凉血通瘀方对脑出血模型大鼠脑组织、肠组织、血清胆囊收缩素8的影响
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摘要
目的探讨凉血通瘀方治疗脑出血的可能机制。方法 108只SD大鼠随机分为假手术组、模型组、凉血通瘀组各36只,除假手术组外其余各组采用自体血注入法制作脑出血大鼠模型。凉血通瘀组于造模成功后按1.3 ml/100 g给予凉血通瘀方水煎剂(浓度1.2 g/ml)灌胃,每日1次,连续5日;假手术组、模型组每日灌胃同等量蒸馏水。各组于灌胃后24 h、72 h、120 h进行大鼠神经学评分,评定肠道动力功能,免疫组化法检测脑组织、肠组织胆囊收缩素8(CCK-8)表达,ELISA法检测脑组织、肠组织及血清CCK-8含量。结果与模型组同时间比较,凉血通瘀组大鼠在72 h、120 h神经学评分降低(P<0.05或P<0.01)。与假手术组比较,模型组大鼠6 h黑便粒数减少,黑便百分比降低(P<0.05或P<0.01),而凉血通瘀组大鼠黑便百分比较模型组升高(P<0.01)。与模型组同时间比较,凉血通瘀组大鼠脑组织CCK-8表达在72 h、120 h表达增强,肠组织CCK-8表达在24 h增强(P<0.05或P<0.01);凉血通瘀组大鼠血清CCK-8含量72 h较假手术组和模型组降低(P<0.01)。结论凉血通瘀方可改善脑出血大鼠神经功能缺损,增强胃肠动力,促进排便,可能与增加肠组织、脑组织CCK-8表达,降低血清CCK-8含量有关。
Objective To explore the possible mechanism of Liangxue Tongyu Recipe( 凉血通瘀方) in the treatment of cerebral hemorrhage. Methods A total of 108 SD rats were randomly divided into sham operation group,model group and Liangxue Tongyu group,with 36 rats in each group. All the rats except the sham operation group were treated with autologous blood injection to make cerebral hemorrhage rat model. After successful modeling,Liangxue Tongyu group was given 1. 3 ml/100 g Liangxue Tongyu Recipe Decoction( concentration 1. 2 g/ml),once a day for 5 days; The sham operation group and model group were given same amount of distilled water by gavage. The neurological scores and the intestinal motility of the rats were evaluated at 24 h,72 h and 120 h after intragastric administration. The expression of cholecystokinin-8( CCK-8) in brain tissue and intestinal tissue was detected by immunohistochemistry. Brain tissue,intestinal tissue and serum CCK-8 contents were detected by enzyme-linked immuno sorbent assay( ELISA). Results Compared with the model group,the neurological scores of the rats in the Liangxue Tongyu group decreased at 72 h and 120 h( P < 0. 05 or P < 0. 01). Compared with the sham operation group,the number of black stools decreased and the percentage of black stools decreased at 6 h in the model group( P < 0. 05 or P < 0. 01),while the percentage of black stool in the Liangxue Tongyu group was increased when compared with that in the model group( P < 0. 01). Compared with the model group,the expression of CCK-8 in the brain tissue of Liangxue Tongyu group increased at 72 h and 120 h,and the expression of CCK-8 in intestinal tissue increased at 24 h( P < 0. 05 or P < 0. 01). The serum CCK-8 content of the rats in the Liangxue Tongyu group was decreased when compared with that in the sham operation group and the model group( P < 0. 01). Conclusion Liangxue Tongyu Recipe can improve neurological deficits,increase gastrointestinal motility and promote defecation in rats with cerebral hemorrhage,which may be related to increasing CCK-8 expression in intestinal tissue and brain tissue and decreasing serum CCK-8 content.
Objective To explore the possible mechanism of Liangxue Tongyu Recipe( 凉血通瘀方) in the treatment of cerebral hemorrhage. Methods A total of 108 SD rats were randomly divided into sham operation group,model group and Liangxue Tongyu group,with 36 rats in each group. All the rats except the sham operation group were treated with autologous blood injection to make cerebral hemorrhage rat model. After successful modeling,Liangxue Tongyu group was given 1. 3 ml/100 g Liangxue Tongyu Recipe Decoction( concentration 1. 2 g/ml),once a day for 5 days; The sham operation group and model group were given same amount of distilled water by gavage. The neurological scores and the intestinal motility of the rats were evaluated at 24 h,72 h and 120 h after intragastric administration. The expression of cholecystokinin-8( CCK-8) in brain tissue and intestinal tissue was detected by immunohistochemistry. Brain tissue,intestinal tissue and serum CCK-8 contents were detected by enzyme-linked immuno sorbent assay( ELISA). Results Compared with the model group,the neurological scores of the rats in the Liangxue Tongyu group decreased at 72 h and 120 h( P < 0. 05 or P < 0. 01). Compared with the sham operation group,the number of black stools decreased and the percentage of black stools decreased at 6 h in the model group( P < 0. 05 or P < 0. 01),while the percentage of black stool in the Liangxue Tongyu group was increased when compared with that in the model group( P < 0. 01). Compared with the model group,the expression of CCK-8 in the brain tissue of Liangxue Tongyu group increased at 72 h and 120 h,and the expression of CCK-8 in intestinal tissue increased at 24 h( P < 0. 05 or P < 0. 01). The serum CCK-8 content of the rats in the Liangxue Tongyu group was decreased when compared with that in the sham operation group and the model group( P < 0. 01). Conclusion Liangxue Tongyu Recipe can improve neurological deficits,increase gastrointestinal motility and promote defecation in rats with cerebral hemorrhage,which may be related to increasing CCK-8 expression in intestinal tissue and brain tissue and decreasing serum CCK-8 content.
引文
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[10]吴犀翎,黄小波,陈文强,等.脑血管病急性期胃肠道系统与脑的关系探讨[J].中国中医药信息杂志,2014,21(7):1-3.
[11]MARTIN CR,OSADCHIY V,KALANI A,et al.The Brain-gut-microbiome axis[J].Cell mol gastroenterol hepatol,2018,6(2):133-148.
[12]王恒,邵恩得,张金荣,等.胆囊收缩素-8对高血压大鼠脑出血后核因子-κB活性的影响[J].河北医药,2014,36(6):812-815.
[13]WEN D,AN M,GOU H,et al.Cholecystokinin-8inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway[J].Neurotoxicology,2016,57:31-38.doi:10.1016/j.neuro.2016.08.008.
[2]HEMPHILL JC,GREENBERG SM,ANDERSON CS,et al.Guidelines for the management of spontaneous intracerebral hemorrhage:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J].Stroke,2015,46(7):2032-2060.
[3]李建香,过伟峰,傅淑平,等.基于脑肠互动探讨通腑泻热法治疗中风的机制[J].中医杂志,2018,59(4):292-294.
[4]过伟峰,张兰坤,吴勉华,等.凉血通瘀中药治疗脑出血急性期168例疗效观察[J].北京中医药大学学报,2012,35(9):603-606,619.
[5]张兰坤,过伟峰,徐丹,等.凉血通瘀方治疗出血性中风急性期瘀热阻窍证患者73例临床观察[J].中医杂志,2012,53(1):28-30,44.
[6]XUE M,DEL BIGIO MR.Intracerebral injection of autologous whole blood in rats:time course of inflammation and cell death[J].Neurosci Lett,2000,283(3):230-232.
[7]CHEN W,HU YQ,JIANG LF,et al.Mechanism of action of Zhuyu Annao pill in mice with cerebral intrahemorrhage based on TLR4[J].Asian Pac J Trop Med,2016,9(11):1095-1100.
[8]LI J,YUAN M,LIU Y,et al.Incidence of constipation in stroke patients:A systematic review and meta-analysis[J].Medicine,2017,96(25):e7225.
[9]王永炎,谢颖桢.化痰通腑法治疗中风病痰热腑实证的源流及发展(四):中风后脑肠轴改变及化痰通腑法治疗痰热腑实证的效应机理[J].北京中医药大学学报(中医临床版),2013,20(4):1-4,10.
[10]吴犀翎,黄小波,陈文强,等.脑血管病急性期胃肠道系统与脑的关系探讨[J].中国中医药信息杂志,2014,21(7):1-3.
[11]MARTIN CR,OSADCHIY V,KALANI A,et al.The Brain-gut-microbiome axis[J].Cell mol gastroenterol hepatol,2018,6(2):133-148.
[12]王恒,邵恩得,张金荣,等.胆囊收缩素-8对高血压大鼠脑出血后核因子-κB活性的影响[J].河北医药,2014,36(6):812-815.
[13]WEN D,AN M,GOU H,et al.Cholecystokinin-8inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway[J].Neurotoxicology,2016,57:31-38.doi:10.1016/j.neuro.2016.08.008.