基于肠-脉络丛血管屏障探讨桃核承气汤对脓毒性脑病的治疗作用  

Discussion on therapeutic effect of Taohe Chengqi Decoction on sepsis-associated encephalopathy based on the gut-choroid plexus vascular barrier

作　　者：燕晓茹 易亮[1] 李洁[1] 刘佳妮[1] 付妍 茹江丽 黄烨[1] 杨志旭[1] 陈恂 陈姝[1] YAN Xiaoru;YI Liang;LI Jie;LIU Jiani;FU Yan;RU Jiangli;HUANG Ye;YANG Zhixu;CHEN Xun;CHEN Shu(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院,北京100091

出　　处：《中华中医药杂志》2024年第10期5488-5492,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.82204913);中国中医科学院优秀青年科技人才培养专项(No.ZZ16-YQ-012)。

摘　　要：目的:探讨桃核承气汤对脓毒性脑病(SAE)的治疗效果及作用机制。方法:70只雄性SD大鼠随机分为假手术组,模型组,0.5倍、1倍、2倍桃核承气汤组。采用盲肠结扎法(CLP)构建模型。采用旷场实验观测各组大鼠运动及探索能力;ELISA法检测大鼠血清及海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6和脂多糖(LPS)的含量;尼氏染色法观察海马组织中尼氏小体的形成;免疫荧光法检测肠、脉络丛组织切片中PV-1的表达;Western Blot法检测肠、脉络丛组织中PV-1、HIF-1α、VEGF-A的蛋白表达。结果:与假手术组比较,CLP术后24 h模型组腹腔感染明显、大鼠运动能力明显下降,血清和海马组织中炎症因子TNF-α、IL-1β、IL-6、LPS释放显著增加(P<0.01,P<0.05),肠、脉络丛组织中PV-1、HIF-1α、VEGF-A蛋白表达显著升高(P<0.01)。与模型组比较,不同浓度桃核承气汤均能改善大鼠腹腔感染情况,增加运动及探索能力,改善海马神经元损伤,显著降低血清及海马组织中TNF-α、IL-1β、IL-6、LPS的含量,其中1倍剂量效果最佳。此外,桃核承气汤能够显著降低模型组肠、脉络丛组织中PV-1、HIF-1α、VEGF-A蛋白表达(P<0.05,P<0.01)。结论:桃核承气汤能够通过改善肠-脉络丛血管屏障功能治疗SAE,而HIF-1α、VEGF-A很可能为关键调控分子。Objective:To investigate the therapeutic effect and mechanism of Taohe Chengqi Decoction on sepsis associated encephalopathy(SAE).Methods:Seventy male SD rats were randomly divided into sham group,model group,0.5 times,1 times,2 times Taohe Chengqi Decoction group.Cecal ligation and puncture(CLP)method was used to construct the model.Open field experiment was used to observe the movement and exploration ability.The contents of TNF-α,IL-1β,IL-6 and LPS in serum and hippocampal tissue were determined by ELISA.The formation of Nissl bodies in hippocampus was observed by Nissl staining.The expression of PV-1 in intestinal and choroid plexus tissues were detected by immunofluorescence method.The expressions of PV-1,HIF-1αand VEGF-A in intestinal and choroid plexus tissues were detected by Western Blot.Results:Compared with the sham operation group,intraperitoneal infection,and the locomotor ability of rats was decreased obviously,inflammatory factors TNF-α,IL-1β,IL-6,LPS release in serum and hippocampal tissue were increased in model group(P<0.01,P<0.05),the expression of PV-1,HIF-1αand VEGF-A in the intestine and choroid plexus tissues increased(P<0.01).Compared with model group,different concentrations of Taohe Chengqi Decoction could alleviate the abdominal infection,increase the locomotor and exploration ability,improve hippocampal neuron damage,and reduce the contents of TNF-α,IL-1β,IL-6 and LPS in serum and hippocampal tissue,among which the 1 times effect was the best.In addition,Taohe Chengqi Decoction could reduce the expression of PV-1,HIF-1αand VEGF-A in the intestine and choroid plexus tissues(P<0.05,P<0.01).Conclusion:Taohe Chengqi Decoction could treat SAE by improving the function of the gut-choroid plexus vascular barrier,and HIF-1αand VEGF-A may be the key regulatory molecules.

关 键 词：脓毒性脑病 桃核承气汤 肠-脑轴 肠-脉络丛血管屏障 炎症 

分 类 号：R285.5[医药卫生—中药学]