法可通过保护肠屏障功能达到MODS的防治作用。
Objective: To investigate the protective effect of strengthening vital Qi and resolving blood stasis and purging treatment(Shenfu Taohong Chengqi Decoction) on intestinal mucosal mechanical barrier in rats with multiple organ dysfunction syndrome(MODS) and its mechanisms.Methods: Fifty healthy clean Wistar rats were randomly assigned into five groups: control group,MODS model group,traditional Chinese medicine low-dose group,middle-dose group and high-dose group with 10 rats in each group.After intraperitoneal administration of LPS for 24 h,all rats were sacrificed and intestinal tissue was removed quickly for further preparation of paraffin section and specimen of electron microscope.Injury degree of small intestinal mucosa and changes with villi were examined and immunohistochemistry was performed to detect the positive expression of C-kit,nitric oxide(NO),vasoactive intestinal peptide(VIP),P substance(SP) and andacetyl choline(ACH) in small intestine tissue.Results: Compared to control group,obvious hyperaemia and necrosis were found in the small intestinal mucosal and villi were seen to fall off and rupture from small intestinal in model group.Injury in small intestine tissue was relieved in all treatment group especially in high-dose group.In comparison with control group,number of cells expressing C-kit in small intestine and expression of inhibitory neurotransmitter NO and VIP decreased significantly and expression of excitatory neurotransmitter SP and ACh increased significantly in model group.There was no significant difference among low-dose,middle-dose treatment group and model group.Number ofcells expressing C-kit in small intestine and expression of inhibitory neurotransmitter NO and VIP in high-dose treatment were greater than those in model group,and less than those in control group.Expression of excitatory neurotransmitter SP and ACh in high-dose treatment were less than those in model group,and higher than those in control group.Conclusion:(1)Strengthening vital Qi and resolving blood stasis and purging treatment could effectively alleviate the injury in small intestine tissue and prevent the mechanical barrier function from damage of small intestinal mucosa in rats with MODS.(2)Strengthening vital Qi and resolving blood stasis and purging treatment may effectively increase the expressions of C-kit,NO,VIP and decrease the expressions of SP and ACh.Meanwhile,the inflammatory response was improved and peristalsis function of small intestinal was improved so that strengthening vital Qi and resolving blood stasis and purging treatment could protect the intestinal barrier function.(3)strengthening vital Qi and resolving blood stasis and purging treatment has preventive and therapeutic effects on MODS through protecting intestinal barrier function.
Objective: To investigate the protective effect of strengthening vital Qi and resolving blood stasis and purging treatment(Shenfu Taohong Chengqi Decoction) on intestinal mucosal mechanical barrier in rats with multiple organ dysfunction syndrome(MODS) and its mechanisms.Methods: Fifty healthy clean Wistar rats were randomly assigned into five groups: control group,MODS model group,traditional Chinese medicine low-dose group,middle-dose group and high-dose group with 10 rats in each group.After intraperitoneal administration of LPS for 24 h,all rats were sacrificed and intestinal tissue was removed quickly for further preparation of paraffin section and specimen of electron microscope.Injury degree of small intestinal mucosa and changes with villi were examined and immunohistochemistry was performed to detect the positive expression of C-kit,nitric oxide(NO),vasoactive intestinal peptide(VIP),P substance(SP) and andacetyl choline(ACH) in small intestine tissue.Results: Compared to control group,obvious hyperaemia and necrosis were found in the small intestinal mucosal and villi were seen to fall off and rupture from small intestinal in model group.Injury in small intestine tissue was relieved in all treatment group especially in high-dose group.In comparison with control group,number of cells expressing C-kit in small intestine and expression of inhibitory neurotransmitter NO and VIP decreased significantly and expression of excitatory neurotransmitter SP and ACh increased significantly in model group.There was no significant difference among low-dose,middle-dose treatment group and model group.Number ofcells expressing C-kit in small intestine and expression of inhibitory neurotransmitter NO and VIP in high-dose treatment were greater than those in model group,and less than those in control group.Expression of excitatory neurotransmitter SP and ACh in high-dose treatment were less than those in model group,and higher than those in control group.Conclusion:(1)Strengthening vital Qi and resolving blood stasis and purging treatment could effectively alleviate the injury in small intestine tissue and prevent the mechanical barrier function from damage of small intestinal mucosa in rats with MODS.(2)Strengthening vital Qi and resolving blood stasis and purging treatment may effectively increase the expressions of C-kit,NO,VIP and decrease the expressions of SP and ACh.Meanwhile,the inflammatory response was improved and peristalsis function of small intestinal was improved so that strengthening vital Qi and resolving blood stasis and purging treatment could protect the intestinal barrier function.(3)strengthening vital Qi and resolving blood stasis and purging treatment has preventive and therapeutic effects on MODS through protecting intestinal barrier function.
引文
[1]栾樱译,姚咏明.浅析老年多器官功能障碍综合征发病机制[J].中华老年多器官疾病杂志,2010,9(6):485-487.
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[10]王超,苏强,张淑文,等.多器官功能障碍综合征中医证型诊断标准的研究[J].北京中医,2007,26(4):201-204.
[11]徐新献,杨明清.白藜芦醇苷对MODS大鼠脏器功能的保护作用[J].中国实用神经疾病杂志,2007,10(4):19-20.
[12]曹佳,周康康.天然牛黄对MODS大鼠保护作用的实验研究[J].现代生物医学进展,2013,13(16):3041-3044.
[13]谢明征,齐清会.大承气颗粒对多器官功能障碍综合征大鼠小肠平滑肌细胞凋亡的干预作用[J].中国中西医结合杂志,2014,34(5):587-591.
[14]周江,王醒,蒋华,等.益气通瘀法对多器官功能障碍肠道屏障保护作用临床研究[J].中国中医急症,2012,21(9):1384-1386.
[15]袁梅,张国志,习瑾昆.白藜芦醇在大鼠急危重症胰腺炎并发多器官损伤中的作用[J].河北联合大学学报(医学版),2014,16(2):177-178.
[16]李泽培,邱野,彭燕.Cajal间质细胞与胃肠动力关系的研究进展[J].胃肠病学和肝病学杂志,2014,23(9):983-986.
[2]谭波,陈媛媛.大鼠MODS发病机制探讨[J].重庆医科大学学报,2007,32(10):1041-1048.
[3]赵晓丹,邓旻,陈志明,等.参附桃红承气汤对多器官功能障碍综合征模型大鼠肝肾功能及组织病理的影响[J].浙江中西医结合杂志,2015,25(6):557-559.
[4]胡森,盛志勇,周宝桐.MODS动物模型研究进展[J].中国危重病急救医学,1999,11(8):504-507.
[5]胡家昌,王瑞兰,俞康龙.MODS并发急性肾损伤相关临床因素探讨[J].临床急诊杂志,2013,14(2):49-52.
[6]黄灿,蔡卓夫.大承气汤对多器官功能障碍大鼠的器官保护作用[J].河北医学,2009,15(9):1065-1067.
[7]Padkin A,Goldfrad C,Brady AR,et al.Epidemiology of severe sepsis occurring in the first 24h in intensive care units in England,Wales,and Northern Ireland[J].Crit Care Med,2003,31(9):2332-2338.
[8]张正军,向勇,张力.大黄联合血液净化治疗马蜂蓄伤并多脏器功能障碍的疗效观察[J].中国药房,2014,25(35):3341.
[9]董军,张淑文,王宝恩.肠功能障碍与多器官功能障碍综合征[J].中国危重病急救医学,2005,17(12):764-767.
[10]王超,苏强,张淑文,等.多器官功能障碍综合征中医证型诊断标准的研究[J].北京中医,2007,26(4):201-204.
[11]徐新献,杨明清.白藜芦醇苷对MODS大鼠脏器功能的保护作用[J].中国实用神经疾病杂志,2007,10(4):19-20.
[12]曹佳,周康康.天然牛黄对MODS大鼠保护作用的实验研究[J].现代生物医学进展,2013,13(16):3041-3044.
[13]谢明征,齐清会.大承气颗粒对多器官功能障碍综合征大鼠小肠平滑肌细胞凋亡的干预作用[J].中国中西医结合杂志,2014,34(5):587-591.
[14]周江,王醒,蒋华,等.益气通瘀法对多器官功能障碍肠道屏障保护作用临床研究[J].中国中医急症,2012,21(9):1384-1386.
[15]袁梅,张国志,习瑾昆.白藜芦醇在大鼠急危重症胰腺炎并发多器官损伤中的作用[J].河北联合大学学报(医学版),2014,16(2):177-178.
[16]李泽培,邱野,彭燕.Cajal间质细胞与胃肠动力关系的研究进展[J].胃肠病学和肝病学杂志,2014,23(9):983-986.